Breast Cancer

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”

It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.

Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.

Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.

And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.

As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.

Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.

An Ever-Expanding Armamentarium

All of this is telling us how we need to ramp up our game if we are going to be able to use our immune system to quash a cancer. Fortunately, we have abundant and ever-growing capabilities for doing just that.

Immune Checkpoint Inhibitors

The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.

But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.

Therapeutic Cancer Vaccines

There are many therapeutic cancer vaccines in the works, as reviewed in depth here.

Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.

An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.

Antibody-Drug Conjugates (ADC)

There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.

A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.

This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.

Oncolytic Viruses

Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.

After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.

Engineering T Cells (Chimeric Antigen Receptor [CAR-T])

As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.

As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.

Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.

Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.

Summary

Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.

Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.

Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.

Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.

Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.

A version of this article appeared on Medscape.com.

Key clinical point: Nanoparticle albumin‐bound (nab) paclitaxel showed promising clinical activity and tolerable safety in patients with metastatic breast cancer (BC) who were previously treated with taxanes, regardless of their sensitivity or resistance to taxane therapy.

Major finding: The median progression-free survival (PFS) was 7.20 months (95% CI 6.63-7.80 months) for all patients. The median PFS was significantly longer (7.57 vs 4.43 months; P < .001) and the disease control rate was 88.24% vs 68.00% in patients who were taxane-sensitive vs taxane-resistant. Neutropenia (21.19%), leukopenia (19.49%), and sensory neuropathy (6.36%) were the most frequent grade 3-4 adverse events.

Study details: Findings are from a retrospective study including 236 taxane-pretreated women with metastatic BC, of whom 184 were sensitive and 52 were resistant to taxanes based on previous treatment and received nab-paclitaxel as monotherapy or combination therapy.

Disclosures: This study was supported by the Jiangsu Provincial Medical Youth Talent and the Talents Program of Jiangsu Cancer Hospital, China. The authors declared no conflicts of interest.

Source: Xiong W, Xu T, Liu X, Zhang L, Yuan Y. Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients. Cancer. 2024 (Jan 25). doi: 10.1002/cncr.35206 Source

Key clinical point: Nanoparticle albumin‐bound (nab) paclitaxel showed promising clinical activity and tolerable safety in patients with metastatic breast cancer (BC) who were previously treated with taxanes, regardless of their sensitivity or resistance to taxane therapy.

Major finding: The median progression-free survival (PFS) was 7.20 months (95% CI 6.63-7.80 months) for all patients. The median PFS was significantly longer (7.57 vs 4.43 months; P < .001) and the disease control rate was 88.24% vs 68.00% in patients who were taxane-sensitive vs taxane-resistant. Neutropenia (21.19%), leukopenia (19.49%), and sensory neuropathy (6.36%) were the most frequent grade 3-4 adverse events.

Study details: Findings are from a retrospective study including 236 taxane-pretreated women with metastatic BC, of whom 184 were sensitive and 52 were resistant to taxanes based on previous treatment and received nab-paclitaxel as monotherapy or combination therapy.

Disclosures: This study was supported by the Jiangsu Provincial Medical Youth Talent and the Talents Program of Jiangsu Cancer Hospital, China. The authors declared no conflicts of interest.

Source: Xiong W, Xu T, Liu X, Zhang L, Yuan Y. Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients. Cancer. 2024 (Jan 25). doi: 10.1002/cncr.35206 Source

Key clinical point: Nanoparticle albumin‐bound (nab) paclitaxel showed promising clinical activity and tolerable safety in patients with metastatic breast cancer (BC) who were previously treated with taxanes, regardless of their sensitivity or resistance to taxane therapy.

Major finding: The median progression-free survival (PFS) was 7.20 months (95% CI 6.63-7.80 months) for all patients. The median PFS was significantly longer (7.57 vs 4.43 months; P < .001) and the disease control rate was 88.24% vs 68.00% in patients who were taxane-sensitive vs taxane-resistant. Neutropenia (21.19%), leukopenia (19.49%), and sensory neuropathy (6.36%) were the most frequent grade 3-4 adverse events.

Study details: Findings are from a retrospective study including 236 taxane-pretreated women with metastatic BC, of whom 184 were sensitive and 52 were resistant to taxanes based on previous treatment and received nab-paclitaxel as monotherapy or combination therapy.

