Real-world efficacy and adverse events of neoadjuvant immunotherapy in patients with early-stage triple-negative breast cancer: A multi-center experience.

e23293 Background: Pembrolizumab (pembro) combined with neoadjuvant chemotherapy (NAC) consisting of carboplatin- paclitaxel and doxorubicin-cyclophosphamide is the current standard of care in early-stage triple negative breast cancer (TNBC) based on KEYNOTE 522, which demonstrated improvements in pathologic complete response (pCR) to 65% but associated with high incidence of immune related adverse events (irAEs). We investigated real-world clinical outcomes and toxicity of this regimen. Methods: We conducted a retrospective, multi-center observational study among TNBC patients (pts) treated with NAC and pembro at 4 academic institutions from July 2021-December 2023. Data on clinicodemographic variables, irAEs, and clinical outcomes were collected. Multivariable logistic regressions were used to evaluate the association between demographic/clinical characteristics and pathological response while controlling for confounders. Analyses were performed in R (v4.2.3) at a significance level of ≤ 0.05. Results: 145 pts were analyzed, all females, with median age 53.5 years (IQR 43.4-62.7), 66% White and 23.4 % Black, median body mass index 28.3 kg/m 2 (IQR 23-32), 55.6% stage II and 34% stage III disease. Median follow up was 12.3 months from the date of diagnosis. 94 pts (64.8%) attained pathological complete response (pCR). The median number of Pembro cycles prior to surgery was 7. Receipt of < 8 pembro cycles was associated with lower pCR rate compared to ≥ 8 cycles (37.2% vs 62.8%, p = 0.03). Pts in pCR group were younger than in non-pCR group (50.8 vs. 58.5 years, p = 0.002). The non-pCR group received lower relative dose intensity (RDI) of carboplatin (91.7% vs 96.6%, p = 0.001), paclitaxel (90% vs 92%, p = 0.03), cyclophosphamide (91% vs 96%, p = 0.04)compared to the pCR group. Median absolute eosinophil count (AEC) was higher in pCR group compared to non-pCR group (140/μl vs 110/μl). Higher baseline AEC was associated with higher pCR rate on multivariate analysis (OR 4.54, CI 2.08 - 50.0, p = 0.02) after adjusting for confounders such as age, number of pembro cycles, RDI, race and comorbidities. No other variables were predictive of pCR in multivariate analyses. 48.3% pts experienced irAE of any grade and 38% grade 3+ irAE. The most common irAEs were hypothyroidism (21.3%), transaminitis (20%), rash (17.5%), colitis (12.5%), adrenal insufficiency (10%), pneumonitis (8.8%), and infusion reactions (8.8%). No significant difference in pCR rate (57% vs 62%) and incidence of irAEs (42% vs 50%) were noted between Black and White pts respectively. Conclusions: The pCR rate in our study (64.8%) was comparable to KEYNOTE 522 but there was higher incidence of irAEs (48.3%). Higher AEC at baseline was associated with improved pathologic response to chemoimmunotherapy. More real world studies are needed to confirm the high incidence of irAEs that was observed in our study.