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List of authors.- John H. Strickler, M.D.,
- Hironaga Satake, M.D., Ph.D.,
- Thomas J. George, M.D.,
- Rona Yaeger, M.D.,
- Antoine Hollebecque, M.D.,
- Ignacio Garrido-Laguna, M.D., Ph.D.,
- Martin Schuler, M.D.,
- Timothy F. Burns, M.D., Ph.D.,
- Andrew L. Coveler, M.D.,
- Gerald S. Falchook, M.D.,
- Mark Vincent, M.D.,
- Yu Sunakawa, M.D., Ph.D.,
- Laetitia Dahan, M.D.,
- David Bajor, M.D.,
- Sun-Young Rha, M.D., Ph.D.,
- Charlotte Lemech, M.D.,
- Dejan Juric, M.D.,
- Marko Rehn, Ph.D.,
- Gataree Ngarmchamnanrith, M.D.,
- Pegah Jafarinasabian, M.D., Ph.D.,
- Qui Tran, Ph.D.,
- and David S. Hong, M.D.
Abstract
Background
KRAS p.G12C mutation occurs successful astir 1 to 2% of pancreatic cancers. The information and efficacy of sotorasib, a KRAS G12C inhibitor, successful antecedently treated patients with KRAS p.G12C–mutated pancreatic crab are unknown.
Methods
We conducted a single-group, signifier 1–2 proceedings to measure the information and efficacy of sotorasib attraction successful patients with KRAS p.G12C–mutated pancreatic crab who had received astatine slightest 1 erstwhile systemic therapy. The superior nonsubjective of signifier 1 was to measure information and to place the recommended dose for signifier 2. In signifier 2, patients received sotorasib astatine a dose of 960 mg orally erstwhile daily. The superior extremity constituent for signifier 2 was a centrally confirmed nonsubjective effect (defined arsenic a implicit oregon partial response). Efficacy extremity points were assessed successful the pooled colonisation from some phases and included nonsubjective response, duration of response, clip to nonsubjective response, illness power (defined arsenic an nonsubjective effect oregon unchangeable disease), progression-free survival, and wide survival. Safety was besides assessed.
Results
The pooled colonisation from phases 1 and 2 consisted of 38 patients, each of whom had metastatic illness astatine enrollment and had antecedently received chemotherapy. At baseline, patients had received a median of 2 lines (range, 1 to 8) of therapy previously. All 38 patients received sotorasib successful the trial. A full of 8 patients had a centrally confirmed nonsubjective effect (21%; 95% assurance interval [CI], 10 to 37). The median progression-free endurance was 4.0 months (95% CI, 2.8 to 5.6), and the median wide endurance was 6.9 months (95% CI, 5.0 to 9.1). Treatment-related adverse events of immoderate people were reported successful 16 patients (42%); 6 patients (16%) had people 3 adverse events. No treatment-related adverse events were fatal oregon led to attraction discontinuation.
Conclusions
Sotorasib showed anticancer enactment and had an acceptable information illustration successful patients with KRAS p.G12C–mutated precocious pancreatic crab who had received erstwhile treatment. (Funded by Amgen and others; CodeBreaK 100 ClinicalTrials.gov number, NCT03600883.)
Funding and Disclosures
Supported by Amgen, a Cancer Center Core Grant (P30 CA 008748 [to Memorial Sloan Kettering Cancer Center]), an M.D. Anderson Cancer Center Support Grant (P30 CA016672), a Clinical Translational Science Award (1UL1 TR003167), and a assistance (RP150535) from the Cancer Prevention Research Institute of Texas Precision Oncology Decision Support Core. The Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy provided molecular and different services.
Disclosure forms provided by the authors are disposable with the afloat substance of this nonfiction astatine NEJM.org.
This nonfiction was published connected December 21, 2022, astatine NEJM.org.
A data sharing statement provided by the authors is disposable with the afloat substance of this nonfiction astatine NEJM.org.
We convey the patients and their families for participating successful the trial; Maya Shehayeb, Pharm.D., Timothy Harrison, Pharm.D., and Jennifer Martucci, B.F.A. (all employed by Amgen), for operational readying assistance; Robert Dawson, B.A., for graphics assistance; and Advait Joshi, Ph.D., of Cactus Life Sciences (part of Cactus Communications) for aesculapian penning enactment with an earlier mentation of the manuscript.
Author Affiliations
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.) — some successful 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.) — some successful 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 astatine 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.).
Dr. Hong tin beryllium contacted astatine [email protected] oregon astatine Investigational Cancer Therapeutics, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0455, Houston, TX 77030.
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