Lung Cancer

TOPLINE:

Compared with inactive patterns, weekend warrior (moderate-to-vigorous physical activity [MVPA] condensed into 1-2 days per week) and regular physical activity patterns were found to be equally effective at reducing the risk for lung cancer. Neither pattern showed significant associations with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

METHODOLOGY:

• This analysis included 80,896 participants (mean age, 55.5 years; 56% women) with valid accelerometer data collected between June 2013 and December 2015.
• Participants were classified into three groups: 32,213 active weekend warriors (≥ 150 minutes of weekly MVPA with ≥ 50% achieved in 1-2 days), 22,162 active regular participants (≥ 150 minutes of MVPA but not meeting a weekend warrior pattern), and 26,521 inactive participants (< 150 minutes of MVPA).
• Researchers tracked associations between physical activity patterns and incident cases of all types of cancer plus specific cases of prostate, breast, colorectal, and lung cancer over a median follow-up duration of 6 years.

TAKEAWAY:

• Compared with inactive patterns, active weekend warrior patterns showed a significant inverse association with the risk for lung cancer (hazard ratio [HR], 0.77; 95% CI, 0.61-0.98).
• Active regular activity patterns demonstrated similar protective effects against lung cancer as inactive patterns (HR, 0.73; 95% CI, 0.56-0.96).
• Neither of the physical activity patterns showed any significant association with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

IN PRACTICE:

"Physical activity condensed into one to two days per week compared with a more balanced weekly distribution was associated with similar risk reductions of incident lung cancer, while neither pattern was associated with reduced overall, prostate, breast, and colorectal cancers," the authors of the study wrote.

SOURCE:

This study was led by Rubén López-Bueno, Department of Physical Medicine and Nursing, University of Zaragoza, Zaragoza, Spain. It was published online on September 06, 2025, in Annals of Medicine.

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

TOPLINE:

Compared with inactive patterns, weekend warrior (moderate-to-vigorous physical activity [MVPA] condensed into 1-2 days per week) and regular physical activity patterns were found to be equally effective at reducing the risk for lung cancer. Neither pattern showed significant associations with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

METHODOLOGY:

• This analysis included 80,896 participants (mean age, 55.5 years; 56% women) with valid accelerometer data collected between June 2013 and December 2015.
• Participants were classified into three groups: 32,213 active weekend warriors (≥ 150 minutes of weekly MVPA with ≥ 50% achieved in 1-2 days), 22,162 active regular participants (≥ 150 minutes of MVPA but not meeting a weekend warrior pattern), and 26,521 inactive participants (< 150 minutes of MVPA).
• Researchers tracked associations between physical activity patterns and incident cases of all types of cancer plus specific cases of prostate, breast, colorectal, and lung cancer over a median follow-up duration of 6 years.

TAKEAWAY:

• Compared with inactive patterns, active weekend warrior patterns showed a significant inverse association with the risk for lung cancer (hazard ratio [HR], 0.77; 95% CI, 0.61-0.98).
• Active regular activity patterns demonstrated similar protective effects against lung cancer as inactive patterns (HR, 0.73; 95% CI, 0.56-0.96).
• Neither of the physical activity patterns showed any significant association with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

IN PRACTICE:

"Physical activity condensed into one to two days per week compared with a more balanced weekly distribution was associated with similar risk reductions of incident lung cancer, while neither pattern was associated with reduced overall, prostate, breast, and colorectal cancers," the authors of the study wrote.

SOURCE:

This study was led by Rubén López-Bueno, Department of Physical Medicine and Nursing, University of Zaragoza, Zaragoza, Spain. It was published online on September 06, 2025, in Annals of Medicine.

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

TOPLINE:

Compared with inactive patterns, weekend warrior (moderate-to-vigorous physical activity [MVPA] condensed into 1-2 days per week) and regular physical activity patterns were found to be equally effective at reducing the risk for lung cancer. Neither pattern showed significant associations with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

METHODOLOGY:

• This analysis included 80,896 participants (mean age, 55.5 years; 56% women) with valid accelerometer data collected between June 2013 and December 2015.
• Participants were classified into three groups: 32,213 active weekend warriors (≥ 150 minutes of weekly MVPA with ≥ 50% achieved in 1-2 days), 22,162 active regular participants (≥ 150 minutes of MVPA but not meeting a weekend warrior pattern), and 26,521 inactive participants (< 150 minutes of MVPA).
• Researchers tracked associations between physical activity patterns and incident cases of all types of cancer plus specific cases of prostate, breast, colorectal, and lung cancer over a median follow-up duration of 6 years.

