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Transcript generated from video captions.

Hello. I’m Dr Maurie Markman, from City of Hope. I’d like to discuss a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

I thank you for your attention.

A version of this article first appeared on Medscape.com.

Transcript generated from video captions.

Hello. I’m Dr Maurie Markman, from City of Hope. I’d like to discuss a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

I thank you for your attention.

A version of this article first appeared on Medscape.com.

Transcript generated from video captions.

Hello. I’m Dr Maurie Markman, from City of Hope. I’d like to discuss a very interesting paper that appeared in Cancer, entitled, “Association of alcohol intake over the lifetime with colorectal adenoma and colorectal cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.”

This is an important paper. It is very clear, certainly to those in the public health community and cancer doctors, that there is an association with alcohol intake and the risk of cancer. However, in population-based surveys, there is a very large percentage of individuals who do not appear to see the risk of alcohol intake, particularly excessive alcohol intake, related to cancer, or an even larger segment of population simply doesn’t know. This analysis is important to help address this question.

The investigators looked at adults in the United States who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which is a very important study that had been ongoing for many years. Individuals in this study reported at several timepoints during their participation what their current and past alcohol intake was.

What these investigators found is as follows. Among the 88,092 participants, there were a total of 1679 incident colorectal cancers that developed over 20 years of follow-up. Investigators demonstrated that current drinkers with an average lifetime alcohol intake of 14 or more drinks per week, or approximately 2 drinks per day, had a higher risk of colorectal cancer with a hazard ratio of 1.25, a 25% increase, compared to those individuals who had ≤ 1 drink per week.

Very importantly, individuals were characterized by their own information that they provided as consistent heavy drinking versus light drinking. This was associated with almost a doubling of the risk of the development of colorectal cancer over that 20-year period.

Clearly, heavy drinking and higher lifetime alcohol intake is associated with an increased risk of colorectal cancer. This is relevant information for public health officials, primary care doctors, and the public in general to understand that there is a risk if you drink often, particularly heavy drinking, with increased development of cancer in general — but in this case, we’re talking specifically about colorectal cancer.

I thank you for your attention.

A version of this article first appeared on Medscape.com.

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

A version of this article first appeared on Medscape.com.

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

A version of this article first appeared on Medscape.com.

Individuals with obesity without diabetes taking GLP-1 receptor agonists (RAs) may have a reduced risk for certain cancers, a new study suggests.

The target trial emulation of more than 160,000 patients found that individuals receiving the medications had a 41% lower risk for obesity-associated cancers (OACs), with an even more substantial 68% risk reduction among men.

“If confirmed in prospective studies, GLP-1 RAs may be associated with a broader clinical profile that extends beyond obesity management to include potential effects on cancer risk,” wrote lead author A.H.-C. Hsu, of Houston Methodist Neal Cancer Center, Houston, and colleagues in Annals of Oncology.

How Are GLP-1 RAs Linked to Reduced Cancer Risk?

According to the investigators, obesity is a recognized risk factor for 13 malignancies: breast, colorectal, endometrial, kidney, pancreatic, thyroid, ovarian, esophageal, gastric, liver, and gallbladder cancers, as well as multiple myeloma and meningioma. These conditions account for about 40% of cancers diagnosed in high-income countries, with incidence rising fastest among younger adults.

Preclinical work suggests GLP-1 receptor activation can suppress proliferation in cancer cells that express the receptor, although these mechanisms remain poorly understood. Observational clinical data have linked GLP-1 RAs to lower cancer risk, mainly in people with type 2 diabetes, but it has remained unclear whether the same association would hold among patients with obesity without diabetes.

How Was the New Study Designed?

The investigators first identified 229,467 adults with obesity without diabetes or a prior OAC in the TriNetX federated database. These patients were entered into a target trial emulation framework, which uses trial-like eligibility, treatment, and follow-up rules to approximate a randomized comparison from observational data.

The population was divided into two cohorts; the first comprised patients who filled at least two prescriptions for a GLP-1 RA and the second included patients who received only diet or exercise counseling. Groups were balanced using 1:1 propensity score matching, yielding 80,899 patients per group. The mean age was 47 years, and about 72% of the population were women.

The primary outcome was the cumulative incidence of OACs over 2 years. Further analyses characterized the same outcome based on sex, BMI, race, and the two most-used drugs, semaglutide and tirzepatide.

What Were the Key Findings?

GLP-1 RA use was associated with a 41% lower incidence of OACs overall (hazard ratio [HR], 0.59). The association held across most subgroups, with a more pronounced benefit among men (HR, 0.32) compared with women (HR, 0.65).

