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Zalcberg JR , Heinrich MC , George S , Bauer S , Schöffski P , Serrano C , Gelderblom H , Jones RL , Attia S , D'Amato G , Chi P , Reichardt P , Somaiah N , Meade J , Reichert V , Shi K , Sherman ML , Ruiz-Soto R , von Mehren M , Blay JY
Clinical Benefit of Ripretinib Dose Escalation After Disease Progression in Advanced Gastrointestinal Stromal Tumor: An Analysis of the INVICTUS Study
Oncologist. 2021 Jul 27
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BACKGROUND: Ripretinib 150 mg once daily (QD) is indicated for advanced gastrointestinal stromal tumor (GIST) as ≥fourth-line therapy. In INVICTUS, ripretinib intra-patient dose escalation (IPDE) to 150 mg twice daily (BID) was allowed after progressive disease (PD) on 150 mg QD by blinded independent central review using modified RECIST 1.1. We report the efficacy and safety of ripretinib IPDE to 150 mg BID after PD among patients randomized to ripretinib 150 mg QD in the INVICTUS study. MATERIALS AND METHODS: Tumor imaging was performed every 28-day cycle for the first 4 cycles in the ripretinib 150 mg QD period and then every other cycle, including the 150 mg BID period. Among the ripretinib IPDE patients, progression-free survival (PFS)1 was the time from randomization until PD; PFS2 was the time from the first dose of ripretinib 150 mg BID to PD or death. RESULTS: Among 43 ripretinib IPDE patients, median PFS1 was 4.6 months (95% confidence interval [CI], 2.7-6.4) and median PFS2 was 3.7 months (95% CI, 3.1-5.3). Median overall survival was 18.4 months (95% CI, 14.5-not estimable). Ripretinib 150 mg BID (median duration of treatment 3.7 months) was well tolerated with new or worsening Grade 3-4 TEAEs of anemia in 6 (14%) and abdominal pain in 3 (7%) patients. Ripretinib 150 mg BID was discontinued due to TEAEs in 7 (16%) patients. CONCLUSION: Ripretinib 150 mg BID after PD on 150 mg QD may provide additional clinically meaningful benefit with an acceptable safety profile in patients with ≥fourth-line GIST. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT03353753 (INVICTUS) IMPLICATIONS FOR PRACTICE: Of the 85 patients with advanced gastrointestinal stromal tumor having received ≥3 prior anticancer therapies randomized to ripretinib 150 mg once daily (QD) in the phase 3 INVICTUS study, 43 underwent ripretinib intra-patient dose escalation (IPDE) to 150 mg twice daily (BID) after progressive disease (PD). Median progression-free survival was 4.6 months before and 3.7 months after ripretinib IPDE. The safety profile of ripretinib 150 mg BID was acceptable. These findings indicate ripretinib IPDE to 150 mg BID may provide additional clinical benefit in patients with PD on ripretinib 150 mg QD, for whom limited treatment options exist.
1549-490x Zalcberg, John R Orcid: 0000-0002-6624-0782 Heinrich, Michael C George, Suzanne Bauer, Sebastian Schöffski, Patrick Serrano, César Gelderblom, Hans Jones, Robin L Attia, Steven D'Amato, Gina Chi, Ping Reichardt, Peter Somaiah, Neeta Meade, Julie Reichert, Vienna Shi, Kelvin Sherman, Matthew L Ruiz-Soto, Rodrigo von Mehren, Margaret Blay, Jean-Yves Journal Article United States Oncologist. 2021 Jul 27. doi: 10.1002/onco.13917.