Disclosures: This study was supported by the Jiangsu Provincial Medical Youth Talent and the Talents Program of Jiangsu Cancer Hospital, China. The authors declared no conflicts of interest.

Source: Xiong W, Xu T, Liu X, Zhang L, Yuan Y. Efficacy and safety of nanoparticle albumin-bound paclitaxel in taxane-pretreated metastatic breast cancer patients. Cancer. 2024 (Jan 25). doi: 10.1002/cncr.35206 Source

Key clinical point: Poziotinib demonstrated promising antitumor activity but high toxicity in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC) who were heavily pretreated with HER2-directed therapy.

Major finding: Intermittent and continuous dosing schedules of poziotinib led to objective response rates of 30% each (P = .98) and disease control rates of 60% and 78% (P = .15), respectively. Grades 3-4 treatment-related adverse events were reported by 67% and 76% of patients receiving intermittent and continuous dosing schedules of poziotinib, respectively.

Study details: This phase 2 trial included 67 patients with HER2+ advanced BC who were previously treated with two or more HER2-directed regimens and who received 24 mg poziotinib once daily on an intermittent dosing schedule (n = 33) or 16 mg poziotinib once daily on a continuous dosing schedule (n = 34).

Disclosures: This study received financial support from Spectrum Pharmaceuticals. Gajanan Bhat and Szu-Yun Leu declared being employees of Spectrum Pharmaceuticals. Adam Brufsky declared serving as a consultant for and receiving research support from various sources. The other authors did not declare any conflicts of interest.

Source: Nasrazadani A, Marti JLG, Lathrop K, et al. Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens. Breast Cancer Res Treat. 2024 (Jan 23). doi: 10.1007/s10549-023-07236-z  Source

Key clinical point: Poziotinib demonstrated promising antitumor activity but high toxicity in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC) who were heavily pretreated with HER2-directed therapy.

Major finding: Intermittent and continuous dosing schedules of poziotinib led to objective response rates of 30% each (P = .98) and disease control rates of 60% and 78% (P = .15), respectively. Grades 3-4 treatment-related adverse events were reported by 67% and 76% of patients receiving intermittent and continuous dosing schedules of poziotinib, respectively.

Study details: This phase 2 trial included 67 patients with HER2+ advanced BC who were previously treated with two or more HER2-directed regimens and who received 24 mg poziotinib once daily on an intermittent dosing schedule (n = 33) or 16 mg poziotinib once daily on a continuous dosing schedule (n = 34).

Disclosures: This study received financial support from Spectrum Pharmaceuticals. Gajanan Bhat and Szu-Yun Leu declared being employees of Spectrum Pharmaceuticals. Adam Brufsky declared serving as a consultant for and receiving research support from various sources. The other authors did not declare any conflicts of interest.

Source: Nasrazadani A, Marti JLG, Lathrop K, et al. Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens. Breast Cancer Res Treat. 2024 (Jan 23). doi: 10.1007/s10549-023-07236-z  Source

Key clinical point: Poziotinib demonstrated promising antitumor activity but high toxicity in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced breast cancer (BC) who were heavily pretreated with HER2-directed therapy.

Major finding: Intermittent and continuous dosing schedules of poziotinib led to objective response rates of 30% each (P = .98) and disease control rates of 60% and 78% (P = .15), respectively. Grades 3-4 treatment-related adverse events were reported by 67% and 76% of patients receiving intermittent and continuous dosing schedules of poziotinib, respectively.

Study details: This phase 2 trial included 67 patients with HER2+ advanced BC who were previously treated with two or more HER2-directed regimens and who received 24 mg poziotinib once daily on an intermittent dosing schedule (n = 33) or 16 mg poziotinib once daily on a continuous dosing schedule (n = 34).

Disclosures: This study received financial support from Spectrum Pharmaceuticals. Gajanan Bhat and Szu-Yun Leu declared being employees of Spectrum Pharmaceuticals. Adam Brufsky declared serving as a consultant for and receiving research support from various sources. The other authors did not declare any conflicts of interest.