Taking tirzepatide (HR, 0.31) was also associated with a greater risk reduction than taking semaglutide (HR, 0.80); however, the investigators encouraged a cautious interpretation of these findings because the study was not designed for a head-to-head comparison between the agents.

In contrast with the above positive findings, no significant risk reduction was observed among Black patients (HR, 0.77; 95% CI, 0.58-1.03) vs a roughly 50% risk reduction among White patients (HR, 0.54; 95% CI, 0.47-0.62).

The reason for the lack of benefit among Black patients is unclear.

Among specific OACs, greatest risk reductions were reported for multiple myeloma (HR, 0.37), pancreatic cancer (HR, 0.40), endometrial cancer (HR, 0.42), and colorectal cancer (HR, 0.49).

No significant risk reductions were observed for breast cancer, ovarian cancer, or meningioma.

What Are the Clinical Implications?

The investigators emphasized that the study, being observational, is insufficient to confirm that GLP-1 RAs prevent cancer in this patient population. Still, the findings may be worth mentioning to patients considering GLP-1 RAs.

While using GLP-1 RAs specifically to lower cancer risk is “not ready for prime time yet,” the data may offer some reassurance for patients concerned about OACs who already have reason to be prescribed GLP-1 RAs, Michael D. Iglesia, MD, PhD, told Medscape Medical News.

Iglesia, who was not involved in the study, took a more cautious stance on the subgroup findings, first pointing out that women report higher rates of gastrointestinal side effects with GLP-1 RAs, so “the men in this study may have received more consistent GLP-1 RA exposure.”

Commenting on the negative findings among Black patients in the study, Iglesia, who is a medical oncologist at the UNC Lineberger Comprehensive Cancer Center pointed out that this subgroup comprised only 82 GLP-1 RA users and 106 people on diet or exercise.

“Issues related to structural inequality and access to care often affect this kind of study,” he said, adding that further work on social and structural factors is needed “before we posit any biological underpinnings for this observed difference.”

What Questions Remain?

Hsu and colleagues called for long-term prospective trials and postmarketing surveillance to track cancer outcomes among GLP-1 RA users, particularly younger patients.

Underlying mechanisms remain a key unknown, the investigators noted, as it remains unclear whether GLP-1 RAs lower cancer risk through weight loss, direct effects on cancer cells, or some combination thereof.

“Knowing the mechanism behind the association shown in this paper would be important for understanding which cancer types may be treated best with GLP-1 RAs,” Iglesia said.

The investigators and Iglesia reported having no conflicts of interest.

A version of this article first appeared on Medscape.com.

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

An investigational oral drug that targets RAS, the dominant oncogenic driver in pancreatic cancer, nearly doubled overall survival compared with common second-line chemotherapy regimens in patients with previously treated metastatic disease.

In the 500-patient phase 3 RASolute 302 trial, patients who received daraxonrasib, a RAS(ON) multi-selective inhibitor, lived a median of 13.2 months compared with 6.7 months for those who received chemotherapy. The drug also doubled progression-free survival, tripled the response rate, and delayed deterioration in both pain and quality of life.

“Results from RASolute 302 support daraxonrasib as a new standard of care for patients with previously treated metastatic pancreatic cancer,” said lead investigator Brian Wolpin, MD, MPH, director of the Hale Family Center for Pancreatic Cancer Research, Dana-Farber Cancer Institute in Boston, who presented the findings at the American Society of Clinical Oncology (ASCO) 2026. The study was also published simultaneously on May 31 in The New England Journal of Medicine.

Pancreatic ductal adenocarcinoma is one of the most lethal cancers, with most patients presenting with advanced disease at diagnosis. For those whose cancer progresses after first-line chemotherapy, no single standard second-line treatment has been established. Available regimens typically produce median progression-free survival of 3-4 months and a median overall survival of 6-7 months.

More than 90% of pancreatic cancers harbor activating RAS mutations — most commonly KRAS G12D and G12V — that drive tumor growth. The first approved KRAS inhibitors — sotorasib and adagrasib for certain lung and colorectal cancers — target KRAS G12C, which is rare in pancreatic cancer. So far, no RAS-targeted therapy has been approved for pancreatic cancer.

Daraxonrasib takes a broader approach. The oral agent can target a range of RAS variants, including mutant and wild-type RAS, by binding the active form of RAS and blocking downstream signaling.

In the phase 3 open-label RASolute 302 trial, researchers randomized 500 patients with previously treated metastatic pancreatic cancer 1:1 to receive daraxonrasib 300 mg orally once daily or investigator’s choice of chemotherapy. The most used regimens in the control arm were gemcitabine plus nab-paclitaxel (56.5%) and liposomal irinotecan plus fluorouracil and leucovorin (32.7%).

Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1. Documented RAS mutational status was required, and nearly 92% of patients had RAS G12 mutations.

The dual primary endpoints were overall survival and progression-free survival in the RAS G12 population. Key secondary endpoints included the same measures in the overall population as well as objective response rate and patient-reported quality of life. The median follow-up was 8.5 months.

In the RAS G12 population, daraxonrasib reduced the risk for death by 60% (hazard ratio [HR], 0.40; P < .001). The median overall survival was 13.2 months with daraxonrasib vs 6.6 months with chemotherapy. Results were nearly identical in the overall population: 13.2 vs 6.7 months (HR, 0.40; P < .001).

Progression-free survival in the RAS G12 population was 7.3 vs 3.5 months (HR, 0.45; P < .001). The objective response rate was 33.2% vs 11.8%.

Daraxonrasib significantly delayed deterioration in pain (median, 9.0 vs 3.7 months; HR, 0.51; P < .001) and global quality of life (5.6 vs 2.4 months; HR, 0.60; P < .001).

Treatment-related adverse events of grade ≥ 3 occurred in 43.6% of patients on daraxonrasib vs 57.5% of patients on chemotherapy. The most common high-grade events with daraxonrasib were rash (13.7%) and stomatitis (12.0%), whereas neutropenia (27.6%) and anemia (16.4%) were most common with chemotherapy.

One patient in the daraxonrasib arm died from treatment-related pneumonitis. Discontinuation due to adverse events occurred in 1.2% of patients on daraxonrasib vs 11.2% of patients on chemotherapy.

The median duration of treatment was 6.2 months with daraxonrasib vs 1.5-3.2 months across chemotherapy regimens, and 42% of patients on daraxonrasib remained on treatment at data cutoff, Wolpin said.

The open-label design is a limitation. About 15% of patients randomized to chemotherapy never received treatment, largely after learning their treatment assignment, although all were included in the intention-to-treat analysis.

Invited discussant Jennifer Knox, MD, a medical oncologist at Princess Margaret Cancer Center and professor of medicine at the University of Toronto in Toronto, Ontario, Canada, called daraxonrasib a game changer, describing the drug as “probably the most exciting strategy in five decades” for pancreatic cancer.

“It is an absolutely beautiful curve,” Knox said of the overall survival data, noting that the Kaplan-Meier curves separated early and continued to widen over time — a pattern rarely seen in pancreatic cancer trials where initial separation between treatment arms typically narrows as patients in both groups deteriorate.

Knox highlighted the pain and quality-of-life data as “the most important endpoints for our patients,” given the severity of the disease.

She pointed out, however, that the combination of rash and stomatitis will be “challenging” in practice, and called for improved supportive care and closer collaboration with dermatology as oncologists gain experience with this first-in-class drug.

Knox said RAS-targeted therapy “should dominate trials across the full spectrum of pancreatic cancer clinical presentations,” pointing to first-line combination trials already underway and noting that treating a larger, earlier population would have the greatest impact.

“This is the first glimpse at the real power of targeting RAS in pancreas cancer,” Knox said.

The study was funded by Revolution Medicines. Wolpin reported consulting or advisory roles with Revolution Medicines, Mirati Therapeutics, Ipsen, and others, and institutional research funding from Revolution Medicines, Agios, Amgen, AstraZeneca, Lilly, and Novartis. Knox reported receiving honoraria from Astellas Pharma, AstraZeneca, Incyte, and Ipsen, and consulting or advisory roles with AstraZeneca/MedImmune, Incyte, and Ipsen.

A version of this article was previously published on Medscape.com.

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds. 

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds. 

A US Department of Veterans Affairs (VA) Office of Inspector General (OIG) report has found that many patients who scored high on a screening for alcohol use are not receiving recommended counseling interventions.

The OIG report evaluated Veterans Health Administration (VHA) primary care staff adherence to the screening requirements and intervention interventions during fiscal year 2024 (October 1, 2023, to September 30, 2024). VHA primary care clinicians used the Alcohol Use Disorders Identification Test – Consumption (AUDIT-C), which produces a score of 0 to 12, to screen almost 4 million patients.

Based on sex-specific thresholds, the report found 8% of men and 11% of women screened positive for unhealthy alcohol use (AUDIT-C score ≥ 4 for men and ≥ 3 for women). However, because VHA electronic health record prompts clinicians to provide intervention for patients with scores ≥ 5, 54% of men and 75% of women who may have benefited from brief intervention did not.

A brief intervention with a clinician consists of a 5-minute counseling session, with individualized feedback and a discussion on strategies for the patient to reduce or abstain from alcohol.

