Abstract PO3-03-12: Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer
Authors: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer
Journal: Cancer Research (2024)

Abstract Background: The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) became a standard-of-care for the treatment of early-stage triple negative breast cancer (TNBC) after the phase III KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates and event free survival with the combination. To date, clinical predictors of response to pembro with NAC are lacking. We sought to identify real-world clinical characteristics and treatment variables associated with response to NAC with pembro. Methods: We performed a single institution, retrospective study of early-stage TNBC patients diagnosed between February 1st, 2020 and December 1st, 2022 who were treated with NAC and pembro. Patients who had not undergone definitive surgery were excluded. Demographic information, clinical and pathologic characteristics, and treatment data were collected. pCR was defined as ypT0/Tis and ypN0. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. This study was approved by an Institutional Review Board. Results: Of the 94 patients analyzed, 93 were female and 1 was male. The median age was 55 years (IQR 47 – 61.8) and median body mass index (BMI) was 30 (24.1-33.6). Self-reported racial/ethnic groups included 37 non-Hispanic White (39.4%), 33 Hispanic (35.1%), 13 Asian (13.8%), 7 Black (7.4%), and 4 other/unknown (4.3%). 8 (8.5%) and 2 (2.1%) of patients had deleterious germline BRCA1+ and BRCA2+ mutations, respectively. The majority of patients had invasive ductal histology (90.4%), clinical T2 stage (68.1%), and node negative (55.3%) disease. 61 (64.9%) patients completed the planned 8 cycles of NAC, while 42 (44.7%) completed the planned 8 cycles of neoadjuvant pembro. A pCR (ypT0/Tis ypN0) was achieved in 60 (63.8%) of the 94 patients. Among those who achieved a pCR, 32 (53.3%) completed the prescribed course of NAC and pembro in combination, whereas 9 (47.1%) of the 34 patients with residual disease did not. In univariate analyses, patients under 55 years at time of diagnosis (vs. age &amp;gt;55 years), higher ki-67, those completing the prescribed course of NAC, those completing the prescribed course of pembro, the months from start of NAC to surgery, and the months from start of pembro to surgery were associated with pCR. The duration from start of NAC or pembro to surgery overlapped considerably with the response explained by completion of NAC or pembro, respectively. Although pCR estimates were lower for Hispanic (60.6%) and non-Hispanic White patients (Black: 57.1%, Asian: 53.8%, and Other: 50%) when compared to non-Hispanic White patients (73.0%), the results were not statistically significant. In multivariate analyses, patients under 55 years at time of diagnosis (OR 3.06, 95% CI:1.18-8.0, p=0.02) and those completing the full course of pembro (OR 2.86, 95%CI: 1.08-7.58, p=0.034) had improved rates of pCR. BMI, race, BRCA1/2 status, histology, clinical T and N stage, grade, time between start/end of NAC and IO to surgery were not significantly associated with pCR on multivariate analysis. Conclusion: In our experience, younger TNBC patients were more likely to achieve a pCR with NAC with pembro. Moreover, the completion of the planned course of pembro prior to surgery was also associated with improved pCR rates. These findings suggest that adherence to neoadjuvant pembro prior to surgery may be more important than the completion of the NAC. Further research to identify the optimal exposure of NAC with pembro is needed to refine treatment recommendations in this high-risk population. Citation Format: Alexis LeVee, Megan Wong, Sarah Flores, Nora Ruel, Heather McArthur, James Waisman, Joanne Mortimer. Factors associated with response to neoadjuvant chemoimmunotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-03-12.