Abstract P2-12-12: Impact of the addition of pembrolizumab to neoadjuvant chemotherapy in triple negative breast cancer in Ireland: a retrospective, multi-centre, real-world study

Abstract Background: The 60-month follow up data from the phase III KEYNOTE 522 (KN522) trial reported that the addition of pembrolizumab (pembro) to chemotherapy improved event free survival (EFS) and increased the rate of pathological complete response (pCR).1 As a result, the KN522 regimen is standard of care for stage II/III TNBC. The KN522 trial reported that immune-mediated adverse events (IRAEs) ≥ grade 3 occurred in 12.9% of pts in the pembro arm and 1.0% of pts in the chemo only arm.2 Methods: We conducted a retrospective observational cohort study of patients (pts) with TNBC, stage II-III, who received paclitaxel and carboplatin followed by doxorubicin plus cyclophosphamide, associated with pembro, as per the KN522 trial, between January 2023 and May 2024 at five Irish institutions. We examined the real-world pCR rate and IRAEs. Results: 67 patients (pts) started the KN522 regimen. The median age was 49 years (range 32-77). 47 pts (70%) had T1-2 tumours, 19 pts (28%) had T3-4 tumours, data was unavailable for 1 pt. 38 pts (57%) had node positive disease. 16 pts (23%) experienced an IRAE of ≥ grade 3 during treatment. 13 pts (19%) experienced an IRAE ≥ grade 3 in the neoadjuvant phase and 3 pts (4%) experienced an IRAE ≥ grade 3 in the adjuvant phase. The most common ≥ grade 3 IRAEs observed were hepatitis (n=6, 9%); nephritis (n=4, 6%) and colitis (n=3, 4%). 34 pts (51%) were hospitalized at least once during treatment. 13 pts were hospitalized on more than once occasion, and a total of 54 hospitalisations were recorded for the group during treatment. To date, 3 pts have been hospitalised during the adjuvant phase. Of the 40 pts who had undergone surgery at the time of data analysis, 26 pts (65%) had a pCR. Among those pts who experienced a pCR, a higher proportion had stage II disease (n=20, 77%) compared with the pts who did not experience a pCR (n=9, 64%), although this was not statistically significant (p=0.469). There was a lower instance of ≥ grade 3 IRAEs observed among pts who experienced a pCR (n=4, 15%) compared with those who did not experience a pCR (n=5, 36%), however this was not statistically significant (p=.234). A lower number of patients who experienced a pCR were hospitalised during the neoadjuvant phase of treatment (n=12, 46%) compared with pts who did not experience a pCR (n=8, 57%). The median number of cycles of pembro received among patients who experienced a pCR was 8 (range 1-10), compared with a median of 7 cycles among patients who did not experience a pCR (range 2-10). Conclusion: We found a high pCR rate among pts who completed the neoadjuvant phase of treatment. The IRAEs observed were in line with the known side effects of the agents. IRAEs ≥ grade 3 were higher in our real-world cohort compared with KN522 published data.2 Higher rates of IRAEs ≥ grade 3 have been reported among other real-world cohorts.3 We found a high rate of hospitalization in our cohort, which is also in line with published real-world data.4 The hospitalization rates observed with this regimen are higher than hospitalisation rates with neoadjuvant chemotherapy alone, which range from 6.2%-10% for pts aged <65 years and 12.7%-24% for pts ≥65 years.5 In this cohort, pts who experienced a pCR had a higher frequency of stage II disease and lower rates of ≥grade 3 IRAEs compared with those who did not experience a pCR, although this did not reach statistical significance. This real-world study supports trends observed in other similar studies and highlights the complexity of managing the toxicities arising from the addition of immunotherapy to standard neoadjuvant chemotherapy. Citation Format: Karine Ronan, Laurann Rabbitt, Karolina Weiner-Gorzel, Benjamin Mathewson, Lisa Prior, Jennifer Westrup, Janice Walshe, Michaela Higgins, Hannah O Connor, Beth Costello, Shahid Iqbal, Catherine Kelly, Maccon Keane, Sonya Chew, Emily Harrold. Impact of the addition of pembrolizumab to neoadjuvant chemotherapy in triple negative breast cancer in Ireland: a retrospective, multi-centre, real-world study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-12.