Aligning with VHA guidance, clinicians provided brief intervention to 77% of men and 75% of women who recorded an AUDIT-C score ≥ 5. However, < 2% of patients with a score at the sex-specific threshold received brief intervention.  

Veterans have high rates of unhealthy alcohol use, which is associated with increased risk of interpersonal violence and poor health outcomes. In a May 2026 study, 44% of 3117 veterans met criteria for alcohol use disorder; 44% reported past 30-day alcohol use.

The VHA requires annual screening using the AUDIT-C. In a study of 63,397 VHA patients, 25% of women and 28% of men screened positive for unhealthy alcohol use. The prevalence of alcohol and other substance abuse disorders increased with increasing AUDIT-C scores, ranging as high as 82% for women and 69% for men. 

A 2018 analysis found that tailoring the AUDIT-C binge-drinking item, AUDIT-C scoring, or both increased detection of unhealthy alcohol use in women. In 2020, VHA adjusted the binge drinking item for women, reducing it to 4 drinks on an occasion from 6 to characterize binge drinking. Despite this adjustment, the VHA maintained an AUDIT-C score ≥ 5 to prompt brief intervention for both women and men.

A 2022 study of 4148 veterans found that 15% were not properly screened for alcohol despite 1 in 11 met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for alcohol abuse/dependence. A lack of screening may not be the issue, however. In the OIG report, VHA found 95% adherence to alcohol use screening in 2024 using a sample-based performance measure and 79% adherence after transitioning that year to a population-based measure. OIG determined that the population-based measure provides a more accurate representation of screening documentation.

Following the OIG recommendations, VA Under Secretary for Health John J. Bartrum, JD, MBA, provided an action plan to evaluate factors that affect screening, identify facilities for performance improvement, and evaluate the use of sex-specific alcohol use screening thresholds. 

The Association of Veterans Affairs Hematology/Oncology (AVAHO) will provide more than education during a special virtual session on July 18 devoted to 4 rare and ultra-rare disorders in classical hematology. The program includes 2.25 free continuing education credits and the organization hopes it will spur hematology pathways within the US Department of Veterans Affairs (VA) National Oncology Program, according to AVAHO President Nicholas Burwick, MD.

“Guidance on hematology disorders lag far behind oncologic disorders at the national level,” said Burwick, who specializes in hematology and bone marrow transplant at the Veterans Affairs Puget Sound Health Care System in Seattle. 

“Providers are facing real diagnostic and treatment decisions, and there are more and more treatment options available, some with significant cost implications,” Burwick said.

Burwick He is optimistic the session will have a lasting impact. He expanded on the 4 disorders slated for discussion at the meeting: aplastic anemia, thrombotic thrombocytopenic purpura (TTP), hereditary hemorrhagic telangiectasia (HHT), and acquired hemophilia A in a discussion with Federal Practitioner. The interview transcript has been edited for length and clarity.

What is aplastic anemia?

Aplastic anemia is a true bone marrow failure. The marrow stops producing cells. At a referral center like Seattle, we might see a few [cases] a year because we also do bone marrow transplant. Most facilities are probably seeing 1 or 2 a year at most.

Different mechanisms are behind it: immune-mediated causes, genetic predispositions, and acquired toxic injury. In the military population, aplastic anemia due to toxic exposure is a significant concern.

Who tends to develop aplastic anemia?

The age spectrum is broader than people think. We do see it in patients in their 40s and 50s, not just seniors. The general rule has been, if a patient is under 40, pursue transplant; over 40, pursue immunosuppressive therapy. However, that cutoff is somewhat arbitrary. 

What are some things clinicians should understand about this disease? 

Clinicians need to know the diagnostic criteria, what tests to run, how to put in transplant referral requests, and how to get a case on the radar at a transplant center like Nashville or Seattle. 

Patients need referral quickly. They often don’t respond to standard treatments like growth factors, so they end up requiring a lot of transfusions. You don’t want to sit around. 

Even if the transplant happens outside the VA, it usually runs through a transplant center for review first. There’s also the question of whether a condition qualifies as a service-connected disability or if the diagnosis is a presumptive condition for certain exposures.

How often do you see TTP, which produces small blood clots in blood vessels?

Some clinicians may see 1 case every 3 to 4 years, or possibly 1 case in an entire career. There is an inherited form and an acquired form. We’re primarily focused on the acquired autoimmune form, which can present in young adulthood or later.

What should clinicians know?

These patients come in needing urgent treatment. Recognizing the diagnosis quickly, ordering the right tests, and acting fast are all critical. This can be life-threatening within days without treatment.