TAKEAWAY:

• Compared with inactive patterns, active weekend warrior patterns showed a significant inverse association with the risk for lung cancer (hazard ratio [HR], 0.77; 95% CI, 0.61-0.98).
• Active regular activity patterns demonstrated similar protective effects against lung cancer as inactive patterns (HR, 0.73; 95% CI, 0.56-0.96).
• Neither of the physical activity patterns showed any significant association with the overall risk for cancer or specific risks for prostate, breast, and colorectal cancers.

IN PRACTICE:

"Physical activity condensed into one to two days per week compared with a more balanced weekly distribution was associated with similar risk reductions of incident lung cancer, while neither pattern was associated with reduced overall, prostate, breast, and colorectal cancers," the authors of the study wrote.

SOURCE:

This study was led by Rubén López-Bueno, Department of Physical Medicine and Nursing, University of Zaragoza, Zaragoza, Spain. It was published online on September 06, 2025, in Annals of Medicine.

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

Background

Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.

Objective

To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).

Methods

The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.

Results

In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.

Conclusions

This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.

Background

Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.

Objective

To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).

Methods

The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.

Results

In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.

Conclusions

This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.

Background

Patients diagnosed with lung cancer are predominantly non-small cell lung cancer (NSCLC), a leading cause of cancer-related deaths. Thus, it is imperative to investigate and distinguish the differences present at diagnosis to possibly improve survival outcomes. NSCLC commonly metastasizes within older patients near the mean age of 71 years, but also in early onset patients which represents the patients younger than the earliest lung cancer screening age of 50.

Objective

To reveal differences in ratios of metastasis locations in squamous cell carcinoma (SCC), adenocarcinoma (ACC), and adenosquamous carcinoma (ASC).

Methods

The National Cancer Database (NCDB) was utilized to identify patients diagnosed with SCC, ACC, and ASC using the histology codes 8070, 8140, and 8560 from the ICD-O-3.2 from 2004 to 2022. Age groups were 70 years. Metastases located to the brain, liver, bone, and lung were included. Chi-Square tests were performed. The data was analyzed using R version 4.4.2 and statistical significance was set to α = 0.05.

Results

In this study, 1,445,119 patients were analyzed. Chi-Square tests identified significant differences in the ratios of organ metastasis locations between age groups in each subtype (p < 0.001). SCC in each age group similarly metastasized most to bone (36.3%, 34.7%, 34.5%), but notably more local lung metastasis was observed in the oldest group (33.6%). In ACC and ASC, the oldest group also had greater ratios of spread within the lungs (28.0%, 27.2%). Overall, the younger the age group, distant spread to the brain increased (ex. 29.0%, 24.4%, 17.5%). This suggests a widely heterogenous distribution of metastases at diagnosis of NSCLC subtypes and patient age.

Conclusions

This study demonstrated that patients with SCC, ACC, or ASC subtypes of NSCLC share similar predominant locations based in part on patient age, irrespective of cancer origin. NSCLC may more distantly metastasize in younger patients to the brain, while older patients may have locally metastatic cancer. Further analysis of key demographic variables as well as common undertaken treatment options may prove informative and reveal existing differences in survival outcomes.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune checkpoint inhibitors, including pembrolizumab, are associated with a spectrum of immune-related adverse events (irAEs), including immune- mediated hepatitis. Typically, this toxicity manifests within the first 14 weeks of therapy. Delayed presentations beyond one year are exceedingly rare and pose diagnostic challenges.

Case Presentation

We report an elderly patient (over 90 years old) with stage IVa squamous cell carcinoma of the lung and high microsatellite instability (MSI) who had been receiving pembrolizumab since 2023. In 2024—13 months into therapy—he presented with subjective fevers, weakness, and altered mental status. Laboratory evaluation revealed cholestatic jaundice with AST 310 U/L, ALT 291 U/L, alkaline phosphatase 860 U/L, and total bilirubin 5.7 mg/dL. Infectious workup was negative. Imaging via MRCP showed multiple scattered hepatic cysts and a small pancreatic cyst, without biliary obstruction.

