Despite some progress, treatment advancements have lagged for metastatic triple negative breast cancer (mTNBC). New, more effective treatment options for mTNBC are urgently needed.
In this episode of Breast Cancer Breakthroughs, we speak with Komen Scientific Advisory Board member Lisa Newman, M.D., M.P.H.; former Komen grantee, Aditya Bardia, M.D., M.P.H.; and medical oncologist Sarah Sammons, M.D., as they discuss what’s new for those living with mTNBC.
What are the biggest unmet needs for mTNBC?
For many years, chemotherapy was the only treatment option for mTNBC. For Komen Advocate-in-Science member Janice Cowden, chemotherapy was sufficient. She was diagnosed with stage 1 TNBC in 2011 but had a distant recurrence (metastatic breast cancer) in 2016. Amazingly, she experienced a complete response to first-line chemotherapy treatment, where her mTNBC was no longer detectable following treatment, and has had no evidence of disease since that treatment. However, this level of treatment response in metastatic disease is rare.
Treatment options for TNBC have expanded in recent years. In 2018, PARP inhibitors were introduced as a mTNBC treatment option for individuals with a BRCA1 or BRCA2 inherited gene mutation. Immunotherapy was introduced in 2020 for some PD-L1-positive mTNBC. In 2020, the antibody-drug conjugate (ADC) called Trodelvy was added as a treatment option. Although not yet FDA-approved for first-line treatment, ADCs (Trodelvy and Datroway) were just recently added to the National Comprehensive Cancer Network (NCCN) guidelines as a first-line treatment option for mTNBC.
While this progress has brought hope that outcomes will improve for those with mTNBC, Janice believes we can do better.
For the individuals with mTNBC whose tumors are PD-L1-negative, more treatment options are needed. “I see in peer support groups, there are so many of us who are PD-L1-negative, which means no access to immunotherapy,” Janice says. “I think it’s very disappointing for patients to find out that there’s finally something beyond standard of care chemotherapy that could be available and then they don’t qualify.”
Janice also noted the importance of effective first-line treatments to have the best possible outcome. While recent progress has moved the needle for mTNBC — with recent studies showing improvements measured in months, Janice says, “I think that’s one of my biggest hopes is to see some new therapies, or new combinations of existing therapies, give us durable responses for metastatic TNBC in terms of years.”
What does the future hold for treatment of metastatic TNBC?
Janice noted a new class of drugs being tested in clinical trials called bispecifics. “I think the really unique thing about bispecifics is that they’re looking at different targets that haven’t necessarily been explored to full potential for those with metastatic TNBC, and there’s no requirement for some of them to be PD-L1-positive,” she says.
One bispecific drug currently being tested in the ROSETTA Breast-01 clinical trial is called pumitamig or BNT3271. This new bispecific antibody drug targets both PD-L1 and VEGF-A. By targeting PD-L1, the drug is activating the body’s own immune system response against the cancer cells. And, by targeting VEGF-A, it keeps new blood vessels from forming, which starves the cancer cells from vital nutrients and oxygen needed for growth and survival.
Dr. Sammons, a ROSETTA Breast-01 clinical investigator, says “[the drug] pumitamig has the potential to establish a new standard of care immunotherapeutic strategy for patients with PD-L1-negative metastatic TNBC. So, [assuming the Phase 3 trial demonstrates safety and efficacy,] this could be really the first immunotherapy approved for this population, which would be a major win.”
You can hear more about the future of treatments for mTNBC in the episode embedded above.
What are other issues we need to address to improve outcomes for individuals living with mTNBC?
While expanding treatment options is vital for those living with mTNBC, it’s only part of the equation.
Lowering Treatment Toxicities
Treatment side effects, from both existing and new drugs, are a major concern in the breast cancer community, especially for those with metastatic disease. “Because [metastatic] patients are on treatment for life, the majority of them will go from one treatment to another, to another, and over time you get the cumulative side effects”, says Janice. “We don’t want to just live longer, we want to live better.”
Janice continues, “We need evidence that the drug is going to work and provide us with fewer side effects and less toxicities, in particular for those with metastatic breast cancer…and [because the drug is more tolerable] the patient can stay on that drug longer, knowing it’s working.”
Improving Access to Care
Several factors impact access to care including geographic location, socio-economic status and insurance coverage. Janice’s cancer care was impacted by where she lived. She received treatment through a community oncologist, so joining a clinical trial was not an option for her at the time. “My oncologist did not even bring up the idea of a clinical trial,” she says. “But now I have learned so much about the importance of at least discussing clinical trials early on.” So, even if your oncologist doesn’t bring it up, you can ask about clinical trials, no matter where you receive your care.
Addressing Disparities
Black women in the U.S. are twice as likely to be diagnosed with TNBC than white women. Black and Hispanic women are also more likely to face delays in diagnosis, have less access to high-quality care and experience worse outcomes. In fact, a Komen-supported study found that Black women with mTNBC were less likely to receive immunotherapy compared to white women. Furthermore, another recent study showed that black women comprised about 6% of breast cancer clinical trial participants in the U.S. from 2012-2022, when race/ethnicity was reported.
Dr. Newman discusses these disparities in the episode. She offered advice for those currently living with mTNBC, including having a multidisciplinary medical team coordinating your care, not delaying treatment and exploring clinical trial opportunities. “Today, participating in a clinical trial is actually the best way to ensure that an individual is receiving the highest quality care and receiving care that is standardized and monitored extremely closely,” says Dr. Newman. “So, I would say that it’s even more important for racial ethnic minorities to come to an appreciation for the benefits of clinical trial participation.”
Sign up to stay informed about future episodes of Breast Cancer Breakthroughs, we will delve into the most exciting advances in breast cancer treatment and technology coming soon for patients.
Content covered in the Breast Cancer Breakthroughs educational series may be an emerging area in research or technology. This information is being provided for educational purposes only and is not to be construed as medical advice. Talk with your doctor about what is right for you.
For more information on clinical trials or if you need support as you go through treatment, the Komen Patient Care Center can help. Please contact the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465- 6636) or email helpline@komen.org.
Find a clinical trial.
Take this survey to let us know what you think of this content as part of the Breast Cancer Breakthroughs Series.
Explore the ROSETTA Breast01 Trial Fact Sheet.
1 In addition to BNT 327, other codes for pumitamig are BMS986545 or PM8002. Pumitamig is jointly developed by BioNTech and Bristol Myers Squibb.
Breast Cancer Breakthroughs is possible thanks to our series sponsors:
