Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC.
| Autor: | Hochmair MJ; Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria. Electronic address: maximilian.hochmair@gesundheitsverbund.at., Vermaelen K; Department of Pulmonary Medicine, Ghent University Hospital, Ghent, Oost-Vlaanderen, Belgium., Mountzios G; Department of Medical Oncology and Clinical Trials Unit, Henry Dunant Hospital Center, Athens, Greece., Carcereny E; Medical Oncology Department, Catalan Institute of Oncology Badalona, Badalona Applied Research Group in Oncology, Badalona, Barcelona, Spain., Dooms C; Department of Respiratory Diseases, University Hospitals KU Leuven, Leuven, Belgium., Lee SH; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea., Morocz E; Pulmonology Hospital, Törökbálint, Hungary., Kato T; Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan., Ciuleanu TE; Institutul Oncologic Prof Dr Ion Chiricuta and University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania., Dy GK; Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA., Parente B; Pulmonology Department, Hospital CUF Porto, Porto, Portugal., O'Byrne KJ; Princess Alexandra Hospital, Translational Research Institute and Queensland University of Technology, Brisbane, Queensland, Australia., Chu QS; Division of Medical Oncology, Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada., Castro Junior G; Hospital Sírio Libanês, São Paulo, Brazil., Girard N; Institut du Thorax Curie Montsouris, Institut Curie, Paris, France; UVSQ, Paris Saclay, Versailles, France., Snyder W; Amgen Inc., Thousand Oaks, CA, USA., Tran Q; Amgen Inc., Thousand Oaks, CA, USA., Kormany W; Amgen Inc., Thousand Oaks, CA, USA., Houk B; Amgen Inc., Thousand Oaks, CA, USA., Mehta B; Amgen Inc., Thousand Oaks, CA, USA., Curioni-Fontecedro A; Department of Medical Oncology and Hematology, University Hospital Zurich, Zurich, Switzerland; University of Fribourg and Hospital of Fribourg, Fribourg, Switzerland. |
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| Jazyk: | angličtina |
| Zdroj: | European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2024 Sep; Vol. 208, pp. 114204. Date of Electronic Publication: 2024 Jul 05. |
| DOI: | 10.1016/j.ejca.2024.114204 |
| Abstrakt: | Background: Sotorasib 960 mg once daily is approved to treat KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC). Sotorasib exhibits non-dose proportional pharmacokinetics and clinical responses at lower doses; therefore, we evaluated the efficacy and safety of sotorasib 960 mg and 240 mg. Methods: In this phase 2, randomized, open-label study, adults with KRAS G12C-mutated advanced NSCLC received sotorasib 960 mg or 240 mg once daily. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and pharmacokinetics. The study was not powered for formal statistical hypothesis testing. Results: In the 960 mg group (n = 104), ORR was 32.7 % and DCR was 86.5 %. In the 240 mg group (n = 105), ORR was 24.8 % and DCR was 81.9 %. Median PFS was 5.4 months (960 mg) and 5.6 months (240 mg). At a median follow-up of 17.5 months, median OS was 13.0 months (960 mg) and 11.7 months (240 mg). AUC Conclusions: Patients treated with sotorasib 960 mg once daily had numerically higher ORR and DCR, and longer DOR and OS, than patients treated with 240 mg in this descriptive analysis. TEAEs were manageable with label-directed dose modifications. Clinical Trial Registration: NCT03600883. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. J. Hochmair: Financial Interests, Personal, Other, Consulting or Advisory role: Takeda, Roche, Lilly, AstraZeneca/Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Lilly, MSD Oncology, Novartis, Roche, Amgen. K. Vermaelen: Financial Interests, Personal, Research Grant: Bristol Myers Squibb (BMS); Financial Interests, Personal, Other, Honoraria: BMS; Financial Interests, Personal, Other, Support for Attending Meetings: AstraZeneca, BMS, Merck; Financial Interests, Personal, Other, Patents Planned/Issued/Pending: Ghent University; Financial Interests, Personal, Other, Data Safety Monitoring Board or Advisory Board: Amgen, AstraZeneca, BMS, Merck. G. Mountzios: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca, BMS GmbH & Co. KG, Boehringer Ingelheim, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Other, Consulting or Advisory Board: Amgen, AstraZeneca/Greece, BMS GmbH & Co. KG, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, MSD; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, BMS GmbH & Co. KG, Ipsen, MSD, Novartis, Roche. E. Carcereny: No conflicts to disclose. C. Dooms: No conflicts to disclose. S.