Abstract P4-22-06: Treatment postprogression in women with endocrine-resistant HR+/HER2- advanced breast cancer who received palbociclib plus fulvestrant in PALOMA-3
Authors: Turner NC , André F , Cristofanilli M , Verma S , Iwata H , Loi S , Harbeck N , Ro J , Colleoni M , Zhang K , Huang Bartlett C , Giorgetti C , Slamon D 
Published: March 2017

Abstract
Background: Palbociclib (PAL) plus fulvestrant (FUL) demonstrated significant improvement in progression-free survival (PFS) vs placebo (PBO) plus FUL in women with HR+/HER2- advanced breast cancer (ABC) whose disease had progressed on prior endocrine therapy (ET). Because the effectiveness of standard therapies after progression on PAL is unknown, it is important to understand whether the benefits of PAL with respect to PFS extend to subsequent treatments.
Method: Pre-, peri-, and postmenopausal patients (pts) with HR+/HER2- ABC who had relapsed/progressed on prior ET were randomized 2:1 to PAL (125 mg/d oral [3 wk on drug, 1 wk off]) + FUL (500 mg/mo intramuscular, per standard of care) or PBO+FUL. One prior line of chemotherapy (CT) for ABC was allowed. For 9 mo immediately after participation in PALOMA-3, pts were assessed every 3 mo for information on poststudy progression and treatment; the type of treatment, its duration, and sites of progression were analyzed.
Results: As of Oct 2015, with a median follow-up of 15.8 mo for PAL+FUL and 15.3 mo for PBO+FUL, 333 PFS events were observed (200 and 133, respectively). Median PFS was 11.2 vs 4.6 mo (hazard ratio [HR], 0.497 [95% CI, 0.398–0.620]; P&lt;0.0001). In both treatment arms, the most common sites of disease progression were the liver (149 [43%] and 94 [54%]) and bone (55 [16%] and 43 [25%]). 1 pt in each treatment arm developed new brain metastasis. The most commonly used postprogression regimens were capecitabine (n=57 [28.8%]), paclitaxel (n=22 [11.1%]), and exemestane (n=34 [17.2%]). Median time to subsequent CT (from randomization to the start of the first CT treatment poststudy) was longer with PAL+FUL (252 d) than with PBO+FUL (132 d). This was also observed in pts with visceral disease who never received CT in the advanced setting at study entry (median 208 and 125 d, respectively). 252 pts had subsequent disease progression, treatment discontinuation on immediate subsequent therapy, or died. Proportionally fewer pts in the PAL+FUL vs PBO+FUL arm discontinued next-line treatment (33% vs 46%), indicating that PAL does not adversely affect the efficacy of subsequent treatments. Analysis of the time to end of next-line treatment showed that the HR between the 2 treatment arms was 0.623 ([95% CI, 0.482–0.805]; 1-sided P value=0.0001) in favor of PAL treatment (Table 1).
Conclusion: The current analysis demonstrated that the treatment effect of PAL+FUL was retained in the most immediate line postprogression and that progression after PAL has no effect on the therapeutic benefit from subsequent treatments.
Sponsor: Pfizer
Table 1. PAL+FUL (n=347)PBO+FUL (n=174)Pts who progressed and were eligible for subsequent therapy, n (%)198 (57)130 (75)Pt with postprogression event, n (%)156 (45)96 (55)Objective progression on next-line therapy, n (%)15 (4)5 (3)Deaths, n (%)28 (8)11 (6)End of next-line therapy, n (%)113 (33)80 (46)Median (95% CI) probability of being event-free at 12 mo69.2 (64.0–73.8)54.4 (46.4–61.7)Median (95% CI) time to end of next-line therapy, mo17.9 (16.0–NR)12.8 (11.0–14.6)Hazard ratio (95% CI)0.623 (0.482–0.805)P value0.0001FUL=fulvestrant; NR=not reached; PAL=palbociclib; PBO=placebo.
Citation Format: Turner NC, André F, Cristofanilli M, Verma S, Iwata H, Loi S, Harbeck N, Ro J, Colleoni M, Zhang K, Huang Bartlett C, Giorgetti C, Slamon D. Treatment postprogression in women with endocrine-resistant HR+/HER2- advanced breast cancer who received palbociclib plus fulvestrant in PALOMA-3 [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P4-22-06.