The effect of switching from ribociclib to palbociclib due to toxicity in hormone receptor–positive, HER-2–negative metastatic breast cancer: A real-world, multicenter, retrospective study.

Abstract

e24144 Background: In metastatic hormone receptor (HR)-positive and HER-2-negative breast cancer, toxicity with CDK 4/6 inhibitors is seen at a rate that cannot be underestimated. We aimed to investigate the clinical effect of switching from ribociclib to palbociclib in patients who developed toxicity, whether there was a difference in progression-free survival (PFS), and whether toxicity persisted or new side effects developed after the switch. Methods: This retrospective and observational study includes participants from nine centers who were followed between September 2020 and September 2025. 1,392 patients were screened. Toxicity causes, drug-drug interactions (DDI), objective response rates (ORR), and PFS were examined. All statistical analyses were performed using IBM SPSS Statistics 25.0. Results: 44 patients were included in the study. All patients were female, with a median age of 57 (50,25-67,5). De novo metastatic disease was present in 30 (68,2%) patients, and 33 (75%) patients were postmenopausal. There were 34 (77.3%) patients treated with ribociclib in the first line treatment. The most common cause of switching was hepatotoxicity, accounting for 18 cases (40,9%). Cardiotoxicity was observed in 11 patients (25%), skin toxicity in 9 patients (20.5%), refractory grade 3 neutropenia in 2 patients (4.5%), nephrotoxicity in 3 patients (6.8%), and grade 3 anemia in 1 patient (2.2%).The median time to switching was 4.3 months. There was no statistically significant difference between DDI and switch time, p=0.118. The ORR in 31 patients was 70.9%, as the follow-up period was too short to evaluate response in 13 patients before toxicity. In 3 patients who switched from ribocicllib to palbociclib after toxicity, the response could not be evaluated due to the short duration of treatment. The ORR in 41 patients was 73.1%. The median (m) follow-up period was 23.9 months. The OS was not yet mature, as 11 patients (25%) had died. The mPFS in all patients was 29.9 (24.4-35.5) months. The PFS rate at month 24 was 65.3%. In patients with a switch in <4.3 months (n:22), mPFS was 31.4 (24.1-38.8) months, while in patients with a switch in ≥ 4.3 months (n:22), mPFS was 28.4 (22.2-34.6) months, p=0.682 . When patients treated with ribociclib in the first line were evaluated, mPFS was 31.6 (23.6-39.6) months in those with a switch <4.3 months (n:18), while in those with a switch ≥ 4.3 months (n:16) mPFS was 25.5 (20.1-31) months, p=0.618. Multivariate Cox regression analysis revealed that the timing of the switch did not affect the prognosis. Conclusions: In metastatic HR-positive and HER-2-negative breast cancer, when toxicity develops with ribociclib, switching to palbociclib should be considered instead of reducing the dose or discontinuing treatment, and it should be remembered that the toxicity will not continue.