Jennifer K. Litton, MD, discusses challenges determining the optimal sequencing of PARP inhibitors in early-stage triple-negative breast cancer.

Dr Litton on Navigating the Sequencing of PARP Inhibitors in Early-Stage TNBC

Jennifer K. Litton, MD, MHCM, medical oncologist, Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses challenges in determining the optimal sequencing of PARP inhibitors in patients with early-stage triple-negative breast cancer (TNBC) and provides examples of factors she considers when making this decision in clinical practice.

FDA approval of olaparib (Lynparza) for patients with high-risk, early-stage breast cancer

 mutation and have previously received chemotherapy either before or after surgery represents a significant advancement in treatment options, Litton begins. The approval was based on findings from the phase 3 OlympiA trial (NCT02032823), in which olaparib significantly improved invasive disease-free survival vs placebo. Accordingly, olaparib is now an adjuvant standard of care for patients with TNBC or hormone receptor (HR)–positive disease and a germline 

 mutation, particularly those with residual disease, Litton states.

However, the treatment paradigm for adjuvant therapy for high-risk breast cancer is rapidly evolving, with several highly effective drugs from different trials converging in this field, Litton notes. Currently, there is also a lack of data on the optimal sequencing of these agents, presenting a challenge in clinical decision-making, she adds. In light of this, the selection of PARP inhibitors in early disease stages is often up to an investigator's discretion and experience, Litton explains.

Litton states that in her own practice, continuing a PARP inhibitor plus immunotherapy in the adjuvant setting should be considered for patients with a germline 

 mutation who had previously received immunotherapy, given the available safety data and potentially favorable outcomes with these agents compared with alternative treatments such as capecitabine (Xeloda).

For patients with HR-positive breast cancer, despite the approval of agents such as abemaciclib (Verzenio) and the anticipated approval of ribociclib (Kisqali) in this setting, a PARP inhibitor may still be preferred initially, Litton continues. However, there is a lack of data on using CDK4/6 inhibitors post–PARP inhibitor therapy. Individualized discussions with patients are essential to weigh the benefits and risks of each treatment option until more data become available to guide sequential therapy decisions, Litton concludes.

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Jennifer Keating Litton, MD, faculty, The University of Texas Graduate School of Biomedical Sciences, vice president, Clinical Research, Department of Chief Scientific Office, The University of Texas MD Anderson Cancer Center, discusses research areas of interest in 

-mutated, endocrine receptor–positive, HER2-negative breast cancer.

 mutations have been found to potentially increase resistance to aromatase inhibitors, additional data is needed to determine the best treatment path for a patient with an 

mutation who is responding to an aromatase inhibitor, Litton says. If a patient is found to have an 

 mutation but is responding to an aromatase inhibitor, a change to another therapy is not warranted, based on currently available data, Litton adds.

However, ongoing studies are evaluating if patients harboring an 

 mutations can benefit more from switching to another therapy, such as fulvestrant (Faslodex) or another selective estrogen receptor degrader, Litton says. Additionally, the presence of circulating tumor cells could also play a larger role in determining treatment as agents continue to evolve, Litton concludes.

Jennifer Keating Litton, MD, discusses research areas of interest in ESR1-mutated, endocrine receptor–positive, HER2-negative breast cancer.


Dr. Litton on Remaining Questions in ESR1-Mutated Breast Cancer

Jennifer Litton, MD, faculty, University of Texas Graduate School of Biomedical Sciences, and vice president of clinical research, Department of Chief Scientific Office, The University of Texas MD Anderson Cancer Center, discusses the safety of talazoparib (Talzenna) in the neoadjuvant treatment of patients with germline 

-positive, early-stage HER2-negative breast cancer.

A phase 2 study (NCT03499353) evaluated the efficacy of neoadjuvant talazoparib in this patient population and showed that the toxicities observed with the agent in the early-stage setting were similar to those reported with the agent in the metastatic setting, according to Litton. The key difference was that a slightly higher rate of grade 1 or 2 alopecia was reported in the phase 3 EMBRACA trial (NCT01945775), Litton says. These results suggest that talazoparib has efficacy as a single agent in patients with a germline 

 mutation who have previously received treatment with an anthracycline or taxane and experience a recurrence, it is not ideal to give these chemotherapies again, according to Litton, who adds that other therapeutic options to avoid adverse effects like cardiotoxicity are needed. To this end, talazoparib is a potential option that should be further studied as a treatment option for this population, Litton concludes.

Jennifer Litton, MD, discusses the safety of talazoparib (Talzenna) in the neoadjuvant treatment of patients with germline BRCA1/2-positive, early-stage HER2-negative breast cancer. 

Dr. Litton on the Safety of Neoadjuvant Talazoparib in HER2-Negative Breast Cancer

Jennifer K. Litton, MD, associate professor in the Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the phase 3 EMBRACA trial in patients with germline 

-mutated metastatic HER2-negative breast cancer. 

The EMBRACA trial is the largest trial of PARP monotherapy to date, says Litton. In this international study, patients were randomized 2:1 to receive either talazoparib (Talzenna) once daily or ​physician's choice chemotherapy.

Initial findings from the study showed a 3-month progression-free survival improvement with talazoparib compared with chemotherapy, says Litton.

Updated findings presented at the 2020 AACR Virtual Annual Meeting revealed that the PARP inhibitor did not demonstrate a statistically significant overall survival benefit versus chemotherapy in this patient population.

Jennifer K. Litton, MD, discusses the phase 3 EMBRACA trial in patients with germline BRCA1/2-mutated metastatic HER2-negative breast cancer. 

Dr. Litton on the EMBRACA Trial in Advanced BRCA1/2+ Breast Cancer 

Jennifer K. Litton, MD, associate professor in the Department of Breast Medical Oncology, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, discusses the potential advantage of using biosimilars in oncology.

Litton says she is an advocate of anything that could reduce the cost of cancer care, as financial toxicity is a real issue for many patients. Co-payments can vary, she adds. Although some payments are manageable, others have families questioning whether they have enough savings to afford treatment.

There is not going to be one single fix that will reduce the cost of cancer care, says Litton. The problem will need to be addressed on several fronts. Biosimilars could be an integral component in decreasing the cost of therapy, but it won’t be the only one.

On September 14, 2017, the FDA approved bevacizumab-awwb (Mvasi) a biosimilar for bevacizumab (Avastin), marking the first biosimilar to receive regulatory approval in the United States for the treatment of patients with cancer. Since then, several biosimilars have garnered approvals for biologic agents such as trastuzumab (Herceptin) and rituximab (Rituxan).

Jennifer K. Litton, MD

Articles

Dr Litton on Navigating the Sequencing of PARP Inhibitors in Early-Stage TNBC

Dr. Litton on Remaining Questions in ESR1-Mutated Breast Cancer

Dr. Litton on the Safety of Neoadjuvant Talazoparib in HER2-Negative Breast Cancer

Dr. Litton on the EMBRACA Trial in Advanced BRCA1/2+ Breast Cancer

Dr. Litton Discusses the Potential Advantage of Using Biosimilars in Oncology