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Background Pembrolizumab (pembro, anti-PD-1 antibody) combined to chemotherapy (CT) in neoadjuvant/adjuvant setting has demonstrated its efficacy for early triple negative breast cancer (eTNBC). Pembro obtained FDA marketing authorization on July 26, 2021 and is available in France through the French Early Access Program. Methods We built an ambispective cohort that aimed to evaluate the efficacy and safety of the pembro-CT combination in the real world setting in patients with eTNBC. This study included patients treated from September 2021 to May 2022, at Institut Curie, France. Patients provided written authorization to report their clinical data. We report here the safety results. Results Between September 2021 and May 2022, 51 patients were included. Median age was 49 years [29; 68]. Germline mutations were recorded in 8 patients (22.2% of 36 tested patients). All pts were ECOG PS 0 or 1. Baseline clinical TNM stage were T1 (8 pts, 15.7%), T2 (30 pts, 58.9%), T3 (7 pts, 13.7%) and T4 (6 pts, 11.7%). Out of 37 pts (72.5%) with radiological axillary lymph node involvement, 19 pts (51.4%) had positive node involvement confirmed by guided fine needle aspiration. SBR grade 2 and 3 were observed in 9 (17.6%) and 42 (82.4%) pts, respectively. HER2 score was 0 or 1+/2+(FISH neg) for 31 (60.8 %) and 20 pts (39.2 %), respectively. A CPS score ≥ 10 was observed in 19 pts (50% of 38 tested patients). The CT backbone was a combination of carboplatin (Cb) plus weekly paclitaxel (wP) 4 courses (with Cb regimen AUC 5 q3W (81.1%), AUC4 q3w (5.4%) and AUC1,5 q1w (13.5%), and wP 80 mg/m²), followed by standard AC60/600 q3w for 4 courses. Out of the 37 pts (72.5%) who completed the Cb + wP 4 courses, all experienced adverse events (AEs), including 21 pts (56.8%) with at least 1 grade ≥ 3 AE (anemia 5.4%, thrombopenia 5.4%, neutropenia 51.5%, neuropathy 2.7%). Transfusion support was needed for 8 pts (21.6%). Grade ≥ 2 neuropathy occurred in 3 pts (8.1 %). Dose reduction and drug discontinuation were performed in 9 (24.3%) and 5 pts (13.5%), respectively. On the entire cohort, 15 pts (29.4%) had IrAE all grades: dysthyroidism (6 pts, 11.7%), skin toxicity (2 pts, 3.9%), adrenal insufficiency (1 pt, 2%), hypophysitis (1 pt, 2%), immune-allergic nephropathy (1 pt, 2%), suspicion of myocarditis (1 pt, 2%), hepatitis (1 pt, 2%) and ophthalmologic AE (1 pt, 2%). Consequently, after a median follow up of 5 months, pembro postponement and permanent discontinuation were performed in 7 (13,7%) and 5 pts (9,8%), respectively. At abstract submission 6 pts had breast surgery (pCR in 5 pts = 83.3%). Conclusions Our real-world data are consistent with the results of the KEYNOTE-522 trial in terms of patients characteristics. We observed a very high rate of hematological and immune related adverse events, frequently leading to dose reduction or discontinuation, underlying the need for a very close clinical management of those patients. Updated data including toxicity during the whole neoadjuvant sequence and pCR rate will be presented at the meeting. Citation Format: Delphine Loirat, Emilie ARNAUD, Khaoula ALAOUI, Pauline VAFLARD, Sinen KORBI, Dalila MEZIANI, Lucie THIBAULT, Romain-Pacome DESMARIS, Jean-Guillaume FERON, Jean-Yves Pierga, Francois-Clement Bidard, Paul COTTU. Real-world toxicity of pembrolizumab-based neoadjuvant regimen in patients with early triple negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-06-09. |