Source: Nasrazadani A, Marti JLG, Lathrop K, et al. Poziotinib treatment in patients with HER2-positive advanced breast cancer who have received prior anti-HER2 regimens. Breast Cancer Res Treat. 2024 (Jan 23). doi: 10.1007/s10549-023-07236-z  Source

Key clinical point: Both hypofractionated (HF) and conventional fractionated (CF) radiotherapy were comparably effective in patients who had undergone surgery for breast cancer (BC); however, the HF vs CF regimen was more effective in reducing skin toxicity and relieving fatigue.

Major finding: CF vs HF radiotherapy demonstrated no significant improvement in terms of local recurrence (odds ratio [OR] 0.91; P  =  .30) or overall survival (OR 1.08; P  =  .28) outcomes. Although safety outcomes like breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity were comparable in both groups, HF vs CF regimen led to lower skin toxicity (OR 0.43; P < .01) and improved patient fatigue outcomes (OR 0.73; P < .01).

Study details: This meta-analysis of 35 studies included 18,246 patients diagnosed with BC who underwent surgery and were treated with HF or CF radiotherapy.

Disclosures: This study was supported by the Key Research and Development Projects of Shaanxi Province, China, and other sources. The authors declared no conflicts of interest.

Source: Lu Y, Hui B, Yang D, et al. Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients. BMC Cancer. 2024;24:181. doi: 10.1186/s12885-024-11918-2  Source

Key clinical point: Both hypofractionated (HF) and conventional fractionated (CF) radiotherapy were comparably effective in patients who had undergone surgery for breast cancer (BC); however, the HF vs CF regimen was more effective in reducing skin toxicity and relieving fatigue.

Major finding: CF vs HF radiotherapy demonstrated no significant improvement in terms of local recurrence (odds ratio [OR] 0.91; P  =  .30) or overall survival (OR 1.08; P  =  .28) outcomes. Although safety outcomes like breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity were comparable in both groups, HF vs CF regimen led to lower skin toxicity (OR 0.43; P < .01) and improved patient fatigue outcomes (OR 0.73; P < .01).

Study details: This meta-analysis of 35 studies included 18,246 patients diagnosed with BC who underwent surgery and were treated with HF or CF radiotherapy.

Disclosures: This study was supported by the Key Research and Development Projects of Shaanxi Province, China, and other sources. The authors declared no conflicts of interest.

Source: Lu Y, Hui B, Yang D, et al. Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients. BMC Cancer. 2024;24:181. doi: 10.1186/s12885-024-11918-2  Source

Key clinical point: Both hypofractionated (HF) and conventional fractionated (CF) radiotherapy were comparably effective in patients who had undergone surgery for breast cancer (BC); however, the HF vs CF regimen was more effective in reducing skin toxicity and relieving fatigue.

Major finding: CF vs HF radiotherapy demonstrated no significant improvement in terms of local recurrence (odds ratio [OR] 0.91; P  =  .30) or overall survival (OR 1.08; P  =  .28) outcomes. Although safety outcomes like breast pain, breast atrophy, lymphedema, pneumonia, pulmonary fibrosis, telangiectasia, and cardiotoxicity were comparable in both groups, HF vs CF regimen led to lower skin toxicity (OR 0.43; P < .01) and improved patient fatigue outcomes (OR 0.73; P < .01).

Study details: This meta-analysis of 35 studies included 18,246 patients diagnosed with BC who underwent surgery and were treated with HF or CF radiotherapy.

Disclosures: This study was supported by the Key Research and Development Projects of Shaanxi Province, China, and other sources. The authors declared no conflicts of interest.

Source: Lu Y, Hui B, Yang D, et al. Efficacy and safety analysis of hypofractionated and conventional fractionated radiotherapy in postoperative breast cancer patients. BMC Cancer. 2024;24:181. doi: 10.1186/s12885-024-11918-2  Source

Key clinical point: Compared with patients having metaplastic breast cancer (MpBC) who did not receive any chemotherapy, prognostic outcomes were significantly improved in those who received neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy.

Major finding: Compared with patients who did not receive any chemotherapy, the overall survival (OS) improved significantly in those who received adjuvant chemotherapy (hazard ratio [HR] 0.451; P < .001) or responded to NAC (HR 0.479; P < .001). Breast cancer-specific survival also improved in patients who received and responded to NAC or received adjuvant chemotherapy.

Study details: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database and included 1186 patients with MpBC who received NAC (n = 181), adjuvant chemotherapy (n = 647), or did not receive any chemotherapy (n = 358).