Further evaluation, including serologies for hepatitis B and C, CMV, HSV, autoimmune hepatitis panel, iron studies, and ceruloplasmin, was unremarkable except for mildly elevated alpha-1 antitrypsin. Scattered liver cysts were seen on an MRI. The overall findings were most consistent with immune-related hepatitis, as pembrolizumab is known to cause both hepatocellular and cholestatic patterns of liver injury.

The patient was started on high-dose prednisone, resulting in rapid clinical and biochemical improvement. Two weeks post-discharge, liver function tests (LFTs) had markedly improved (bilirubin 1.3, AST 19, ALT 40, ALP 193). Given the severity of transaminitis and hyperbilirubinemia (AST >8x ULN, bilirubin >3x ULN), pembrolizumab was permanently discontinued. LFTs normalized after completion of the steroid taper.

Conclusions

This case highlights a rare instance of delayed immune-related hepatitis occurring over a year after initiation of pembrolizumab, far beyond the typical window of onset. Clinicians should maintain a high index of suspicion for irAEs even in late stages of immunotherapy, particularly when common etiologies are excluded. Prompt recognition and corticosteroid treatment can lead to favorable outcomes, even in older patients.

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?

Background

Immune related adverse events (irAE) are a well-known complication in the treatment of nonsmall cell lung cancer (NSCLCA) with checkpoint inhibitors and have been shown to improve overall survival (OS) and progression free survival (PFS) across multiple studies. However, studies have shown that the prognosis of NSCLCA differs depending on the type of immune related adverse event and the grade of the irAE. For instance, patients who experienced endocrine irAEs like thyroid, or adrenal insufficiency tended to have an improved OS and PFS, whereas patients who developed pneumonitis that required discontinuation of checkpoint inhibitors had worse OS and PFS. While the literature describes the prognostic impacts of irAEs on NSCLCA, there is still a dearth of information on the implications of HLA supertypes on the prognosis of NSCLCA following irAEs.

Case Presentation

To address this point and to ask a question, we would like to share the case of a patient with a 10-year history of inflammatory arthropathy related to HLA-B27 antigen prior to his diagnosis of T2bN2M1b adenosquamous lung cancer with liver metastases. The tumor was 100% PD-L1 expressive and the patient was treated with pembrolizumab. The patient developed central adrenal insufficiency 10 months after pembrolizumab was initiated which was treated with physiologic dosing of hydrocortisone. The patient later developed a grade 3 pneumonitis 62 months after initiation of pembrolizumab and was treated with systemic glucocorticoids. Due to recurrent hospitalizations for pneumonitis, pembrolizumab was discontinued at 70 months post initiation. At the time of discontinuation PET was positive. However, there was a decrease in hyperactivity of the primary tumor at 4 months post discontinuation of pembrolizumab and there have been serial negative PETS from 7 months to 13 months post discontinuation. This led us to ask the question of whether HLA-B27 is protective of the poor prognostic immune related pneumonitis in this patient?

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.

Background

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung cancer subtype, comprising ~3% of lung malignancies. It commonly affects older, heavy smokers and presents at an advanced stage. Prognosis is poor, with a 5-year survival rate of 15–25% in metastatic disease.

Case Presentation

A 33-year-old previously healthy male presented with a month of abdominal and lower back pain, along with significant weight loss. Lab tests revealed elevated lipase (378), and he was initially treated for acute pancreatitis. Imaging revealed a 1.9 cm pancreatic head mass and three hypodense hepatic lesions. MRI confirmed these findings but remained inconclusive. An incidental 8 mm right lower lobe pulmonary nodule led to chest CT, identifying a dominant left lower lobe mass and mediastinal lymphadenopathy, raising suspicion for primary lung malignancy. The patient was discharged but returned three days later with worsening symptoms and a lipase of 754. Endoscopic biopsy of the pancreatic mass was deferred due to ongoing pancreatitis. A liver biopsy revealed neuroendocrine differentiation, positive for CK AE1/AE3, CK7, CK19, and synaptophysin. Molecular profiling showed PD-L1 (TPS 50%), low tumor mutational burden, microsatellite stability, and high loss of heterozygosity. Bronchoscopy revealed a left hilar mass, and lymph node biopsy confirmed LCNEC (CK7+, chromogranin+, TTF- 1+, synaptophysin+), establishing a diagnosis of stage IV pulmonary LCNEC with pancreatic and liver metastases. The patient began treatment with bevacizumab, paclitaxel, carboplatin, and atezolizumab, resulting in improvement in hilar, hepatic, and pancreatic lesions on further imagings. The patient was continued on chemoimmunotherapy.

