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Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C

Title: Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C
Authors: Lisa Salvatore; Fausto Meriggi
Contributors: Fakih, Marwan G.; Salvatore, Lisa; Esaki, Taito; Modest, Dominik P.; Lopez-Bravo, David P.; Taieb, Julien; Karamouzis, Michalis V.; Ruiz-Garcia, Erika; Kim, Tae-Won; Kuboki, Yasutoshi; Meriggi, Fausto Angelo; Cunningham, David; Yeh, Kun-Huei; Chan, Emily; Chao, Joseph; Saportas, Yaneth; Tran, Qui; Cremolini, Chiara; Pietrantonio, Filippo
Publication Year: 2023
Collection: Università Cattolica del Sacro Cuore: PubliCatt
Subject Terms: colorectal cancer; Settore MED/06 - ONCOLOGIA MEDICA
Description: BACKGROUND KRAS G12C is a mutation that occurs in approximately 3 to 4% of patients with meta- static colorectal cancer. Monotherapy with KRAS G12C inhibitors has yielded only modest efficacy. Combining the KRAS G12C inhibitor sotorasib with panitumumab, an epidermal growth factor receptor (EGFR) inhibitor, may be an effective strategy. METHODS In this phase 3, multicenter, open-label, randomized trial, we assigned patients with chemorefractory metastatic colorectal cancer with mutated KRAS G12C who had not received previous treatment with a KRAS G12C inhibitor to receive sotora- sib at a dose of 960 mg once daily plus panitumumab (53 patients), sotorasib at a dose of 240 mg once daily plus panitumumab (53 patients), or the investigator’s choice of trifluridine–tipiracil or regorafenib (standard care; 54 patients). The primary end point was progression-free survival as assessed by blinded indepen- dent central review according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Key secondary end points were overall survival and objective response. RESULTS After a median follow-up of 7.8 months (range, 0.1 to 13.9), the median progression- free survival was 5.6 months (95% confidence interval [CI], 4.2 to 6.3) and 3.9 months (95% CI, 3.7 to 5.8) in the 960-mg sotorasib–panitumumab and 240-mg sotorasib– panitumumab groups, respectively, as compared with 2.2 months (95% CI, 1.9 to 3.9) in the standard-care group. The hazard ratio for disease progression or death in the 960-mg sotorasib–panitumumab group as compared with the standard-care group was 0.49 (95% CI, 0.30 to 0.80; P=0.006), and the hazard ratio in the 240-mg sotora- sib–panitumumab group was 0.58 (95% CI, 0.36 to 0.93; P=0.03). Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0% (95% CI, 0.0 to 6.6) in the 960-mg sotorasib–panitum- umab, 240-mg sotorasib–panitumumab, and standard-care groups, respectively. Treatment-related adverse events of grade 3 or higher ...
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/37870968; info:eu-repo/semantics/altIdentifier/wos/WOS:001093477800001; volume:389; issue:23; firstpage:2125; lastpage:2139; numberofpages:15; issueyear:2023; journal:THE NEW ENGLAND JOURNAL OF MEDICINE; https://hdl.handle.net/10807/278196
DOI: 10.1056/NEJMoa2308795
Availability: https://hdl.handle.net/10807/278196; https://doi.org/10.1056/NEJMoa2308795
Accession Number: edsbas.756DEBDE
Database: BASE