Disclosures: This study was supported by the Science and Technology Innovation Plan of Shanghai Science and Technology Commission and the Obstetrics and Gynecology Hospital of Fudan University. The authors declared no conflicts of interest.

Source: Zhang M, Yuan J, Wang M, Zhang M, Chen H. Chemotherapy is of prognostic significance to metaplastic breast cancer. Sci Rep. 2024;14:1210. doi: 10.1038/s41598-024-51627-1 Source

Key clinical point: Compared with patients having metaplastic breast cancer (MpBC) who did not receive any chemotherapy, prognostic outcomes were significantly improved in those who received neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy.

Major finding: Compared with patients who did not receive any chemotherapy, the overall survival (OS) improved significantly in those who received adjuvant chemotherapy (hazard ratio [HR] 0.451; P < .001) or responded to NAC (HR 0.479; P < .001). Breast cancer-specific survival also improved in patients who received and responded to NAC or received adjuvant chemotherapy.

Study details: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database and included 1186 patients with MpBC who received NAC (n = 181), adjuvant chemotherapy (n = 647), or did not receive any chemotherapy (n = 358).

Disclosures: This study was supported by the Science and Technology Innovation Plan of Shanghai Science and Technology Commission and the Obstetrics and Gynecology Hospital of Fudan University. The authors declared no conflicts of interest.

Source: Zhang M, Yuan J, Wang M, Zhang M, Chen H. Chemotherapy is of prognostic significance to metaplastic breast cancer. Sci Rep. 2024;14:1210. doi: 10.1038/s41598-024-51627-1 Source

Key clinical point: Compared with patients having metaplastic breast cancer (MpBC) who did not receive any chemotherapy, prognostic outcomes were significantly improved in those who received neoadjuvant chemotherapy (NAC) or adjuvant chemotherapy.

Major finding: Compared with patients who did not receive any chemotherapy, the overall survival (OS) improved significantly in those who received adjuvant chemotherapy (hazard ratio [HR] 0.451; P < .001) or responded to NAC (HR 0.479; P < .001). Breast cancer-specific survival also improved in patients who received and responded to NAC or received adjuvant chemotherapy.

Study details: This study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database and included 1186 patients with MpBC who received NAC (n = 181), adjuvant chemotherapy (n = 647), or did not receive any chemotherapy (n = 358).

Disclosures: This study was supported by the Science and Technology Innovation Plan of Shanghai Science and Technology Commission and the Obstetrics and Gynecology Hospital of Fudan University. The authors declared no conflicts of interest.

Source: Zhang M, Yuan J, Wang M, Zhang M, Chen H. Chemotherapy is of prognostic significance to metaplastic breast cancer. Sci Rep. 2024;14:1210. doi: 10.1038/s41598-024-51627-1 Source

Key clinical point: Patients with early-stage triple-negative breast cancer (TNBC) should receive adjuvant chemotherapy without unnecessary delays after primary surgery because prognosis may worsen if treatment is postponed beyond 6 weeks.

Major finding: Patients who received adjuvant systemic therapy within 22-28 days after surgery reported the most favorable overall survival (OS) outcomes (median OS 10.2 years), with the OS decreasing in the groups that received adjuvant systemic therapy during 29-35 days, 36-42 days, and >6 weeks after surgery (8.3 years, 7.8 years, and 6.9 years, respectively).

Study details: Findings are from a retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after primary surgery.

Disclosures: The open access funding for this study was enabled and organized by Projekt DEAL. Some authors declared receiving honoraria or travel reimbursements from or serving as consultants or board members for various sources.

Source: Hatzipanagiotou ME, Pigerl M, Gerken M, et al. Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer. Breast Cancer Res Treat. 2024 (Jan 19). doi: 10.1007/s10549-023-07207-4 Source

Key clinical point: Patients with early-stage triple-negative breast cancer (TNBC) should receive adjuvant chemotherapy without unnecessary delays after primary surgery because prognosis may worsen if treatment is postponed beyond 6 weeks.

Major finding: Patients who received adjuvant systemic therapy within 22-28 days after surgery reported the most favorable overall survival (OS) outcomes (median OS 10.2 years), with the OS decreasing in the groups that received adjuvant systemic therapy during 29-35 days, 36-42 days, and >6 weeks after surgery (8.3 years, 7.8 years, and 6.9 years, respectively).