-H. Lee: Financial Interests, Personal, Other, Honoraria: Amgen, AstraZeneca/MedImmune, Lilly, Merck, Roche; Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, BMS/Ono, IMBdx, Janssen, Lilly, Merck, Pfizer, Roche, Takeda; Financial Interests, Personal, Research Grant: AstraZeneca, Lunit, Merck; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis. E. Morocz: No conflicts to disclose. T. Kato: Financial Interests, Personal, Advisory Board, Speaker, Consultancy: AstraZeneca, Eli Lilly, Merck Biopharma, MSD; Financial Interests, Personal, Advisory Board, Speaker: Pfizer, Amgen, Janssen; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo, Takeda, Taiho; Financial Interests, Personal, Other, Consultancy, Speaker: Chugai; Financial Interests, Personal, Invited Speaker: Ono, Novartis, BMS, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: BeiGene, GSK; Financial Interests, Personal, Advisory Board, Steering Committee: Roche; Financial Interests, Personal, Full or Part-Time Employment, Family Member: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Chugai, MSD, Pfizer, Eli Lilly, AbbVie, Regeneron, Novartis, Amgen, Merck Biopharma, Haihe Biopharma, Blueprint Medicines, Turning Point, BeiGene, Gilead, GSK, Janssen, Bayer, Takeda, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Local PI: AstraZeneca. T.-E. Ciuleanu: Financial Interests, Personal, Other, Consulting or Advisory Role: Astellas Pharma, Janssen, BMS, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Eli Lilly, AstraZeneca, Merck Sharp & Dohme (MSD), Sanofi, Novartis, Servier, A&D Pharma; Financial Interests, Personal, Other, Travel Support: Pfizer, Sanofi, Boehringer Ingelheim, Merck, Servier, Ipsen, Amgen, A&D Pharma, AstraZeneca, Genentech, BMS, MSD Oncology, Eli Lilly, Janssen, Novartis, Astellas Pharma. G. K. Dy: Financial Interests, Personal, Other, Consulting or Advisory Role: AstraZeneca, Mirati Therapeutics, Lilly, Amgen, Regeneron, Eli Lilly; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Mirati Therapeutics, Lilly, Sanofi, BioAtla, Regeneron, Iovance Biotherapeutics, Revolution Medicines. B. Parente: No conflicts to disclose. K. J. O’Byrne: Financial Interests, Personal, Stocks/Shares: Carpe Vitae Pharmaceuticals, DGC Diagnostics, Replica Pharmaceuticals; Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Ipsen, Janssen-Cilag, Merck Group, MSD, Novartis, Pfizer, Roche, Seagen, Takeda, TriStar, Yuhan; Financial Interests, Personal, Other, Consulting or advisory Role: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, BMS, Ipsen, Janssen-Cilag, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi, Seagen, Yuhan; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: three active patents. Q. S. Chu: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AnHeart Therapeutics, Astellas, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, Jazz Pharmaceutical, Johnson and Johnson, Merck, Novartis, Pfizer, Roche, Takeda. G. De Castro Jr.: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Pfizer, MSD, BMS, Novartis, Roche, Amgen, Janssen, Merck Serono, Daiichi Sankyo, Sanofi, Lilly; Financial Interests, Personal, Other, Consulting or Advisory Role: Boehringer Ingelheim, Pfizer, Bayer, Roche, MSD, BMS, AstraZeneca, Yuhan, Merck Serono, Janssen, Libbs, Sanofi, Novartis, Daiichi Sankyo, Lilly; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bayer, Novartis, Roche, Merck Serono, BMS, MSD, Boehringer Ingelheim, Pfizer, Janssen, Amgen, Lilly, Daiichi Sankyo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD, Novartis, Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bayer, BMS, Merck Serono, Daiichi Sankyo. N. Girard: Financial Interests, Personal, Research Grant: AstraZeneca, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Novartis, Pfizer, Sivan, Trizell; Financial Interests, Personal, Other, Consulting or Advisory Role: BMS, AstraZeneca, AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Hoffmann-La Roche, Janssen, Merck, MSD, Mirati, Novartis, Pfizer, Roche, Sanofi, Sivan; Financial Interests, Personal, Expert Testimony: AstraZeneca; Financial Interests, Personal, Invited Speaker, Participation in Data Safety Monitoring Board: Roche; Financial Interests, Personal, Other, Leadership Role: International Thymic Malignancy Interest Group; Financial Interests, Personal, Full or Part-Time Employment, Employment of a Family Member: AstraZeneca. W. Snyder, Q. Tran, W. Kormany, B. Houk, B. Mehta: Financial Interests, Personal, Full or Part-Time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Curioni-Fontecedro: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Boehringer Ingelheim, MSD, Novartis, Amgen, Roche, Takeda, Janssen; Non-Financial Interests, Personal, Leadership Role: Swiss Academy for Clinical Cancer Research (SAKK); Non-Financial Interests, Personal, Principal Investigator of Clinical Trials: Roche; Non-Financial Interests, Personal, Principal Investigator, Clinical Trials: Takeda, MSD, BMS. (Copyright © 2024. Published by Elsevier Ltd.) |
| Databáze: | MEDLINE |
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