Highlights from

ESMO 2019

European Society for Medical Oncology Congress 2019

Barcelona 27 September - 01 October 2019

Heavily pre-treated GIST: ripretinib improves PFS

In the double-blinded phase 3 INVICTUS trial, ripretinib (a novel KIT and PDGFRA inhibitor) demonstrated a dramatic improvement in progression-free survival (PFS) compared with placebo in heavily pre-treated patients with heavily advanced gastrointestinal stromal tumours (GIST).

Primary mutations in KIT and PDGFRA drive GIST in approximately 85% of cases, according to presenting author Prof. Margaret von Mehren (Fox Chase Cancer Center, USA) [1]. Ripretinib works as an inhibitor of KIT and PDGFRA.

The INVICTUS trial randomised patients to receive ripretinib at 150 mg daily (n=85) or placebo (n=44). The median age of patients was 60 years, with more aged 75 or more in the placebo group (9% for ripretinib vs 23% for placebo). Two-thirds of patients had received 3 prior therapies, and a third had received more than 4 (range, 4-7). The most common mutation was at KIT exon 11 (58%) followed by KIT exon 9 (16%).

In the study, the median PFS was 6.3 months with ripretinib compared with 1.0 months for placebo, amounting to a 85% reduction in the risk of progression or death (HR 0.15; 95% CI 0.09-0.25; P<0.0001). Additionally, the secondary endpoint of median overall survival was 15.1 for ripretinib vs 6.6 months for placebo (HR 0.36; 95% CI 0.20-0.63; P=0.0004), representing a 64% reduction in the risk of death. However, the hierarchical testing procedures utilised for the study prevented a conclusive establishment of statistical significance for OS.

The 6-month PFS rate was 51.0% (95% CI 39.4%-61.4%) for ripretinib compared with 3.2% for placebo (95% CI 0.2%-13.8%). PFS benefit was observed across all assessed patient subgroups. In those treated with 3 therapies, the HR for PFS was 0.15, in favour of ripretinib (95% CI 0.08-0.29). In those treated with ≥4 therapies, the HR was 0.24, also in favour of ripretinib (95% CI, 0.12-0.51).

"Ripretinib represents a potential new standard of care with broad activity in fourth-line GIST, a patient population with advanced refractory disease and no other approved options," said Prof. von Mehren.

Keywords: INVICTUS; Gastrointestinal Stromal Tumors; Progression-Free Survival; Receptor, Platelet-Derived Growth Factor alpha

  1. von Mehren M et al. ESMO Congress 2019. Abstract LBA87.

Top image: STEVE GSCHMEISSNER / SCIENCE PHOTO LIBRARY

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