Study details: Findings are from a retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after primary surgery.

Disclosures: The open access funding for this study was enabled and organized by Projekt DEAL. Some authors declared receiving honoraria or travel reimbursements from or serving as consultants or board members for various sources.

Source: Hatzipanagiotou ME, Pigerl M, Gerken M, et al. Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer. Breast Cancer Res Treat. 2024 (Jan 19). doi: 10.1007/s10549-023-07207-4 Source

Key clinical point: Patients with early-stage triple-negative breast cancer (TNBC) should receive adjuvant chemotherapy without unnecessary delays after primary surgery because prognosis may worsen if treatment is postponed beyond 6 weeks.

Major finding: Patients who received adjuvant systemic therapy within 22-28 days after surgery reported the most favorable overall survival (OS) outcomes (median OS 10.2 years), with the OS decreasing in the groups that received adjuvant systemic therapy during 29-35 days, 36-42 days, and >6 weeks after surgery (8.3 years, 7.8 years, and 6.9 years, respectively).

Study details: Findings are from a retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after primary surgery.

Disclosures: The open access funding for this study was enabled and organized by Projekt DEAL. Some authors declared receiving honoraria or travel reimbursements from or serving as consultants or board members for various sources.

Source: Hatzipanagiotou ME, Pigerl M, Gerken M, et al. Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer. Breast Cancer Res Treat. 2024 (Jan 19). doi: 10.1007/s10549-023-07207-4 Source

Key clinical point: Addition of veliparib vs placebo to carboplatin + paclitaxel did not significantly improve the overall survival (OS) outcomes in patients with BRCA1/2-mutated human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A combination of veliparib and carboplatin + paclitaxel vs placebo + carboplatin + paclitaxel led to numerical but nonsignificant improvements in median OS (32.4 vs 28.2 months; hazard ratio 0.916; P = .434). The addition of veliparib was generally well-tolerated, consistent with previous findings.

Study details: Findings are from the phase 3 BROCADE3 trial which included 509 patients with BRCA1/2-mutated HER2− advanced BC who had received at least two prior lines of chemotherapy and were randomly assigned to receive carboplatin + paclitaxel with either veliparib or placebo.

Disclosures: This study was funded by AbbVie. No other disclosures were reported in this study.

Source: Diéras V, Han HS, Wildiers H, et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024;200:113580. doi: 10.1016/j.ejca.2024.113580 Source

Key clinical point: Addition of veliparib vs placebo to carboplatin + paclitaxel did not significantly improve the overall survival (OS) outcomes in patients with BRCA1/2-mutated human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A combination of veliparib and carboplatin + paclitaxel vs placebo + carboplatin + paclitaxel led to numerical but nonsignificant improvements in median OS (32.4 vs 28.2 months; hazard ratio 0.916; P = .434). The addition of veliparib was generally well-tolerated, consistent with previous findings.

Study details: Findings are from the phase 3 BROCADE3 trial which included 509 patients with BRCA1/2-mutated HER2− advanced BC who had received at least two prior lines of chemotherapy and were randomly assigned to receive carboplatin + paclitaxel with either veliparib or placebo.

Disclosures: This study was funded by AbbVie. No other disclosures were reported in this study.

Source: Diéras V, Han HS, Wildiers H, et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024;200:113580. doi: 10.1016/j.ejca.2024.113580 Source

Key clinical point: Addition of veliparib vs placebo to carboplatin + paclitaxel did not significantly improve the overall survival (OS) outcomes in patients with BRCA1/2-mutated human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (BC).

Major finding: A combination of veliparib and carboplatin + paclitaxel vs placebo + carboplatin + paclitaxel led to numerical but nonsignificant improvements in median OS (32.4 vs 28.2 months; hazard ratio 0.916; P = .434). The addition of veliparib was generally well-tolerated, consistent with previous findings.

Study details: Findings are from the phase 3 BROCADE3 trial which included 509 patients with BRCA1/2-mutated HER2− advanced BC who had received at least two prior lines of chemotherapy and were randomly assigned to receive carboplatin + paclitaxel with either veliparib or placebo.

Disclosures: This study was funded by AbbVie. No other disclosures were reported in this study.

