Dr Lynce on Ongoing Trials Evaluating Novel Combinations in Inflammatory Breast Cancer 

Filipa Lynce, MD, senior physician, director, Inflammatory Breast Cancer Program, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses 2 ongoing clinical trials investigating novel therapeutic combinations for the treatment of patients with inflammatory breast cancer.

First, Lynce highlights the phase 2 TRUDI trial (NCT05795101), which is enrolling patients with stage III HER2-positive and HER2-low inflammatory breast cancer. Patients are being treated with the neoadjuvant combination of fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and durvalumab (Imfinzi). Patients are allowed to have hormone receptor (HR)–positive or –negative disease; however, this must be known at enrollment. The combination of T-DXd and durvalumab is being given once every 3 weeks for up to 8 cycles prior to surgery. The trial is actively enrolling patients at both Dana-Farber Cancer Institute and MD Anderson Cancer Center, Lynce says.

Lynce also mentions cohort C of the phase 2 NeoSTAR trial (NCT04230109), which is specifically enrolling patients with HER2-negative inflammatory breast cancer, including those with HR-positive, HER2-negative and triple-negative subtypes. In this study, patients are receiving neoadjuvant treatment with sacituzumab govitecan-hziy (Trodelvy) along or in combination with pembrolizumab (Keytruda) for up to 4 cycles. Treatment is allowed to by followed by chemotherapy at the discretion of the treating physician. Lynce notes that this study could help determine if substituting paclitaxel with sacituzumab govitecan can yield better outcomes in a high-risk population.

As these trials continue to evolve, Lynce emphasizes the critical need for more dedicated clinical trials or specific cohorts within larger studies to accurately assess the efficacy of novel treatments for patients with inflammatory breast cancer. These focused investigations are essential to understanding the unique responses of patients with inflammatory breast cancer to existing and emerging therapies, thereby allowing the tailoring of future treatment strategies to improve their prognosis and quality of life, she concludes.

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Filipa Lynce, MD, discusses ongoing clinical trials investigating novel combinations in patients with inflammatory breast cancer.

Dr Lynce on the Prognosis of Patients With Inflammatory Breast Cancer

Filipa Lynce, MD senior physician, director, Inflammatory Breast Cancer Program, Dana-Farber Cancer Institute; assistant professor, medicine, Harvard Medical School, discusses the current prognosis of patients diagnosed with inflammatory breast cancer (IBC) and highlights the need for more effective treatment options in this disease setting.

Historically, outcomes for patients with IBC are poor compared with those of patients displaying other forms of locally advanced breast cancer, Lynce begins. However, overall improvements in breast cancer management have led to better outcomes for patients with IBC. Despite these advances, IBC remains a particularly difficult-to-treat type of breast cancer due to its aggressive nature and distinct clinical behavior.

Lynce emphasizes the importance of considering the subtype of IBC when evaluating patient prognosis. Not all IBC cases are the same, as a patient’s subtype significantly influences their response to treatment and overall outcomes, Lynce explains. For example, patients with HER2-positive IBC tend to respond well to HER2-targeted therapies, Lynce notes. The development and refinement of these targeted therapies have substantially improved survival rates for patients with this disease subtype.

Conversely, triple-negative IBC (TN-IBC) is highly aggressive and is associated with worse outcomes relative to other IBC subtypes, Lynce says, adding that patient prognosis is often worse than that of triple-negative breast cancer in general, Lynce explains. The aggressive nature of TN-IBC and the limited treatment arsenal for this subtype contribute to poorer outcomes, highlighting a critical area of unmet need.

Lynce underscores the need for ongoing research and the development of new targeted therapies within this space, particularly for challenging subtypes like TN-IBC. Personalized treatment strategies based on the molecular characteristics of these tumors are crucial for improving outcomes.

Overall, the exploration of new therapeutic agents and combination regimens tailored to the specific biology of IBC subtypes may enhance patient prognosis and quality of life, Lynce conclude

Filipa Lynce, MD, discusses the current prognosis of patients diagnosed with inflammatory breast cancer subtypes. 

Filipa Lynce, MD, medical oncologist at MedStar Washington Hospital Center and Lombardi Comprehensive Cancer Center and an assistant professor of medicine at Georgetown University, discusses remaining questions regarding the use of PARP inhibitors in breast cancer.