Treatment involves plasma exchange, which not every facility is equipped to perform. There are also medications: steroids are standard, but there’s also caplacizumab, which is highly specific to TTP and unlikely to be stocked in a VA pharmacy because of how rarely it’s needed. Pharmacies often have to procure it on demand once the diagnosis is made, which can delay care. A key part of managing these cases is knowing who to reach out to and when to transfer a patient to an academic or community partner that has plasma exchange capability.

Are VA clinicians likely to see HHT, an inherited disorder that causes bleeding due to malformed blood vessels?

There’s a misconception that veterans don’t have inherited bleeding disorders, the assumption being that they wouldn’t have gotten into the military (had they had them). But many of these conditions don’t get diagnosed until later in life: symptoms can be mild initially or not present until young adulthood or later. 

Patients might come in with recurrent nosebleeds or unexplained [gastrointestinal] bleeding. We probably all have patients with HHT in our practices without knowing it because we’re not always doing appropriate diagnostic testing.

How are treatments evolving? 

Recent developments include both local options like laser treatment and systemic medications such as pomalidomide, which was approved recently, and bevacizumab. [The virtual session] speaker has been involved in clinical trials for pomalidomide and will speak to when to use these medications and how to choose between them now that there are options, both of which are expensive.

What is acquired hemophilia A?

It occurs when someone without a genetic predisposition loses their factor VIII activity due to an autoimmune process. It presents quickly, often with bleeding or bruising, and patients frequently show up in the [emergency department]. 

The treatment challenge is distinct from inherited hemophilia. Standard factor VIII replacement doesn’t work here because the autoantibody breaks it down. Treatment requires bypassing factor VIII—options include factor VIIa and emicizumab. 

Emicizumab is FDA-approved for inherited hemophilia A and used off-label for the acquired form. Procuring it in a VA facility can be difficult, and that is exactly where a VA clinical pathway would help. 

The VA doesn’t currently have strong hemophilia expertise internally. So, engaging with hemophilia treatment centers is important, as is developing subject matter experts within VA hematology who can serve as go-to resources for less-resourced facilities.

What unites these 4 rare hematology conditions? 

There are common threads: rare presentations requiring urgent decision-making, diagnostic criteria that aren’t always familiar, and treatments that may be hard to procure quickly. VA-specific resources—pathways, referral contacts, teleoncology consults—can make the difference in patient outcomes. 

A centralized virtual hematology hub, where providers could reach a knowledgeable hematologist for consultation, would go a long way. That’s what we’re ultimately trying to build toward.

The AVAHO Virtual Session on Rare and Ultra-Rare Hematologic Disorders will be held on July 18, 2026, from 12-2:30 p.m. EST.

The program is available to any health care professional who wants to learn more about the diagnosis and management of these hematologic disorders; 2.25 free continuing education credits are available.

The speakers are:

• Aplastic anemia: Emma Groarke, MB, BCh, BAO, MD, National Institutes of Health

• Thrombotic thrombocytopenic purpura: Yazan Abou-Ismail, MD, University of Utah

• Hereditary hemorrhagic telangiectasia: Hanny Al-Samkari, MD, Massachusetts General Hospital/Harvard Medical School; and

• Acquired hemophilia A, Aaron Boothby, MD, University of Washington/Fred Hutchinson Cancer Center.

The Association of Veterans Affairs Hematology/Oncology (AVAHO) will provide more than education during a special virtual session on July 18 devoted to 4 rare and ultra-rare disorders in classical hematology. The program includes 2.25 free continuing education credits and the organization hopes it will spur hematology pathways within the US Department of Veterans Affairs (VA) National Oncology Program, according to AVAHO President Nicholas Burwick, MD.

“Guidance on hematology disorders lag far behind oncologic disorders at the national level,” said Burwick, who specializes in hematology and bone marrow transplant at the Veterans Affairs Puget Sound Health Care System in Seattle. 

“Providers are facing real diagnostic and treatment decisions, and there are more and more treatment options available, some with significant cost implications,” Burwick said.

Burwick He is optimistic the session will have a lasting impact. He expanded on the 4 disorders slated for discussion at the meeting: aplastic anemia, thrombotic thrombocytopenic purpura (TTP), hereditary hemorrhagic telangiectasia (HHT), and acquired hemophilia A in a discussion with Federal Practitioner. The interview transcript has been edited for length and clarity.

What is aplastic anemia?

Aplastic anemia is a true bone marrow failure. The marrow stops producing cells. At a referral center like Seattle, we might see a few [cases] a year because we also do bone marrow transplant. Most facilities are probably seeing 1 or 2 a year at most.

Different mechanisms are behind it: immune-mediated causes, genetic predispositions, and acquired toxic injury. In the military population, aplastic anemia due to toxic exposure is a significant concern.

Who tends to develop aplastic anemia?

The age spectrum is broader than people think. We do see it in patients in their 40s and 50s, not just seniors. The general rule has been, if a patient is under 40, pursue transplant; over 40, pursue immunosuppressive therapy. However, that cutoff is somewhat arbitrary. 

What are some things clinicians should understand about this disease? 

Clinicians need to know the diagnostic criteria, what tests to run, how to put in transplant referral requests, and how to get a case on the radar at a transplant center like Nashville or Seattle. 

Patients need referral quickly. They often don’t respond to standard treatments like growth factors, so they end up requiring a lot of transfusions. You don’t want to sit around. 

Even if the transplant happens outside the VA, it usually runs through a transplant center for review first. There’s also the question of whether a condition qualifies as a service-connected disability or if the diagnosis is a presumptive condition for certain exposures.

How often do you see TTP, which produces small blood clots in blood vessels?

Some clinicians may see 1 case every 3 to 4 years, or possibly 1 case in an entire career. There is an inherited form and an acquired form. We’re primarily focused on the acquired autoimmune form, which can present in young adulthood or later.

What should clinicians know?

These patients come in needing urgent treatment. Recognizing the diagnosis quickly, ordering the right tests, and acting fast are all critical. This can be life-threatening within days without treatment.

Treatment involves plasma exchange, which not every facility is equipped to perform. There are also medications: steroids are standard, but there’s also caplacizumab, which is highly specific to TTP and unlikely to be stocked in a VA pharmacy because of how rarely it’s needed. Pharmacies often have to procure it on demand once the diagnosis is made, which can delay care. A key part of managing these cases is knowing who to reach out to and when to transfer a patient to an academic or community partner that has plasma exchange capability.

Are VA clinicians likely to see HHT, an inherited disorder that causes bleeding due to malformed blood vessels?

There’s a misconception that veterans don’t have inherited bleeding disorders, the assumption being that they wouldn’t have gotten into the military (had they had them). But many of these conditions don’t get diagnosed until later in life: symptoms can be mild initially or not present until young adulthood or later. 

Patients might come in with recurrent nosebleeds or unexplained [gastrointestinal] bleeding. We probably all have patients with HHT in our practices without knowing it because we’re not always doing appropriate diagnostic testing.

How are treatments evolving? 

Recent developments include both local options like laser treatment and systemic medications such as pomalidomide, which was approved recently, and bevacizumab. [The virtual session] speaker has been involved in clinical trials for pomalidomide and will speak to when to use these medications and how to choose between them now that there are options, both of which are expensive.

What is acquired hemophilia A?

It occurs when someone without a genetic predisposition loses their factor VIII activity due to an autoimmune process. It presents quickly, often with bleeding or bruising, and patients frequently show up in the [emergency department]. 

The treatment challenge is distinct from inherited hemophilia. Standard factor VIII replacement doesn’t work here because the autoantibody breaks it down. Treatment requires bypassing factor VIII—options include factor VIIa and emicizumab. 

Emicizumab is FDA-approved for inherited hemophilia A and used off-label for the acquired form. Procuring it in a VA facility can be difficult, and that is exactly where a VA clinical pathway would help. 

The VA doesn’t currently have strong hemophilia expertise internally. So, engaging with hemophilia treatment centers is important, as is developing subject matter experts within VA hematology who can serve as go-to resources for less-resourced facilities.

What unites these 4 rare hematology conditions? 

There are common threads: rare presentations requiring urgent decision-making, diagnostic criteria that aren’t always familiar, and treatments that may be hard to procure quickly. VA-specific resources—pathways, referral contacts, teleoncology consults—can make the difference in patient outcomes. 

A centralized virtual hematology hub, where providers could reach a knowledgeable hematologist for consultation, would go a long way. That’s what we’re ultimately trying to build toward.

The AVAHO Virtual Session on Rare and Ultra-Rare Hematologic Disorders will be held on July 18, 2026, from 12-2:30 p.m. EST.

The program is available to any health care professional who wants to learn more about the diagnosis and management of these hematologic disorders; 2.25 free continuing education credits are available.

The speakers are:

• Aplastic anemia: Emma Groarke, MB, BCh, BAO, MD, National Institutes of Health

• Thrombotic thrombocytopenic purpura: Yazan Abou-Ismail, MD, University of Utah

• Hereditary hemorrhagic telangiectasia: Hanny Al-Samkari, MD, Massachusetts General Hospital/Harvard Medical School; and

• Acquired hemophilia A, Aaron Boothby, MD, University of Washington/Fred Hutchinson Cancer Center.