Source: Diéras V, Han HS, Wildiers H, et al. Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): Final overall survival results from a randomized phase 3 trial. Eur J Cancer. 2024;200:113580. doi: 10.1016/j.ejca.2024.113580 Source

Key clinical point: Treatment with toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel significantly improved progression-free survival (PFS) and showed an acceptable safety profile in patients with programmed death ligand-1 (PD-L1)-positive metastatic or recurrent triple-negative breast cancer (TNBC).

Major finding: Toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel led to a significantly longer PFS (median 8.4 vs 5.6 months) in patients with PD-L1-positive TNBC (hazard ratio 0.65; P = .0102) and similar incidences of grade ≥3 treatment-emergent adverse events (56.4% vs 54.3%) and fatal adverse events (0.6% vs 3.4%).

Study details: Findings are from the phase 3 TORCHLIGHT trial which included 531 patients with metastatic or recurrent locally advanced TNBC who were previously untreated or treated with up to one systemic chemotherapy and were randomly assigned to receive toripalimab + nab-paclitaxel or placebo + nab-paclitaxel. Of these, 300 patients had PD-L1-positive TNBC.

Disclosures: This study was sponsored by Shanghai Junshi Biosciences and supported by other sources. Five authors declared being employees of Shanghai Junshi Biosciences or TopAlliance Biosciences. The other authors declared no competing interests.

Source: Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: A randomized phase 3 trial. Nat Med. 2024;30:249-256. doi: 10.1038/s41591-023-02677-x Source

Key clinical point: Treatment with toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel significantly improved progression-free survival (PFS) and showed an acceptable safety profile in patients with programmed death ligand-1 (PD-L1)-positive metastatic or recurrent triple-negative breast cancer (TNBC).

Major finding: Toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel led to a significantly longer PFS (median 8.4 vs 5.6 months) in patients with PD-L1-positive TNBC (hazard ratio 0.65; P = .0102) and similar incidences of grade ≥3 treatment-emergent adverse events (56.4% vs 54.3%) and fatal adverse events (0.6% vs 3.4%).

Study details: Findings are from the phase 3 TORCHLIGHT trial which included 531 patients with metastatic or recurrent locally advanced TNBC who were previously untreated or treated with up to one systemic chemotherapy and were randomly assigned to receive toripalimab + nab-paclitaxel or placebo + nab-paclitaxel. Of these, 300 patients had PD-L1-positive TNBC.

Disclosures: This study was sponsored by Shanghai Junshi Biosciences and supported by other sources. Five authors declared being employees of Shanghai Junshi Biosciences or TopAlliance Biosciences. The other authors declared no competing interests.

Source: Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: A randomized phase 3 trial. Nat Med. 2024;30:249-256. doi: 10.1038/s41591-023-02677-x Source

Key clinical point: Treatment with toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel significantly improved progression-free survival (PFS) and showed an acceptable safety profile in patients with programmed death ligand-1 (PD-L1)-positive metastatic or recurrent triple-negative breast cancer (TNBC).

Major finding: Toripalimab + nab-paclitaxel vs placebo + nab-paclitaxel led to a significantly longer PFS (median 8.4 vs 5.6 months) in patients with PD-L1-positive TNBC (hazard ratio 0.65; P = .0102) and similar incidences of grade ≥3 treatment-emergent adverse events (56.4% vs 54.3%) and fatal adverse events (0.6% vs 3.4%).

Study details: Findings are from the phase 3 TORCHLIGHT trial which included 531 patients with metastatic or recurrent locally advanced TNBC who were previously untreated or treated with up to one systemic chemotherapy and were randomly assigned to receive toripalimab + nab-paclitaxel or placebo + nab-paclitaxel. Of these, 300 patients had PD-L1-positive TNBC.

Disclosures: This study was sponsored by Shanghai Junshi Biosciences and supported by other sources. Five authors declared being employees of Shanghai Junshi Biosciences or TopAlliance Biosciences. The other authors declared no competing interests.

Source: Jiang Z, Ouyang Q, Sun T, et al. Toripalimab plus nab-paclitaxel in metastatic or recurrent triple-negative breast cancer: A randomized phase 3 trial. Nat Med. 2024;30:249-256. doi: 10.1038/s41591-023-02677-x Source

Key clinical point: In patients with platinum-pretreated advanced triple-negative breast cancer (TNBC), a chemotherapy-free maintenance regimen containing olaparib with or without durvalumab vs continued platinum-based chemotherapy led to a greater improvement in progression-free survival (PFS) with no new safety signals.