More information regarding the use of PARP inhibitors in breast cancer continues to emerge as more research is conducted, says Lynce. Notably, olaparib (Lynparza) received FDA approval for use in patients with HER2-negative metastatic breast cancers that harbor germline 

mutations and talazoparib (Talzenna) received regulatory approval for use in patients with deleterious or suspected deleterious germline 

-mutated HER2-negative, locally advanced or metastatic disease, adds Lynce.

Ongoing research efforts are dedicated to understanding whether the efficacy of PARP inhibitors in patients with these germline mutations can be increased by combining these agents with other drugs, such as immunotherapy. Other efforts are examining whether PARP inhibitor combinations can also have a role in the treatment of those without germline mutations, says Lynce.

Questions remain regarding how to sequence these drugs, adds Lynce. Should they be used in the first-line setting? As single agents? In the maintenance setting? Interesting data have recently been reported with PARP inhibitors in combination with immunotherapy, says Lynce. Future research will focus on examining the utility of these agents in the maintenance setting, concludes Lynce.

Filipa Lynce, MD, discusses remaining questions regarding the use of PARP inhibitors in breast cancer.

Dr. Lynce on Remaining Questions With PARP Inhibitors in Breast Cancer

Filipa Lynce, MD, medical oncologist, MedStar Washington Hospital Center and Lombardi Comprehensive Cancer Center, and assistant professor of medicine, Georgetown University, discusses the FDA approval of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) for the frontline treatment of patients with unresectable locally advanced or metastatic PD-L1—positive triple-negative breast cancer (TNBC).

In March 2019, the combination was granted accelerated approval based on findings from the phase III IMpassion130 trial, explains Lynce. Results of the trial demonstrated a 40% reduction in the risk of disease progression or death compared with nab-paclitaxel alone.

Though this regimen is being utilized in the clinic, clinical trials should be considered for patients when possible to allow more combination strategies to emerge in this space, concludes Lynce.

Filipa Lynce, MD, discusses the FDA approval of atezolizumab plus nab-paclitaxel for the frontline treatment of patients with unresectable locally advanced or metastatic PD-L1

Dr. Lynce on FDA Approval of Atezolizumab/Nab-Paclitaxel in TNBC

Only by the end of my first year of fellowship did I realize that beyond your fellowship experience there is a lot you can gain. Learning how to take care of our patients is definitely very important, but there is much more that we can gain from this period of our lives, specifically in terms of our learning. Whether you foresee a career in academia, private practice, or industry, there are opportunities available to you during this time period that will not be repeated.

It was after several conversations, looking over different curriculum vitaes, and spending endless hours surfing on the Internet that I learned most of the things I will share with you. Given my strong interest in breast cancer, my focus will be mainly on oncology, but similar opportunities are out there for those who are passionate about hematology or other solid malignancies as well.

During your fellowship experience, an amazing opportunity is to participate in writing a study protocol from beginning to end. This includes beginning with a discussion of the idea, writing a letter of intent (LOI) and submitting it for peer review, receiving funding, writing the whole protocol, getting institutional review board (IRB) approval, opening the study, enrolling patients, and hopefully, beginning to see results before you graduate!

The most difficult step may be finding an original concept and the appropriate mentoring in your institution for helpful, guiding expertise. Behind that is writing your LOI and perhaps submitting it to a workshop where your idea can be further developed.

For fellows and junior faculty, one of the most amazing experiences in clinical cancer research is attending the ASCO/AACR Vail Workshop that occurs every year during the summer season. The workshop includes 100 “students” with diverse backgrounds (medical oncology, radiation oncology, hematology, gynecology oncology, neuro-oncology, surgical oncology, and pediatrics) and a world-class faculty devoted to the students for a whole week.

The faculty includes outstanding clinical and transla- tional researchers, phase 1 experts, past and current American Society of Clinical Oncology (ASCO) presidents, biostatisticians, and patient advocates. The workshop is quite competitive, and if you are considering the use of an investigational drug provided by a pharmaceutical company, you need a commitment letter, so start working on it early. It will be worth it!

The American Society of Hematology (ASH) also has opportunities such as the Translational Research Training in Hematology Program to help you develop your own protocol.

The National Institutes of Health has several fellowship (F) and Career Development (K) awards that are worth exploring (http://grants.nih.gov/training/extramural.htm or http://www.cancer.gov/researchandfunding/cancertraining).

These are highly competitive but very prestigious awards to start your career with.

