Safety and efficacy of Pazopanib in advanced soft tissue sarcoma: PALETTE (EORTC 62072) subgroup analyses

Abstract

Background: PALETTE is a phase 3 trial that demonstrated single-agent activity of pazopanib in advanced soft tissue sarcomas (aSTS). We performed retrospective subgroup analyses to explore potential relationships between patient characteristics, prior lines of therapy, dose intensity, and dose modifications on safety and efficacy of pazopanib in aSTS.

Methods: PALETTE compared pazopanib with placebo in patients with aSTS (age ≥ 18 years) whose disease had progressed during or following prior chemotherapy. In these subgroup analyses, median progression-free survival (mPFS) among patients receiving pazopanib was the efficacy outcome of interest. Adverse events (AEs) were also compared within subgroups. All analyses were descriptive and exploratory.

Results: A total of 246 patients received pazopanib in the PALETTE study. The mPFS was longer in patients who had only 1 prior line versus 2+ prior lines of therapy (24.7 vs 18.9 weeks, respectively); AE rates were similar regardless of number of prior lines of therapy. The mPFS was similar in patients aged < 65 and ≥ 65 y (20.0 and 20.1 weeks, respectively). Although AEs leading to study discontinuation were higher in older patients (≥65 y, 30%; < 65 y, 17%), rates of dose reductions, dose interruptions, and serious AEs were similar between the 2 age groups. No reduction in mPFS was noted in patients requiring dose reductions or dose interruptions to manage toxicities.

Conclusions: Longer mPFS was observed in patients receiving pazopanib following only 1 line of therapy. Additionally, mPFS with pazopanib was maintained regardless of patient age or dose modifications used to manage toxicity.

Trial registration: NCT00753688 , first posted September 16, 2008 (registered prospectively).

Keywords: Advanced soft tissue sarcoma; PALETTE subgroup analysis; Pazopanib; Progression-free survival.

Conflict of interest statement

ALC received honoraria from Pfizer, Lilly, Amgen, Novartis, PharmaMar, and Bayer.

SB received grants/research support from Novartis, Incyte, and Blueprint Medicine; received honoraria or consultation fees from Novartis, Lilly, Pfizer, PharmaMar, Deciphera, Bayer, and Nanobiotix.

GDD received consulting fees from Novartis, Pfizer, EMD-Serono, Sanofi Oncology, Janssen Oncology, Ignyta, Loxo Oncology, Mirati Therapeutics, Epizyme, PharmaMar, Daiichi-Sankyo, WIRB Copernicus Group, Ziopharm, and Polaris Pharmaceuticals; received research support to Dana-Farber from Bayer, Novartis, Pfizer, Janssen Oncology, Ignyta, Loxo Oncology, AbbVie, Epizyme, and Adaptimmune; patent licensed to Novartis from Dana-Farber with royalty paid to Dana-Farber; member, Board of Directors, Blueprint Medicines and Merrimack Pharmaceuticals; member, Scientific Advisory Board with consulting fees and equity, Blueprint Medicines and Merrimack Pharmaceuticals; consultant, Scientific Advisory Board with consulting fees and equity, G1 Therapeutics, Caris Life Sciences, and Champions Oncology; consultant with equity, Bessor Pharmaceuticals.

GH, LD, and QA are employees of Novartis Pharmaceuticals Corporation.

J-YB received research support and honoraria from Novartis and GSK.

IJ received honoraria from GSK for giving lectures at industry sponsored symposia.

PH received grants from Novartis; honoraria and consultation fees from GSK, Lilly, Pfizer, AROG, and PharmaMar.

PS received institutional support from providing consulting or an advisory role for 6th Element Capital, Adaptimmune, Amcure, Blueprint Medicines, BMS, Deciphera, Eisai, Eli Lilly, Ellipses Pharma, Epizyme, Genzyme, Ipsen, Loxo Oncology, Medpace, Merck, Nektar, Piqur Therapeutics, and Plexxikon; received institutional support for speaker’s bureau from Eisai, PharmaMar, and Eli Lilly; received institutional support (research funding) from Blueprint Medicines, Boehringer Ingelheim, Cobiores nv, Eisai, Eli Lilly, Exelixis, G1Therapeutics, Novartis, PharmaMar, and Plexxikon; received institutional support for travel, accommodation, and expenses from 6th Element Capital, Adaptimmune, Amcure, AstraZeneca, Bayer, Blueprint Medicines, BMS, Boehringer Ingelheim, Daiichi Sankyo, Eisai, Eli Lilly, Epizyme, Genzyme, GSK, Ipsen, Loxo Oncology, Medpace, Nektar, Novartis, PharmaMar, Philogen, Piqur Therapeutics, and Plexxikon.

MA and HG declare that they have no competing interests.