Treatment effect of palbociclib plus endocrine therapy by prognostic and intrinsic subtype and biomarker analysis in pat
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CLINICAL TRIAL
Treatment effect of palbociclib plus endocrine therapy by prognostic and intrinsic subtype and biomarker analysis in patients with bone‑only disease: a joint analysis of PALOMA‑2 and PALOMA‑3 clinical trials Richard S. Finn1 · Massimo Cristofanilli2 · Johannes Ettl3 · Karen A. Gelmon4 · Marco Colleoni5 · Carla Giorgetti6 · Eric Gauthier7 · Yuan Liu8 · Dongrui R. Lu8 · Zhe Zhang8 · Cynthia Huang Bartlett9 · Dennis J. Slamon1 · Nicholas C. Turner10 · Hope S. Rugo11 Received: 25 March 2020 / Accepted: 30 June 2020 © The Author(s) 2020
Abstract Purpose This analysis evaluated the relationship between treatment-free interval (TFI, in PALOMA-2)/disease-free interval (DFI, in PALOMA-3) and progression-free survival (PFS) and overall survival (OS, in PALOMA-3), treatment effect in patients with bone-only disease, and whether intrinsic subtype affects PFS in patients receiving palbociclib. Methods Data were from phase 3, randomized PALOMA-2 and PALOMA-3 clinical studies of hormone receptor‒positive/human epidermal growth factor receptor 2‒negative (HR+ /HER2−) advanced breast cancer (ABC) patients receiving endocrine therapy plus palbociclib or placebo. Subpopulation treatment effect pattern plot (STEPP) analysis evaluated the association between DFI and PFS and OS. PFS by luminal subtype and cyclin-dependent kinase (CDK) 4/6 or endocrine pathway gene expression levels were evaluated in patients with bone-only disease; median PFS and OS were estimated by the Kaplan–Meier method. Results Median durations of TFI were 37.1 and 30.9 months (PALOMA-2) and DFI were 49.2 and 52.0 months (PALOMA-3) in the palbociclib and placebo groups, respectively. Among the PALOMA-2 biomarker population (n = 454), 23% had bone-only disease; median PFS was longer with palbociclib versus placebo (31.3 vs 11.2 months; hazard ratio, 0.41; 95% CI 0.25‒0.69). The interaction effect of bone-only versus visceral disease subgroups on median PFS with palbociclib was not significant (P = 0.262). Among the PALOMA-3 biomarker population (n = 302), 27% had bone-only disease. STEPP analyses showed that palbociclib PFS benefit was not affected by DFI, and that palbociclib OS effect may be smaller in patients with short DFIs. Among patients who provided metastatic tumor tissues (n = 142), regardless of luminal A (hazard ratio, 0.23; 95% CI 0.11‒0.47; P = 0.0000158) or luminal B (hazard ratio, 0.26; 95% CI 0.12‒0.56; P = 0.000269) subtype, palbociclib improved PFS versus placebo. Conclusions These findings support palbociclib plus endocrine therapy as standard of care for HR+ /HER2− ABC patients, regardless of baseline TFI/DFI or intrinsic molecular subtype, including patients with bone-only disease. Trial registration Pfizer (clinicaltrials.gov:NCT01740427, NCT01942135). Keywords Bone-only disease · Disease-free interval · Intrinsic subtype · Palbociclib · Treatment-free interval
Carla Giorgetti and Cynthia Huang Bartlett: at the time of the study. * Richard S. Finn [email protected] Extended author information available on the last
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