Abstract P1-17-09: Efficacy of limited dose modifications for palbociclib-related grade 3 neutropenia in hormone receptor positive metastatic breast cancer

Abstract

Abstract Background. Endocrine therapy plus CDK 4/6 inhibitors is the foremost treatment for hormone receptor (HR) positive metastatic breast cancers (mBC). Previously, we reported safety profiles of palbociclib use with grade 3 neutropenia in HR-positive mBC. Here, we investigated two cohorts’ patients who had received palbociclib with or without dose interruptions and/or reductions on afebrile grade 3 neutropenia in terms of efficacy outcomes. Patients and methods. The combined cohort of consecutive mBC patients who received palbociclib with letrozole in 1st line setting (in four major cancer centers in Republic of Korea) was reviewed. We classified patients into 4 groups: Group 1 (patients who maintained palbociclib dose on afebrile grade 3 neutropenia, representing limited dose modification scheme), Group 2 (patients who experienced any dose modification on afebrile grade 3 neutropenia, representing conventional dose modification scheme), Group 3 (patients without the event of afebrile grade 3 neutropenia), and Group 4 (patients who experienced only grade 4 neutropenia) within the first 5 cycles. The primary endpoint was PFS difference between Group 1 and Group 2, and secondary endpoints included PFS and overall survival difference in all groups, and safety profiles of each group. Results. A total of 434 eligible patients recruited from Jan 2017 to Sep 2020 were allocated into 4 groups; Group 1 (n=172, 40.1%), Group 2 (n=128, 29.5%), Group 3 (n=102, 23.5%), and Group 4 (n=30, 6.9%). The overall incidence of palbociclib dose reductions was 272 (62.7%) and dosing delay was 181 (42.2%) in all groups. The median time to first dose reduction for all eligible patients was 3 months (2-5 months) and the median time to second dose reduction was 9 months (2-30 months). At the 12th cycle of treatment, 70.5% (105/at-risk patients of 149) of Group 1 patients still remained on 125mg of palbociclib, whereas no patient was on 125mg dose level but 66.3% patients (65/at-risk patients of 98) were on 100mg in Group 2. At the median follow-up of 23.7 months (95% CI: 21.6-25.8), Group 1 patients showed significantly longer PFS than Group 2 patients (P-value = 0.036, 2-year PFS rate: 67.9% in Group 1 and 55.3% in Group 2). The OS between Group 1 and 2 was not significantly different. The favorable PFS trend of Group 1 over Group 2 was observed across all subgroups. The overall toxicity profiles were not significantly different between Group 1 and Group 2. Conclusion. Our study demonstrates that the clinical practice of limited dose modifications for palbociclib-related grade 3 neutropenia might have more therapeutic benefits than the conventional dose scheme without increasing toxicities. Permissive approach to afebrile grade 3 neutropenia and prospective clinical trials for this new dose scheme are warranted. Funding: This study was supported by a grant from Pfizer. Citation Format: Seul-Gi Kim, Min Hwan Kim, Sejung Park, Gun Min Kim, Jee Hung Kim, Jee Ye Kim, Hyung Seok Park, Seho Park, Byeong Woo Park, Seung Il Kim, Jung Hwan Ji, Joon Jeong, Kabsoo Shin, Jieun Lee, Hyung-Don Kim, Kyung Hae Jung, Joohyuk Sohn. Efficacy of limited dose modifications for palbociclib-related grade 3 neutropenia in hormone receptor positive metastatic breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-17-09.