The Association of Veterans Affairs Hematology/Oncology (AVAHO) will provide more than education during a special virtual session on July 18 devoted to 4 rare and ultra-rare disorders in classical hematology. The program includes 2.25 free continuing education credits and the organization hopes it will spur hematology pathways within the US Department of Veterans Affairs (VA) National Oncology Program, according to AVAHO President Nicholas Burwick, MD.

“Guidance on hematology disorders lag far behind oncologic disorders at the national level,” said Burwick, who specializes in hematology and bone marrow transplant at the Veterans Affairs Puget Sound Health Care System in Seattle. 

“Providers are facing real diagnostic and treatment decisions, and there are more and more treatment options available, some with significant cost implications,” Burwick said.

Burwick He is optimistic the session will have a lasting impact. He expanded on the 4 disorders slated for discussion at the meeting: aplastic anemia, thrombotic thrombocytopenic purpura (TTP), hereditary hemorrhagic telangiectasia (HHT), and acquired hemophilia A in a discussion with Federal Practitioner. The interview transcript has been edited for length and clarity.

What is aplastic anemia?

Aplastic anemia is a true bone marrow failure. The marrow stops producing cells. At a referral center like Seattle, we might see a few [cases] a year because we also do bone marrow transplant. Most facilities are probably seeing 1 or 2 a year at most.

Different mechanisms are behind it: immune-mediated causes, genetic predispositions, and acquired toxic injury. In the military population, aplastic anemia due to toxic exposure is a significant concern.

Who tends to develop aplastic anemia?

The age spectrum is broader than people think. We do see it in patients in their 40s and 50s, not just seniors. The general rule has been, if a patient is under 40, pursue transplant; over 40, pursue immunosuppressive therapy. However, that cutoff is somewhat arbitrary. 

What are some things clinicians should understand about this disease? 

Clinicians need to know the diagnostic criteria, what tests to run, how to put in transplant referral requests, and how to get a case on the radar at a transplant center like Nashville or Seattle. 

Patients need referral quickly. They often don’t respond to standard treatments like growth factors, so they end up requiring a lot of transfusions. You don’t want to sit around. 

Even if the transplant happens outside the VA, it usually runs through a transplant center for review first. There’s also the question of whether a condition qualifies as a service-connected disability or if the diagnosis is a presumptive condition for certain exposures.

How often do you see TTP, which produces small blood clots in blood vessels?

Some clinicians may see 1 case every 3 to 4 years, or possibly 1 case in an entire career. There is an inherited form and an acquired form. We’re primarily focused on the acquired autoimmune form, which can present in young adulthood or later.

What should clinicians know?

These patients come in needing urgent treatment. Recognizing the diagnosis quickly, ordering the right tests, and acting fast are all critical. This can be life-threatening within days without treatment.

Treatment involves plasma exchange, which not every facility is equipped to perform. There are also medications: steroids are standard, but there’s also caplacizumab, which is highly specific to TTP and unlikely to be stocked in a VA pharmacy because of how rarely it’s needed. Pharmacies often have to procure it on demand once the diagnosis is made, which can delay care. A key part of managing these cases is knowing who to reach out to and when to transfer a patient to an academic or community partner that has plasma exchange capability.

Are VA clinicians likely to see HHT, an inherited disorder that causes bleeding due to malformed blood vessels?

There’s a misconception that veterans don’t have inherited bleeding disorders, the assumption being that they wouldn’t have gotten into the military (had they had them). But many of these conditions don’t get diagnosed until later in life: symptoms can be mild initially or not present until young adulthood or later. 

Patients might come in with recurrent nosebleeds or unexplained [gastrointestinal] bleeding. We probably all have patients with HHT in our practices without knowing it because we’re not always doing appropriate diagnostic testing.

How are treatments evolving? 

Recent developments include both local options like laser treatment and systemic medications such as pomalidomide, which was approved recently, and bevacizumab. [The virtual session] speaker has been involved in clinical trials for pomalidomide and will speak to when to use these medications and how to choose between them now that there are options, both of which are expensive.

What is acquired hemophilia A?

It occurs when someone without a genetic predisposition loses their factor VIII activity due to an autoimmune process. It presents quickly, often with bleeding or bruising, and patients frequently show up in the [emergency department]. 

The treatment challenge is distinct from inherited hemophilia. Standard factor VIII replacement doesn’t work here because the autoantibody breaks it down. Treatment requires bypassing factor VIII—options include factor VIIa and emicizumab. 

Emicizumab is FDA-approved for inherited hemophilia A and used off-label for the acquired form. Procuring it in a VA facility can be difficult, and that is exactly where a VA clinical pathway would help. 