Major finding: The median PFS was 4.0 months with olaparib and 6.1 months with olaparib + durvalumab, with both treatments providing greater PFS benefit than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). No treatment-related deaths or new safety signals were reported.

Study details: Findings are from the phase 2 DORA trial which included 45 patients with advanced TNBC who had stable disease or complete or partial response after receiving platinum-based chemotherapy and were randomly assigned to receive olaparib or olaparib + durvalumab.

Disclosures: This study was supported by AstraZeneca Pharmaceuticals LP. Some authors declared receiving honoraria, research funding, or fees; owning stocks; or having other ties with AstraZeneca and various other sources.

Source: Tan TJ, Sammons S, Im YH, et al. Phase II DORA study of olaparib with or without durvalumab as a chemotherapy-free maintenance strategy in platinum-pretreated advanced triple-negative breast cancer. Clin Cancer Res. 2024 (Jan 18). doi: 10.1158/1078-0432.CCR-23-2513 Source

Key clinical point: In patients with platinum-pretreated advanced triple-negative breast cancer (TNBC), a chemotherapy-free maintenance regimen containing olaparib with or without durvalumab vs continued platinum-based chemotherapy led to a greater improvement in progression-free survival (PFS) with no new safety signals.

Major finding: The median PFS was 4.0 months with olaparib and 6.1 months with olaparib + durvalumab, with both treatments providing greater PFS benefit than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). No treatment-related deaths or new safety signals were reported.

Study details: Findings are from the phase 2 DORA trial which included 45 patients with advanced TNBC who had stable disease or complete or partial response after receiving platinum-based chemotherapy and were randomly assigned to receive olaparib or olaparib + durvalumab.

Disclosures: This study was supported by AstraZeneca Pharmaceuticals LP. Some authors declared receiving honoraria, research funding, or fees; owning stocks; or having other ties with AstraZeneca and various other sources.

Source: Tan TJ, Sammons S, Im YH, et al. Phase II DORA study of olaparib with or without durvalumab as a chemotherapy-free maintenance strategy in platinum-pretreated advanced triple-negative breast cancer. Clin Cancer Res. 2024 (Jan 18). doi: 10.1158/1078-0432.CCR-23-2513 Source

Key clinical point: In patients with platinum-pretreated advanced triple-negative breast cancer (TNBC), a chemotherapy-free maintenance regimen containing olaparib with or without durvalumab vs continued platinum-based chemotherapy led to a greater improvement in progression-free survival (PFS) with no new safety signals.

Major finding: The median PFS was 4.0 months with olaparib and 6.1 months with olaparib + durvalumab, with both treatments providing greater PFS benefit than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). No treatment-related deaths or new safety signals were reported.

Study details: Findings are from the phase 2 DORA trial which included 45 patients with advanced TNBC who had stable disease or complete or partial response after receiving platinum-based chemotherapy and were randomly assigned to receive olaparib or olaparib + durvalumab.

Disclosures: This study was supported by AstraZeneca Pharmaceuticals LP. Some authors declared receiving honoraria, research funding, or fees; owning stocks; or having other ties with AstraZeneca and various other sources.

Source: Tan TJ, Sammons S, Im YH, et al. Phase II DORA study of olaparib with or without durvalumab as a chemotherapy-free maintenance strategy in platinum-pretreated advanced triple-negative breast cancer. Clin Cancer Res. 2024 (Jan 18). doi: 10.1158/1078-0432.CCR-23-2513 Source

Key clinical point: Neoadjuvant endocrine therapy with fulvestrant or anastrozole + fulvestrant led to an endocrine-sensitive disease rate (ESDR) comparable to anastrozole alone in postmenopausal women with estrogen receptor (ER)-rich, human epidermal growth factor receptor 2-negative (ERBB2−) breast cancer (BC).

Major finding: Both fulvestrant and anastrozole + fulvestrant vs anastrozole alone demonstrated no significant improvement in the ESDR at 6 months (22.8% and 20.5% vs 18.7%, respectively; Wald test, P ≥ .98) and median percentage change in Ki67 at 4 weeks (−79.1% and −83.5% vs −80.6%, respectively; P ≥ .15).

