Correction: Activity and Safety of Palbociclib in Patients with Advanced Gastrointestinal Stromal Tumors Refractory to Imatinib and Sunitinib: A Biomarker-driven Phase II Study.

Abstract

Purpose: CDKN2A loss is frequent in GIST and associated with aggressive outcome. Palbociclib is a CDK4 inhibitor with preclinical anti-tumor efficacy in tumors with P16/CDKN2A loss. Methods: This is a multicenter single-arm phase 2 clinical trial assessing safety and efficacy of Palbociclib in patients (pts) with advanced GIST bearing CDKN2A gene loss. Adults with unresectable locally advanced or metastatic, refractory to previously treated with at least Imatinib and Sunitinib, measurable and documented progressive disease (PD) as per RECIST 1.1, and CDKN2A deletion centrally assessed were eligible. Pts received Palbociclib 125mg orally daily on a 21 days on / 7 days off dosing schedule, until PD or unacceptable toxicity. The primary endpoint was 4-month non-PD rate according to RECIST 1.1. Results: As of May 2017, 71 pts had been included in the study, and 29 pts (40.3%) met the molecular eligibility requirement. Twenty five pts (86.2%) had grade 1-2 adverse events (AE) and 12 pts (41.4%)grade 3-4 AE possibly related to the drug. The planned interim statistical analysis performed after central histological and radiological review showed that 19 (86.4%) out of the first 22 evaluable pts had PD at 4 months. CDKN2A status had no impact either on overall survival or outcome on previous standard lines of treatment. Translational analysis suggested up-regulation of CCNE1 or down-regulation of CDKN1A/P21 or LRRC3B as potential mechanisms of resistance. Conclusion: Palbociclib has no significant clinical activity as a single agent in P16/CDKN2A deleted GIST refractory to Imatinib and Sunitinib.