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Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer

Title: Overall Survival Analysis of the Phase III CodeBreaK 300 Study of Sotorasib Plus Panitumumab Versus Investigator's Choice in Chemorefractory KRAS G12C Colorectal Cancer
Authors: Pietrantonio, Filippo; Salvatore, Lisa; Esaki, Taito; Modest, Dominik Paul; Taieb, Julien; Karamouzis, Michalis V.; Ruiz-Garcia, Erika; Kim, Tae Won; Kuboki, Yasutoshi; Cunninghamo, D.; Yeh, Kun Huei; Chan, Emily; Chao, Joseph; Tran, Qui; Cremolini, Chiara; Fakih, Marwan; Paez, David; Meriggi, Fausto; Universitat Autònoma de Barcelona. Departament de Medicina
Publication Year: 2025
Collection: Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB
Subject Terms: Adult; Aged; 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Mutation; Panitumumab; Phenylurea Compounds; Piperazines; Progression-Free Survival; Proto-Oncogene Proteins p21(ras); Pyridines; Pyrimidines; Sulfonamides; Thymine
Description: In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice (trifluridine/tipiracil or regorafenib) in patients with KRAS G12C-mutated chemorefractory metastatic colorectal cancer (mCRC). One hundred sixty patients were randomly assigned 1:1:1 to receive sotorasib 960 mg-panitumumab (n = 53), sotorasib 240 mg-panitumumab (n = 53), or investigator's choice (n = 54; crossover permitted after primary analysis). Overall survival (OS) analysis, a key secondary end point, although not adequately powered, was prespecified at 50% maturity (after approximately 80 deaths). In this study, we report the OS, updated overall response rates (ORRs), and data for safety. After a median follow-up of 13.6 months, 24, 28, and 30 deaths occurred in the sotorasib 960 mg-panitumumab, sotorasib 240 mg-panitumumab, and investigator's choice arms, respectively; updated objective response rates (ORRs; 95% CI) were 30.2% (95% CI, 18.3 to 44.3), 7.5% (95% CI, 2.1 to 18.2), and 1.9% (95% CI, 0.0 to 9.9), respectively. Compared with investigator's choice, the hazard ratios (HRs [95% CI]) for OS were 0.70 (95% CI, 0.41 to 1.18; two-sided P =.20) with sotorasib 960 mg-panitumumab and 0.83 (95% CI, 0.49 to 1.39; two-sided P =.50) with sotorasib 240 mg-panitumumab. No new safety signals were observed. Although not statistically significant, the observed OS HR and ORR along with prior PFS and safety findings support sotorasib 960 mg-panitumumab as a standard of care in patients with chemorefractory KRAS G12C mCRC.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 15277755
Relation: Journal of clinical oncology; Vol. 43, Num. 19 (January 2025), p. 2147-2154; https://ddd.uab.cat/record/325976; urn:oai:ddd.uab.cat:325976; urn:scopus_id:105009122813; urn:articleid:15277755v43n19p2147; urn:pmid:40215429
Availability: https://ddd.uab.cat/record/325976
Rights: open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades. ; https://creativecommons.org/licenses/by-nc-nd/4.0/
Accession Number: edsbas.EF05A173
Database: BASE