The VA doesn’t currently have strong hemophilia expertise internally. So, engaging with hemophilia treatment centers is important, as is developing subject matter experts within VA hematology who can serve as go-to resources for less-resourced facilities.

What unites these 4 rare hematology conditions? 

There are common threads: rare presentations requiring urgent decision-making, diagnostic criteria that aren’t always familiar, and treatments that may be hard to procure quickly. VA-specific resources—pathways, referral contacts, teleoncology consults—can make the difference in patient outcomes. 

A centralized virtual hematology hub, where providers could reach a knowledgeable hematologist for consultation, would go a long way. That’s what we’re ultimately trying to build toward.

The AVAHO Virtual Session on Rare and Ultra-Rare Hematologic Disorders will be held on July 18, 2026, from 12-2:30 p.m. EST.

The program is available to any health care professional who wants to learn more about the diagnosis and management of these hematologic disorders; 2.25 free continuing education credits are available.

The speakers are:

• Aplastic anemia: Emma Groarke, MB, BCh, BAO, MD, National Institutes of Health

• Thrombotic thrombocytopenic purpura: Yazan Abou-Ismail, MD, University of Utah

• Hereditary hemorrhagic telangiectasia: Hanny Al-Samkari, MD, Massachusetts General Hospital/Harvard Medical School; and

• Acquired hemophilia A, Aaron Boothby, MD, University of Washington/Fred Hutchinson Cancer Center.

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE: Serum P21 Activated Kinase 6 (PAK6) demonstrated diagnostic accuracy comparable to pro-gastrin-releasing peptide (ProGRP) for small cell lung cancer (SCLC), with area under the curve (AUC) values of 0.892 and 0.935, respectively, in a study of 109 patients with SCLC. Combining PAK6, ProGRP, and neuron-specific enolase (NSE) achieved diagnostic efficiency of 0.98. Elevated baseline PAK6 levels correlated with shorter progression-free survival and increased risk for disease progression.

METHODOLOGY:

• Participants included 380 people in China: 109 with SCLC, 92 with non–small cell lung cancer (NSCLC), 85 with benign pulmonary nodules, and 94 healthy controls who received routine physical examinations. 

• Laboratory testing measured serum PAK6 by ELISA, while NSE, carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and ProGRP were quantified by chemiluminescence. 

• Pretreatment and posttreatment serum samples from 56 patients with SCLC were analyzed to evaluate changes in biomarker levels following 3 months of treatment. 

• Progression-free survival data were collected through case review and follow-up, defined as time from treatment initiation to radiographic disease progression per RECIST 1.1 criteria or death from any cause.

TAKEAWAY:

• Median serum PAK6 is reported as 56.44 ng/L in SCLC vs 41.06 ng/L in NSCLC, 37.82 ng/L in pulmonary nodules, and 34.75 ng/L in healthy controls (P < .01). 

• PAK6 demonstrated diagnostic efficacy with and AUC of 0.892 (95% CI, 0.857-0.927), sensitivity of 0.82, and specificity of 0.86 at optimal cut-off value of 47.30 ng/L, comparable to ProGRP (AUC, 0.935) and superior to CEA (AUC, 0.676) and CA19-9 (AUC, 0.611). 

• In 56 paired SCLC samples, PAK6, NSE, and ProGRP decrease after 3 months of treatment (P < .001), while CEA and CA19-9 display no meaningful change. 

• Elevated baseline PAK6 expression correlated with shorter progression-free survival, with high-expression patients demonstrating median survival of 92 days vs 194 days in low-expression patients (HR, 2.02; 95% CI, 1.33-3.07; P = .001).

IN PRACTICE: “We identify PAK6 as a multi-faceted biomarker for SCLC with diagnostic, prognostic, and therapeutic monitoring value. Its cost-effective ELISA quantification facilitates clinical translation,” wrote the authors of the study. “Integrating PAK6 with emerging technologies could further refine SCLC management paradigms.”

SOURCE:The study was led by Simei Chen, Department of Blood Transfusion, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University in Nanchang, China. It was published online in PeerJ.

LIMITATIONS: A single-center design and modest sample size may limit generalizability of the diagnostic and prognostic estimates. The authors also note the absence of immunohistochemical validation, leaving tissue-level correlation of PAK6 unaddressed. Finally, insufficient overall survival data were reported, which constrains interpretation beyond PFS and supports the need for prospective follow-up and larger multi-center validation.

DISCLOSURES: Grant support came from the Science and Technology Program Project of Jiangxi Provincial Administration of Traditional Chinese Medicine (Grant 2024B1433). The authors stated the funders had no role in study design, data collection and analysis, the decision to publish, or manuscript preparation. No competing interests were disclosed.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.