Abstract P5-11-10: Abemaciclib following Palbociclib in metastatic breast cancer (MBC): Characteristics of patients (pts) with durable response
Authors: Veronica Mariotti, Hung Khong, Hatem Soliman, Ricardo Costa, Hyo Han
Journal: Cancer Research (2020)

Abstract Background There is limited data on efficacy of Abemaciclib following other CDK4/6 inhibitors (CD4/6is) use in metastatic breast cancer (MBC), and on the factors that might determine a durable response. The aim of this study was to analyze the efficacy of Abemaciclib-based therapy (ABT) after exposure to Palbociclib in Estrogen Receptor positive MBC patients (pts), and to examine the demographics and tumor characteristics of pts with durable response. Methods We queried our EMR database for pts who received Abemaciclib from 9/2017 - 5/2019 after prior exposure to Palbociclib. Only pts who progressed on Palbociclib were included. Under IRB approved protocol we retrospectively collected demographics, tumor characteristics, disease status, tumor genomic mutations, toxicities and survival of the pts. We identified the pts who had a durable response to ABT, defined as progression-free survival (PFS) over 6 months, and analyzed the differences between these groups. We used linear regression, t-test, Kaplan Meier survival curves and Chi-square for statistical analysis. Results 22 female pts (median age 55.2 years, range 39-76) were identified. Of all pts, 16 (72.7%) had visceral involvement, and 6 (27.3%) had brain metastasis. The pts received a median of 5.6 prior therapy lines (range 1-13), including endocrine-based (median 3.0, range 1-6), and non-endocrine based (median 2.0, range 0-10) therapies. Palbociclib was given in combination with Fulvestrant in 7 (31.8%) pts, with Letrozole in 13 (59.1%) pts and in combination with AI and Fulvestrant in 2 (9%) pts. The median PFS on Palbociclib-based therapy (PBT) was 9 months (95% CI 0.0-6.7). Abemaciclib was given alone in 3 (13.6%) pts, in combination with AI in 8 (26.6%) pts, with Tamoxifen in 3 (13.6%) pts, with Fulvestrant in 7 (31.8%) pts, and with both Tamoxifen and Fulvestrant in 1 (4.5%) pts. The median PFS on ABT was 3 months (95% CI 3.2-14.7). Abemaciclib was dose reduced in 7 (31.8%) pts due to gastrointestinal toxicities. We divided our population in 2 groups based on PFS on ABT (superior or inferior to 6 months). Five (22.7%) pts had durable response to ABT. Of those pts 2 (33.3%) had a longer PFS compared to prior PBT PFS (table). There was no statistically significant difference between the 2 groups in terms of age, duration of PBT, number of therapy lines received prior to ABT, presence of visceral or brain metastatic disease. 13 (59.1%) pts had tumor genomic analysis by FoundationOne (6, from metastatic tissue) or Guardant360 (7, from peripheral blood). It has recently been shown that RB1 and PIK3CA mutations are associated with exposure to CD4/6i and that ESR1 alteration might be associated with worse PFS in pts treated with CDK4/6i (Razavi P, 2019; Bardia A, 2019). In our pts RB1 was not mutated, ESR1 was mutated in 5 (38.4%) pts (one with durable response), and PIK3CA in 7 (53.8%) pts (one with durable response). Conclusions ABT can result in durable response in selected pts who progressed on prior Palbociclib. Prospective studies are warranted to establish which factors might contribute to the success of a specific sequence of therapies with CDK4/6is. Pts with durable response. Let = Letrozole, Ful = Fulvestrant, Ana = Anastrozole, Tam = TamoxifenSubjectNumber of prior linesAge (years)SequentialPalbociclib therapyPalbociclib PFS (months)Abemaciclib therapyAbemaciclib PFS (months)Brain metastasesVisceral metastasesAbemaciclib dose reductionGene Mutations1554NoLet12.6Ful7.4NoYesNoEGFR, APC2449YesFul4.1Ful9.4YesYesYes3676YesLet16.7Ana9.5NoNoNo4961YesFul19.9Ful, Tam13.2NoYesYesESR1, PIK3CA, ATM, NTRK1, EGFR, MET5352NoLet7.5Tam16.5NoYesYesSMAD4 Citation Format: Veronica Mariotti, Hung Khong, Hatem Soliman, Ricardo Costa, Hyo Han. Abemaciclib following Palbociclib in metastatic breast cancer (MBC): Characteristics of patients (pts) with durable response [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-10.