Discussion

This case highlights an uncommon presentation of LCNEC in a young, non-smoking male, initially manifesting as pancreatitis due to pancreatic metastasis. The absence of pulmonary symptoms complicated the diagnosis. Histopathology and immunohistochemistry were essential. While no standardized treatment exists for LCNEC, platinum-based chemotherapy with immunotherapy remains the mainstay. PD-L1 expression may guide immunotherapy decisions.

Conclusions

Pulmonary LCNEC should be considered in metastatic neuroendocrine tumors, even in young, non-smoking patients without pulmonary symptoms. Early tissue diagnosis and molecular profiling are key to guiding management.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

Lung cancer, primarily non-small cell lung cancer (NSCLC), typically presents at an advanced stage with a five-year survival rate below 5%. Treatment includes platinum-based chemotherapy and targeted therapies for specific mutations, with immunotherapy significantly improving outcomes for patients with high PD-L1 expression.

Case Presentation

A 72-year-old male, diagnosed with advanced lung adenocarcinoma in 2020 after showing symptoms of brain metastases, underwent successful surgical and CyberKnife treatments. Despite no actionable genetic targets and a high PD-L1 expression of 80%, his treatment with 3-cycles of Keytruda was cut short due to a psoriatic arthritis flare-up, though it initially decreased his CEA levels significantly. Over the following years, fluctuating CEA levels and various imaging studies indicated some concerning changes, such as potential radionecrosis or recurrence of cancer in the lung. His refusal of biopsy and a preference for avoiding invasive treatments led to only surveillance. Later, an MRI showed some metastasis, and the patient agreed to a lung biopsy, which showed poorly differentiated carcinoma of pulmonary origin. The patient only agreed to restart treatment with Keytruda 4-years later after his initial treatment with Keytruda, under close rheumatological care, and received only two doses. Afterward, the patient lost follow-ups. 3-months later, Repeated CT scans of the chest, abdomen, and pelvis showed no evidence of mass or pathological lymph nodes, and repeated CEA was 3.4.

Discussion

Managing advanced lung adenocarcinoma, especially with complications like brain metastases and psoriatic arthritis, is challenging. Pembrolizumab treatment showed promise by significantly reducing CEA levels despite early discontinuation due to autoimmune side effects, indicating effective tumor response in patients with high PD-L1 expression. The case underscores the need for balancing cancer treatment with autoimmune management and highlights the importance of patient preferences in treatment plans. Ongoing surveillance and genomic profiling remain crucial for guiding therapy.

Conclusions

This case of a 70-year-old male with advanced lung adenocarcinoma highlights the significant impact of immunotherapy, particularly PD-1/ PD-L1 inhibitors like pembrolizumab, in NSCLC. Despite a brief treatment period, the patient experienced extended disease control, demonstrating the potential of immunotherapy to enhance survival and its broad applicability in oncology.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

Background

The Exposome—the comprehensive accumulation of environmental exposures from birth to death—provides a framework for linking external risk factors to cancer biology. In U.S. veterans, the exposome includes both military-specific exposures (e.g., asbestos, Agent Orange, burn pits) and postservice socioeconomic and environmental factors. These cumulative exposures may drive tumor development and progression via epigenetic mechanisms, though their impact on lung cancer outcomes remain poorly characterized.

Methods

This is a retrospective cohort study of 71 lung cancer subjects (NSCLC and SCLC) from the Jesse Brown VA Medical Center (IRB# 1586320). We assessed the Area Deprivation Index (ADI), Environmental Burden Index (EBI), and occupational exposure in relation to DNA methylation of CDO1, TAC1, SOX17, and HOXA7. Geospatial data were mapped to US census tracts, and standard statistical analysis were conducted.

Results

NSCLC patients exhibited significantly higher methylation levels across all genes. High EBI exposure was associated with lower SOX17 methylation (p = 0.064) and worse overall survival (p = 0.046). In NSCLC patients, occupational exposure predicted a 7.7-fold increased hazard of death (p = 0.027). SOX17 and TAC1 methylation were independently associated with reduced survival (p = 0.037 and 0.0058, respectively). While ADI did not independently predict survival, it correlated with late-stage presentation and reduced HOXA7 methylation.

