As reported in the Journal of Clinical Oncology by Yoon-Koo Kang, MD, and colleagues, the phase III VOYAGER trial showed no improvement in progression-free survival with avapritinib vs regorafenib as third- or later-line treatment of patients with molecularly unselected, locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST).
Avapritinib was approved by the U.S. Food and Drug Administration in January 2020 for treatment of adult patients with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including D842V mutations.
Yoon-Koo Kang, MD
In the open-label trial, 476 patients from sites in North America, Europe, Australia, and Asia were randomly assigned between March 2018 and November 2019 to receive avapritinib at 300 mg once daily continuously (n = 240) or regorafenib at 160 mg once daily 3 weeks on and 1 week off in 28-day cycles as third- or later-line treatment (n = 236). The primary endpoint was progression-free survival on central radiology review. Crossover from regorafenib to avapritinib was permitted upon centrally confirmed disease progression.
Median progression-free survival was 4.2 months in the avapritinib group vs 5.6 months in the regorafenib group (hazard ratio [HR] = 1.25, 95% confidence interval = 0.99–1.57, P = .055). No significant differences were observed among patients receiving third-line therapy (median = 4.2 vs 5.5 months, HR = 1.26, P = .068) or fourth-line therapy (median = 3.8 vs 5.6 months, HR = 1.19, P = .550).
Overall survival data were immature at cutoff, with a median follow-up of 8.5 months in the avapritinib group and 9.6 months in the regorafenib group. A total of 99 patients in the regorafenib group crossed over to receive avapritinib. Estimated overall survival at 12 months was 68.2% vs 67.4%, including 67.9% vs 68.8% in those receiving third-line treatment and 67.4% vs 60.4% in those receiving fourth-line treatment. Objective response rates were 17.1% vs 7.2%, with median durations of response of 7.6 vs 9.4 months.
Treatment-related grade ≥ 3 adverse events occurred in 55% of patients in the avapritinib group vs 58% of the regorafenib group. The most common in the avapritinib group were anemia (21%) and increased bilirubin (5%); the most common in the regorafenib group were palmar-plantar erythrodysesthesia syndrome (16%) and hypertension (12%). Treatment-related serious adverse events occurred in 20% vs 15% of patients. Treatment-related adverse events led to discontinuation of treatment in 8% vs 6%.
The investigators concluded, “[The] primary endpoint was not met. There was no significant difference in median progression-free survival between avapritinib and regorafenib in patients with molecularly unselected late-line GIST.”
Sebastian Bauer, MD, of the West German Cancer Center DKTK-Partner-Site, University of Duisburg-Essen, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Blueprint Medicines Corporation. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.