Study details: Findings are from the phase 3 ALTERNATE trial, which included 1298 treatment-naive postmenopausal women with ER-rich/ERBB2− BC who were randomly assigned to receive anastrozole, fulvestrant, or anastrozole + fulvestrant for 6 months in a neoadjuvant setting.

Disclosures: This study was supported by the US National Institutes of Health (NIH)/National Cancer Institute (NCI) and other sources. Several authors declared receiving grants, personal fees, or research support or having other ties with various sources, including NIH/NCI.

Source: Ma CX, Suman VJ, Sanati S, et al. Endocrine-sensitive disease rate in postmenopausal patients with estrogen receptor-rich/ERBB2-negative breast cancer receiving neoadjuvant anastrozole, fulvestrant, or their combination: A phase 3 randomized clinical trial. JAMA Oncol. 2024 (Jan 18). doi: 10.1001/jamaoncol.2023.6038  Source

Key clinical point: Neoadjuvant endocrine therapy with fulvestrant or anastrozole + fulvestrant led to an endocrine-sensitive disease rate (ESDR) comparable to anastrozole alone in postmenopausal women with estrogen receptor (ER)-rich, human epidermal growth factor receptor 2-negative (ERBB2−) breast cancer (BC).

Major finding: Both fulvestrant and anastrozole + fulvestrant vs anastrozole alone demonstrated no significant improvement in the ESDR at 6 months (22.8% and 20.5% vs 18.7%, respectively; Wald test, P ≥ .98) and median percentage change in Ki67 at 4 weeks (−79.1% and −83.5% vs −80.6%, respectively; P ≥ .15).

Study details: Findings are from the phase 3 ALTERNATE trial, which included 1298 treatment-naive postmenopausal women with ER-rich/ERBB2− BC who were randomly assigned to receive anastrozole, fulvestrant, or anastrozole + fulvestrant for 6 months in a neoadjuvant setting.

Disclosures: This study was supported by the US National Institutes of Health (NIH)/National Cancer Institute (NCI) and other sources. Several authors declared receiving grants, personal fees, or research support or having other ties with various sources, including NIH/NCI.

Source: Ma CX, Suman VJ, Sanati S, et al. Endocrine-sensitive disease rate in postmenopausal patients with estrogen receptor-rich/ERBB2-negative breast cancer receiving neoadjuvant anastrozole, fulvestrant, or their combination: A phase 3 randomized clinical trial. JAMA Oncol. 2024 (Jan 18). doi: 10.1001/jamaoncol.2023.6038  Source

Key clinical point: Neoadjuvant endocrine therapy with fulvestrant or anastrozole + fulvestrant led to an endocrine-sensitive disease rate (ESDR) comparable to anastrozole alone in postmenopausal women with estrogen receptor (ER)-rich, human epidermal growth factor receptor 2-negative (ERBB2−) breast cancer (BC).

Major finding: Both fulvestrant and anastrozole + fulvestrant vs anastrozole alone demonstrated no significant improvement in the ESDR at 6 months (22.8% and 20.5% vs 18.7%, respectively; Wald test, P ≥ .98) and median percentage change in Ki67 at 4 weeks (−79.1% and −83.5% vs −80.6%, respectively; P ≥ .15).

Study details: Findings are from the phase 3 ALTERNATE trial, which included 1298 treatment-naive postmenopausal women with ER-rich/ERBB2− BC who were randomly assigned to receive anastrozole, fulvestrant, or anastrozole + fulvestrant for 6 months in a neoadjuvant setting.

Disclosures: This study was supported by the US National Institutes of Health (NIH)/National Cancer Institute (NCI) and other sources. Several authors declared receiving grants, personal fees, or research support or having other ties with various sources, including NIH/NCI.

Source: Ma CX, Suman VJ, Sanati S, et al. Endocrine-sensitive disease rate in postmenopausal patients with estrogen receptor-rich/ERBB2-negative breast cancer receiving neoadjuvant anastrozole, fulvestrant, or their combination: A phase 3 randomized clinical trial. JAMA Oncol. 2024 (Jan 18). doi: 10.1001/jamaoncol.2023.6038  Source