Another possible funding source for a fellow is the ASCO organization. In response to a need to recruit promising investigators into academic medicine, ASCO created the Young Investigator Award (YIA). In 1984, ASCO provided $16,000 for research in melanoma to Dr Judith S. Kaur, the first young investigator awarded with a YIA. Since then, ASCO has launched the careers of more than 700 fellows through its YIA program and has provided $30 million of research funding. The term of the YIA is 1 year, and the award currently provides $50,000 in research funding to award winners.

Other options for funding are available through the American Cancer Society (ACS), ASH, the Leukemia and Lymphoma Society, the Komen Foundation, and the Department of Defense (DOD), among other organizations.

When selecting an appropriate funding opportunity, you will want to consider your focus of research, prior research experience, level of institutional commitment, and citizenship status. Something to be aware of before you begin your application is that most of the grants are exclusive for US citizens, noncitizen nationals, or permanent residents. Except for K99/R00, most of the K awards from NIH are only available to US citizens or permanent residents.

For me, the best way to organize my projects is to have a deadline in my agenda. I suggest choosing a deadline to help keep you organized. It can be a deadline for a research workshop, abstract submission, or simply a date that you establish so that you have results before applying for jobs. This way, no matter how busy your fellowship is in terms of clinical responsibilities, you never lose sight of your goal.

Whether attending a scientific meeting for the learning experience or for presenting your own work, it is a great way to network with experts and meet fellows from other institutions. Getting to know fellows from other institutions has been one of the most valuable experiences during my training. It made me realize the strengths and weaknesses of my training, share experiences and available opportunities, and meet future colleagues with whom I will interact with for the rest of my professional life.

There are several reasons why you want to be involved with ASCO beyond grant opportunities. ASCO provides exceptional learning material available through ASCO University. Examples include the ASCO-SEP question bank (an essen- tial tool for boards preparation), tumor boards, diverse courses, flashcards oriented toward first-year fellows with basic oncology concepts, slides, and reviews of oncology literature.

You may also consider volunteering with ASCO and serving on a committee. No matter what your background, area of interest, or institution from which you come, we all can contribute. The best way to do so is by registering on the ASCO website (http://www.asco.org/about-asco/volunteerserve- committee).

You may also approach ASCO committee members and ASCO staff during meetings to express your interest. It may take time to get a chance to participate, but if you show interest, your opportunity will come. Similar opportunities are available through ASH and the American Association for Cancer Research (AACR).

There are other opportunities during the fellowship experience that can enrich your learning experience. These are diverse, depending on the areas of interest.

If you foresee a career in clinical research, something you may want to consider is applying for an external fellowship at the Cancer Therapy Evaluation Program (CTEP)/ NCI in the Investigational Drug Branch. This experience provides exposure to the review of incoming LOIs and protocols, and provides the opportunity to attend internal meetings between CTEP and pharmaceutical companies, or between CTEP and the FDA in regard to the development of new agents.

Another option is to apply for a rotation at the FDA. This opportunity will train you in federal regulations and the principles and practices of FDA medical product review, such as the design of clinical trials, monitoring of trials, identification of biomarkers, and clinical pharmacology.

If you are more focused on basic research, don’t miss some of the workshops AACR has available, such as the Annual AACR Aspen Workshop on molecular biology in clinical oncology.

	These Are the First Days of the Rest of Your Life

With all the available opportunities, it is important to confirm your initial decision that oncology is what you want to do for the rest of your life. Personally, I believe we are fortunate to have a very rewarding interaction with our patients and the privilege of sharing crucial moments in their lives. At the same time, we are part of a dynamic, evolving, ever changing and advancing field!

Filipa Lynce, MD, is a chief fellow in the hematology/oncology program at MedStar Georgetown University Hospital and MedStar Washington Hospital Center. 

Articles

Only by the end of my first year of fellowship did I realize that beyond your fellowship experience there is a lot you can gain.

Filipa Lynce, MD

Articles

Dr Lynce on Ongoing Trials Evaluating Novel Combinations in Inflammatory Breast Cancer

Dr Lynce on the Prognosis of Patients With Inflammatory Breast Cancer

Dr. Lynce on Remaining Questions With PARP Inhibitors in Breast Cancer

Dr. Lynce on FDA Approval of Atezolizumab/Nab-Paclitaxel in TNBC

How To Get the Most out of Your Fellowship