NEOTALA’s invited discussant, Lisa Carey, MD, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research and Deputy Director of Clinical Sciences at the University of North Carolina-Chapel Hill, saw the findings as part of a bigger trend toward reducing the use of chemotherapy.
Lisa Carey, MD
As she noted, NEOTALA included patients with triple-negative breast cancer, all with germline BRCA1/2 mutations, who received single-agent talazoparib for 24 weeks preoperatively and, in the adjuvant setting, could receive treatment by investigator’s choice. In the intention-to-treat and evaluable populations, the pathologic complete response rate was approximately 45% to 50%.
“With that kind of pathologic complete response rate from a single-agent PARP inhibitor, this is clearly very active in these germline carriers and is close to what we would expect with polychemotherapy,” Dr. Carey said. She noted, however, that 16% of patients experienced disease progression on therapy, “which is considerably higher than one would expect.”
This leads to some questions: Would early evaluation of response to talazoparib help clinicians tailor treatment? Is it important to identify the 16% or so of patients who will experience disease progression on this regimen? Would elimination of those patients have further augmented the responsiveness to this single-agent treatment?
“Also at ASCO, we heard a plenary presentation showing compelling improvement in disease-free survival with an adjuvant PARP inhibitor [olaparib] after chemotherapy in the OlympiA trial,”1 she said, “so we all have to ask ourselves, ‘Is this an opportunity to reduce the use of chemotherapy in this disease?’ I would argue that it is.”
Less chemotherapy may become feasible “by leveraging the importance and activity of these drugs,” she explained. “We are increasingly leveraging drug response for decision-making; in residual disease, we are adding adjuvant drugs in HER2-positive and triple-negative breast cancer. There are ongoing trials that are omitting drugs after pathologic complete response. There are predictive biomarkers for targeted drugs that may include early drug response as well as baseline biology,” Dr. Carey said, though she cautioned that these findings need “careful validation” since early response evaluation requires on-therapy biopsy.
DISCLOSURE: Dr. Carey has received institutional research funding from AbbVie, NanoString Technologies, Novartis, Seattle Genetics, Syndax, and Veracyte; has an immediate family member who holds intellectual property in Falcon Therapeutics; has held uncompensated relationships with Eisai; and has held uncompensated institutional relationships with Aptitude Health, AstraZeneca/Daiichi Sankyo, Exact Sciences, G1 Therapeutics, Genentech/Roche, GSK, Novartis, and Sanofi-Aventis.
REFERENCE
1. Tutt A, Garber JE, Kaufman B, et al: OlympiA: A phase III, multicenter, randomized, placebo-controlled trial of adjuvant olaparib after (neo)adjuvant chemotherapy in patients with germline BRCA1/2 mutations and high-risk HER2-negative early breast cancer. 2021 ASCO Annual Meeting. Abstract LBA1. Presented June 6, 2021.
