Factors associated with response to neoadjuvant chemotherapy and immune checkpoint inhibition in triple-negative breast cancer

• Published in: Journal of clinical oncology Vol. 41; no. 16_suppl; p. e12593
• Main Authors: LeVee, Alexis, Wong, Megan, Flores, Sarah, Ruel, Nora H., Lavasani, Sayeh Moazami, Patel, Niki, Sedrak, Mina S., Stewart, Daphne B., Waisman, James Ross, Yuan, Yuan, Mortimer, Joanne E.
• Format: Journal Article
• Language: English
• Published: 01.06.2023
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2023.41.16_suppl.e12593

e12593 Background: Immune checkpoint inhibition with pembrolizumab plus neoadjuvant chemotherapy is now the standard-of-care in patients with high-risk triple-negative breast cancer (TNBC) based on the KEYNOTE-522 trial. The trial demonstrated that the addition of pembrolizumab improves pCR, but it is currently unclear which patients benefit most from the addition of immunotherapy (IO). We sought to identify which demographic and clinical characteristics were associated with response to neoadjuvant pembrolizumab plus chemotherapy. Methods: We performed a single institution, retrospective study of early-stage TNBC patients treated with neoadjuvant chemotherapy and pembrolizumab between March 1 st , 2020 and December 1 st , 2022. We excluded patients who had not undergone definitive surgery. We collected demographic information, clinical and pathologic characteristics, and treatment data. Pathologic complete response (pCR) was defined by ypT0/Tis and ypN0. Multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by the City of Hope Institutional Review Board. Results: 67 patients were analyzed with a median age of 56 years and median BMI of 29. Self-reported racial groups included 25 Hispanic patients (37%), 23 non-Hispanic White (34%), 9 Asian (13%), 6 Black (9%), and 4 other/unknown (6%). 6 (9%) patients were BRCA1+ and 1 (1.5%) patient was BRCA2+. The majority of patients had invasive ductal carcinomas (91%), were clinical T2 stage (65.7%), and node negative (52.2%). The median number of cycles of neoadjuvant IO was 7 (IQR 4-8) and median months from start of IO to surgery was 6 (IQR 4.6-6.7). 42 (62.7%) patients had a pCR. Multivariate results showed that patients under 50 years at time of diagnosis (vs. age > 50 years), those with grade 3 (vs. 2), and those receiving 7 or more cycles of pembrolizumab (vs. < 7) had improved rates of pCR (ORs 5.7, 8.1, and 3.4, respectively, p < 0.05). BMI, race, BRCA1/2 status, histopathology, clinical T and N stage, and timing of start and end of IO to surgery were not significantly associated with pCR. Conclusions: Younger TNBC patients with high tumor grade were more likely to respond to treatment with neoadjuvant pembrolizumab and chemotherapy. More cycles of treatment with pembrolizumab was also associated with response. Further research to identify which patients with TNBC benefit from the addition of pembrolizumab to chemotherapy is necessary to determine whether its additional toxicity and cost are warranted.