• John H Strickler, Hironaga Satake, Thomas J George, Rona Yaeger, Antoine Hollebecque, Ignacio Garrido-Laguna, Martin Schuler, Timothy F Burns, Andrew L Coveler, Gerald S Falchook, Mark Vincent, Yu Sunakawa, Laetitia Dahan, David Bajor, Sun-Young Rha, Charlotte Lemech, Dejan Juric, Marko Rehn, Gataree Ngarmchamnanrith, Pegah Jafarinasabian, Qui Tran, and David S Hong.
• From Duke University Medical Center, Durham, NC (J.H.S.); Kansai Medical University, Shinmachi, Hirakata (H.S.), and St. Marianna University School of Medicine, Kawasaki (Y.S.) - both in Japan; University of Florida, Gainesville (T.J.G.); Memorial Sloan Kettering Cancer Center, New York (R.Y.); Gustave Roussy Cancer Center, Université Paris-Saclay, Villejuif (A.H.), and Marseille University Hospital, Marseille (L.D.) - both in France; Huntsman Cancer Institute, University of Utah, Salt Lake City (I.G.-L.); West German Cancer Center, University Hospital Essen, Essen (M.S.); University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh (T.F.B.); Fred Hutchinson Cancer Center, University of Washington, Seattle (A.L.C.); Sarah Cannon Research Institute at HealthONE, Denver (G.S.F.); London Regional Cancer Program, London, ON, Canada (M.V.); University Hospitals Cleveland Medical Center, Cleveland (D.B.); Yonsei Cancer Center, Seoul, South Korea (S.-Y.R.); Scientia Clinical Research and Prince of Wales Clinical School, University of New South Wales, Sydney (C.L.); Massachusetts General Cancer Center, Boston (D.J.); Amgen, Thousand Oaks, CA (M.R., G.N., P.J., Q.T.); and University of Texas M.D. Anderson Cancer Center, Houston (D.S.H.).
• N. Engl. J. Med. 2023 Jan 5; 388 (1): 334333-43.

BackgroundKRAS p.G12C mutation occurs in approximately 1 to 2% of pancreatic cancers. The safety and efficacy of sotorasib, a KRAS G12C inhibitor, in previously treated patients with KRAS p.G12C-mutated pancreatic cancer are unknown.MethodsWe conducted a single-group, phase 1-2 trial to assess the safety and efficacy of sotorasib treatment in patients with KRAS p.G12C-mutated pancreatic cancer who had received at least one previous systemic therapy. The primary objective of phase 1 was to assess safety and to identify the recommended dose for phase 2. In phase 2, patients received sotorasib at a dose of 960 mg orally once daily. The primary end point for phase 2 was a centrally confirmed objective response (defined as a complete or partial response). Efficacy end points were assessed in the pooled population from both phases and included objective response, duration of response, time to objective response, disease control (defined as an objective response or stable disease), progression-free survival, and overall survival. Safety was also assessed.ResultsThe pooled population from phases 1 and 2 consisted of 38 patients, all of whom had metastatic disease at enrollment and had previously received chemotherapy. At baseline, patients had received a median of 2 lines (range, 1 to 8) of therapy previously. All 38 patients received sotorasib in the trial. A total of 8 patients had a centrally confirmed objective response (21%; 95% confidence interval [CI], 10 to 37). The median progression-free survival was 4.0 months (95% CI, 2.8 to 5.6), and the median overall survival was 6.9 months (95% CI, 5.0 to 9.1). Treatment-related adverse events of any grade were reported in 16 patients (42%); 6 patients (16%) had grade 3 adverse events. No treatment-related adverse events were fatal or led to treatment discontinuation.ConclusionsSotorasib showed anticancer activity and had an acceptable safety profile in patients with KRAS p.G12C-mutated advanced pancreatic cancer who had received previous treatment. (Funded by Amgen and others; CodeBreaK 100 ClinicalTrials.gov number, NCT03600883.).Copyright © 2022 Massachusetts Medical Society.

28 keywords...

hide…