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Neoadjuvant talazoparib induces pathologic complete response in BRCA-mutated operable breast cancer
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Neoadjuvant talazoparib without chemotherapy induced a high rate of pathologic complete response among women with operable breast cancer who harbored germline BRCA mutations, according to results of a small single-arm pilot study published in Journal of Clinical Oncology.
The poly(ADP-ribose) polymerase (PARP) inhibitor also exhibited a manageable toxicity profile, researchers wrote.
“This is the first study looking at a targeted therapy alone in this setting without chemotherapy, so the proof of principle that this can and/or should be done for patients is, in my opinion, what is being investigated,” Jennifer K. Litton, MD, associate professor of breast oncology at The University of Texas MD Anderson Cancer Center, told HemOnc Today. “It will not yet address if patients can definitively forgo chemotherapy.”
In the pilot study — designed to acquire data to power a larger trial — Litton and colleagues evaluated pathologic response to single-agent talazoparib (Talzenna, Pfizer) among 20 women (median age, 38 years; range, 23-58) with operable breast cancer and germline BRCA mutations (BRCA1, n = 16; BRCA2, n = 4).
Fifteen of the women had triple-negative breast cancer and five had hormone receptor-positive disease. Most of the women (n = 12) had stage II disease and five had stage I disease. Three women had stage III disease, including one with inflammatory breast carcinoma and one with metaplastic chondrosarcomatous carcinoma.
Women received 1 mg daily talazoparib for 6 months without chemotherapy, followed by definitive surgery and adjuvant treatment at the discretion of the physician.
Researchers measured pathologic response using a residual cancer burden (RCB) calculator, with responses ranging from RCB-0 (pathologic complete response) to RCB-III.
Results showed an RCB-0 rate of 53% (95% CI, 32-73) and RCB-0/I rate of 63% (95% CI, 41-81). Two patients had RCB-I, five had RCB-II responses and three had RCB-III responses. One woman with a lymph node enlarging after 5 months of therapy proceeded to chemotherapy before surgery and was not included in the RCB analysis.
Researchers observed RCB-0 or RCB-I responses among most women with BRCA1 mutations (53%; 95% CI, 27-79) and all women with BRCA2 mutations (100%; 95% CI, 40-100), as well as among women with hormone receptor-positive and triple-negative breast cancer.
Eleven women completed therapy at the full 1 mg dose. Hematologic toxicity led to dose reductions to 0.75 mg for two women, 0.5 mg for six women and 0.25 mg for one woman.
Eight women experienced grade 3 anemia that required a transfusion, three experienced grade 3 neutropenia, and one woman had grade 4 thrombocytopenia.
Grade 1 or grade 2 toxicities included nausea, fatigue, neutropenia, alopecia, dizziness and dyspnea.
“For patients with hormone receptor-positive breast cancer, they may feel more confident going to an endocrine therapy adjuvantly and forgoing chemotherapy,” Litton said. “It may also be very useful for those patients who have had multiple cancers and previous chemotherapy exposures. Quality of life and fertility measures are being followed in the larger confirmatory study and will be important to report.” – by John DeRosier
Disclosures: Litton reports consultant/advisory roles with and/or institutional research funding from AstraZeneca, Bristol-Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Jounce Therapeutics, Medivation/Pfizer and Novartis; a speakers bureau role with and patents or royalties from UpToDate; and a speakers bureau role with and travel expenses from Med Learning Group, Medscape and Physicians’ Education Resource. Please see the study for all other authors’ relevant financial disclosures.
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