Abstract P3-06-10: Immune-related adverse events (irAEs) and pathological complete response (pCR) rates in patients receiving neoadjuvant chemotherapy (CHT) and pembrolizumab (PEM) for early triple-negative breast cancer (eTNBC)
Authors: Marhold Maximilian , Udovica Simon , Wimmer Kerstin , Bago-Horvath Zsuzsanna , Robinson Tim , Fitzal Florian , Strasser-Weippl Kathrin , Bartsch Rupert 
Published: March 2023

Abstract
Background and Significance: Recently, the addition of the immune checkpoint-inhibitor PEM to CHT was shown to increase pCR rates and invasive event-free survival in the Keynote-522 (KN522) trial. Several irAEs are known to occur during use of PEM in various cancer entities. In our multicenter analysis we aimed to identify real-world occurrence rates of irAES and pCR rates in women receiving PEM and CHT, analogously to KN522, for eTNBC treatment. Methods: All patients receiving CHT + PEM for eTNBC treatment at participating centers were followed prospectively and monitored for occurrence of irAEs and neoadjuvant treatment outcome as defined by pCR from October 2020 until data cut-off on September 15th 2022. Only patients who underwent surgery for their primary tumor before data cut-off were included. Results: A total number of 22 patients with available pCR outcomes were included. All patients were female. Median age was 51 years (range 25-72). Mean tumor size at baseline was 29mm (range 10-75). 41% (9/22) of patients exhibited nodal involvement according to baseline radiological findings. Median MIB-1/Ki67 expression at biopsy was 70%. Patients received a median of 8 (range 1-8) neoadjuvant cycles of PEM and exhibited a median duration of CHT of 24 weeks (range 4-24). Neoadjuvant PEM was discontinued in 32% (7/22) of patients. Discontinuation of neoadjuvant treatment before week 18 occurred in 22,7% (5/22) of patients. We report irAE rates of any kind and all grades of 50% (11/22) and of grade 3-4 in 9% of patients (2/22). Steroids were administered in 7/11 patients experiencing irAEs (64%). 8 irAEs occurred during the neoadjuvant treatment phase, 3 during postneoadjuvant treatment with PEM. No grade 5 toxicity was observed. irAEs observed were hypothyroidism (n=3, all grade 2), arthritis (n=3, all grade 2), myocarditis (n=2, one grade 3/one grade 4), and single cases of hepatitis (grade 2), nephritis (grade 3) and pneumonitis (grade 1). 18% (4/22) of patients underwent mastectomy and 36% (8/22) of patients underwent axillary dissection. Lastly, upon definitive surgery of the primary tumor, we observed pCR in 50% (11/22) of cases. Patients who completed &gt;18 weeks of neoadjuvant therapy exhibited a pCR rate of 59% (10/17), whilst patients who completed ≤18 weeks of neoadjuvant therapy reached pCR in 20% of cases (1/5). Conclusion: We report real-world prospective data about irAE as well as pCR rates during eTNBC treatment with PEM and CHT. irAEs occurred in similar rates as observed in KN522, although numerically higher for irAEs of all grades. The pCR rate within our cohort was numerically lower than reported for KN522, most probably due to a low pCR rate observed for 5 of 22 patients included in this analysis who completed ≤18 weeks of neoadjuvant treatment. Looking at our data, we hypothesize that clinical benefit from combination therapy of PEM and CHT depends on reaching an adequate duration of &gt;18 weeks of neoadjuvant treatment.
Citation Format: Maximilian Marhold, Simon Udovica, Kerstin Wimmer, Zsuzsanna Bago-Horvath, Tim Robinson, Florian Fitzal, Kathrin Strasser-Weippl, Rupert Bartsch. Immune-related adverse events (irAEs) and pathological complete response (pCR) rates in patients receiving neoadjuvant chemotherapy (CHT) and pembrolizumab (PEM) for early triple-negative breast cancer (eTNBC) [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 P3-06-10.