|The following article features coverage from the Connective Tissue Oncology Society 2021 virtual meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Ripretinib confers a lasting survival benefit over placebo as fourth-line treatment for gastrointestinal stromal tumors (GIST), according to updated data from the phase 3 INVICTUS study.1
The data were presented at the Connective Tissue Oncology Society (CTOS) 2021 Annual Meeting by Robin L. Jones, MBBS, MD, of The Royal Marsden NHS Foundation Trust and Institute of Cancer Research in London.
“These more mature data continue to support the clinically meaningful benefit in progression-free survival and overall survival for ripretinib, with an acceptable safety profile in patients with advanced GIST previously treated with 3 or more prior tyrosine kinase inhibitors,” Dr Jones said.
The INVICTUS trial (ClinicalTrials.gov Identifier: NCT03353753) enrolled 129 patients with advanced GIST who had previously received imatinib, sunitinib, and regorafenib. At baseline, the patients’ median age was 60 years (range, 29-83 years), 57% were men, and 37% had received 4 or more prior therapies (range, 4-7).
The patients were randomly assigned to receive ripretinib (n=85) or placebo (n=44) until disease progression or unblinding. After that, patients from the ripretinib arm could continue on ripretinib at 150 mg per day, have their dose escalated to 150 mg twice a day, or discontinue study treatment.
After progression or unblinding, patients from the placebo arm could cross over to receive ripretinib at 150 mg per day or discontinue study treatment. If these patients had disease progression on ripretinib, they could continue on ripretinib at 150 mg per day, have their dose escalated to 150 mg twice a day, or discontinue study treatment.
In the primary analysis,2 the data cutoff was May 31, 2019. The median follow-up was 6.3 months in the ripretinib arm and 1.6 months in the placebo arm.
The current analysis includes data from 19 months after the primary analysis data cutoff, with a new cutoff of January 15, 2021.
Progression-free survival (PFS) remained significantly longer with ripretinib than with placebo. The median PFS was 6.3 months and 1.0 month, respectively (hazard ratio, 0.16; 95% CI, 0.10-0.27).
In the ripretinib arm, the 6-month PFS rate was 51.0%, the 12-month PFS was 22.2%, and the 18-month PFS was 11.8%. In the placebo arm, the 6-month PFS rate was 3.2%, and the 12-month and 18-month PFS rates were not evaluable.
The objective response rate was 11.8% with ripretinib and 0% with placebo. The median duration of response with ripretinib was 14.5 months.
Overall survival (OS) was significantly longer with ripretinib than with placebo. The median OS was 18.2 months with ripretinib and 6.3 months with placebo. Among patients who crossed over from placebo to ripretinib, the median OS was 10.0 months.
The 6-month OS rate was 84.3% with ripretinib and 55.9% with placebo. The 12-month OS was 65.1% and 29.7%, respectively. The 24-month OS was 42.8% and 19.8%, respectively.
Treatment-emergent adverse events occurred more frequently with ripretinib than with placebo — 52% and 5%, respectively. The most common grade 3-4 adverse events seen with ripretinib were anemia (11%), abdominal pain (7%), and hypertension (7%).
Dr Jones concluded that these data demonstrated stable median PFS, with no change since the primary analysis, and improved median OS among patients receiving ripretinib.
Disclosures: The INVICTUS trial is sponsored by Deciphera Pharmaceuticals LLC. Dr Jones did not report any disclosures.
Read more of Cancer Therapy Advisor’s coverage of CTOS 2021 by visiting the conference page.
- Jones RL Heinrich M, George S, et al. Clinical benefit with ripretinib as ≥4th-line treatment in patients with advanced gastrointestinal stromal tumor: Long-term update from the phase 3 INVICTUS study. Presented at CTOS 2021; November 10-13, 2021. Abstract 10.
- Blay JY, Serrano C, Heinrich MC, et al. Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2020;21(7):923-934. doi:10.1016/S1470-2045(20)30168-6