Evaluating physician perspectives on neoadjuvant immunotherapy and chemotherapy in early-stage triple-negative breast cancer.

Abstract

e12633 Background: The Keynote-522 trial established neoadjuvant chemo-immunotherapy as a new standard of care for patients with early-stage triple negative breast cancer (TNBC). However, questions remain regarding the optimal chemotherapy backbone, duration of immunotherapy and the potential for chronic toxicities in this curative population. This study aimed to identify Canadian practices for the management of early-stage TNBC, areas of clinical uncertainty and interest in future clinical trials. Methods: A voluntary electronic survey was distributed to Canadian medical oncologists via an email database compiled by the Ottawa Hospital Research Institute, REthinking Clinical Trials (REaCT) program. The survey focused on prescribing practices prior to and following the Keynote-522 trial and the incorporation of immunotherapy into the neoadjuvant treatment of early-stage TNBC. The analysis is reported descriptively. Results: Out of the 50 oncologists from across Canada who responded to the survey, 36 were eligible to complete the survey in its entirety. Among respondents, 83.3% adopted the Keynote-522 chemotherapy backbone as their first choice for early-stage TNBC. However, only 47% reported following the trial protocol exactly. Common modifications included utilizing dose-dense (every 2-week) administration of anthracycline and cyclophosphamide (AC) (50%) with 6-week pembrolizumab dosing intervals (50%). Concerns regarding toxicity (39%) and schedule impracticality (25%) were primary drivers for protocol divergence. While 86% of physicians prescribe immunotherapy for eligible stage II/III TNBC, 50% would also offer it for Stage I (T1N0) disease. Areas of clinical uncertainty were highlighted as the management of stage I disease and the tolerability of the Keynote-522 protocol in the elderly and comorbid patients. Optimal adjuvant treatment practices also remain uncertain, particularly in the setting of patients with pathological complete response (pCR), with 39% of respondents indicating they felt there was currently insufficient data to support the continuation of pembrolizumab in the adjuvant setting. Finally, 100% of respondents indicated a need for more response-adapted regimens to mitigate treatment-related toxicities. Conclusions: Canadian oncologists have rapidly adopted neoadjuvant immunotherapy for early-stage TNBC as standard of practice but frequently modify the chemotherapy backbone to improve tolerability and clinical efficiency. Significant uncertainty persists regarding the treatment of stage I disease and elderly or comorbid patients, in addition to optimal adjuvant treatment practices. While research is ongoing to address these issues, more is needed, particularly efforts to support response-adapted treatment approaches.