Conclusions

Exposome factors such as environmental burden and occupational exposure are biologically embedded in lung cancer cell through gene-specific methylation and significantly impact survival. We posit that integrating exposomic and molecular data could enhance lung precision oncology approaches for high-risk veteran populations.

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

This transcript has been edited for clarity. 

Hello. It’s Mark Kris, from Memorial Sloan Kettering, talking about a birthday gift I received on June 23 when the FDA approved the indication of datopotamab deruxtecan for people with lung cancers. We have another drug, our third ADC (antibody-drug conjugate) to fight lung cancer, so that’s a gift. 

Let’s talk a little bit about that agent. It’s an interesting twist in our practice patterns. What can the drug do? It had a response rate of 45%, which is really important in patients that had EGFR mutations with progression on osimertinib. We really need drugs in that space. The duration of response was about 7 months, which is significant.

One interesting thing in the approval, [was] that the response rate of the blinded folks was greater than that in the investigator-assessed response by about 10%. It’s very interesting. Clearly, we have another drug, and we have it in a space where we need it. 

Let’s talk a bit about the toxicity. I’m going to focus more on the paper by Bardia et al that compared datopotamab deruxtecan to various chemo drugs in breast cancer, not in lung cancer. You can take this a little bit with a grain of salt. 

First, they saw a whole different array of side effects with datopotamab deruxtecan, things that we don’t normally deal with here. Nausea, stomatitis, alopecia, dry eye, and vomiting. All of those were more than 10% more common in patients that received datopotamab deruxtecan compared to the control. The only things that were more common with the control were neutropenia, leukopenia, and hand-foot syndrome in patients that had capecitabine. 

One thing, though, is while you say, “Oh, these weren’t dangerous side effects,” they surely were lifestyle altering. Nobody wants to have these side effects on a daily basis. Again, there’s an increasing awareness about these kinds of lower-grade but still lifestyle-disrupting side effects. When it goes on day after day, you really have to balance that into the benefit you’re going to receive.

I think the second important point is how, when we use this drug, we’re going to have to go to another level to deal with the adverse effects that we are going to see. The first would be nausea and emesis. It is a highly emetogenic regimen based on the NCCN (National Comprehensive Cancer Network) guidelines, so you would need either 3 or 4 antiemetic drugs. That’s number one. 

Number two, because of the potential eye problems, you need an eye exam before treatment — and the label says at least annually — with any symptoms. I think it’s very important that you give the patients eyedrops, and in general, the preservative-free eyedrops are the ones that are most effective.

Stomatitis is a very common side effect with that agent. It’s really not seen with the other drugs that even contain the same warhead. There, dexamethasone rinses are important. Now, this is a compounded medicine so you need to be very careful in making sure that you identify pharmacies that will prepare this and will have it available for the patients that need it.

Last, there is the risk of hypersensitivity reactions and there’s a recommendation for premedication for that. As you think about using datopotamab deruxtecan, you need to have all your ducks in a row to treat side effects. You need prophylaxis for hypersensitivity reactions, nausea, and emesis. 

The patient will need an eye exam. You need to prepare the patient for possible dry eye and teach them which eyedrops are the best. You also need to ensure the availability of dexamethasone rinses and mouth washes. All that needs to be in place to make sure that the patient can safely use the drug. 

I think it’s going to be a useful drug. We don’t yet have a uniformly available way to select patients for its use other than EGFR. I should note that the approval is for EGFR-mutated lung cancers. It doesn’t say which type of mutation, so that would give you some latitude in giving it for exon 20 atypicals as well as for the common sensitizing mutation.

We have another drug. It’s clearly going to be a useful one. It clearly comes with many adverse effects that we don’t normally treat on an everyday basis, we’re used to the diarrhea and skin changes that come on with the EGFR TKIs. 

This pattern of side effects is different and requires some additional attention, but with it, the drug can be useful. I’m glad that we have yet another way to fight this disease.

Mark G. Kris, MD, Professor of Medicine, Weill Cornell Medical College; Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York , has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo; Received research grant from: National Institute of Health; Received income in an amount equal to or greater than $250 from: AstraZeneca; Bristol-Myers Squibb; Merck; Daiichi Sankyo Others: Editorial support from Genentech

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

Click to view more from Cancer Data Trends 2025.

Click to view more from Cancer Data Trends 2025.

Click to view more from Cancer Data Trends 2025.