Continued Sunitinib Treatment After Progressive Disease (PD) in a Worldwide Treatment-Use Trial of Patients (PTS) With Gastrointestinal Stromal Tumor (GIST)

ABSTRACT Background Continuous kinase inhibition has been posited as important for optimizing outcomes of pts with kinase-mutant-driven cancers such as GIST. The outcomes of pts who continued on treatment after PD vs those who stopped after PD were compared using data from a worldwide treatment-use study of sunitinib in GIST. Methods This open-label study was designed to provide access to and assess the safety and efficacy of sunitinib (starting dosing schedule: 50 mg/d; 4 wk on treatment, 2 wk off in 6-wk cycles) in pts with advanced imatinib-resistant/intolerant GIST (enrollment: 9/2004 - 12/2007). Treatment was continued for as long as there was evidence of disease control in the judgment of the investigator; survival was monitored for ≤2 y post-treatment or until 7/2008, whichever came first. In this post hoc analysis, pts were dichotomized based on whether sunitinib treatment was continued or stopped after PD. Results At final data cutoff (10/2011), 1124 of 1131 pts enrolled had received ≥1 dose of sunitinib on study. Of these pts, 380 continued and 324 stopped sunitinib treatment after PD. The groups were generally well balanced for baseline demographics except for gender (proportion male: 67% vs 59%) and pts with ECOG PS 0 (44% vs 35%). Pts who continued on treatment after PD generally received sunitinib longer than those who did not continue post-PD (median 9 vs 4 cycles started). Median OS among pts who remained on treatment after PD was 22.8 months (95% CI: 20.4 - 24.7) and 13.2 months (95% CI: 11.7 - 14.5) among those who did not continue sunitinib after PD. The most common treatment-related AEs in both groups were diarrhea, fatigue, and hand - foot syndrome, which were mainly grade 1/2 and occurred at a higher rate among pts who continued sunitinib after PD than among those who stopped treatment after PD (49% vs 35%; 48% vs 41%; and 39% vs 31%, respectively). Conclusions Results of this analysis suggest that pts with GIST who continued on sunitinib after PD exhibited a better clinical outcome (longer OS) than those who stopped treatment after PD, although the potential impact of differing pt characteristics and selection bias cannot be ruled out in this retrospective analysis. Disclosure P. Reichardt: Compensated advisory relationship: Pfizer, Novartis and Bayer. Honoraria: Pfizer and Novartis. Research funding: Pfizer and Novartis. Y. Kang: Compensated advisory relationship: Pfizer and Novartis. Honararia: Pfizer and Novartis. Research funding: Novartis. P. Rutkowski: Compensated advisory relationship: Novartis, BMS and MSD. Honoraria: Novartis, Pfizer, MSD, BMS and Roche. L.S. Rosen: Research funding: Pfizer. B. Seddon: Compensated advisory relationship: Pfizer. Honoraria: Pfizer. L. Chen: Compensated employment: Pfizer. Stock ownership: Pfizer. K. Fly: Compensated employment: Pfizer. Stock ownership: Pfizer. G. Demetri: Compensated advisory relationship: Pfizer and Novartis. Honoraria: Pfizer and Novartis. Research funding: Pfizer, Novartis and Bayer. Expert testimony: Pfizer, Novartis, and Infinity. All other authors have declared no conflicts of interest.