Cancer Res Commun. 2023 Sep 20. doi: 10.1158/2767-9764.CRC-23-0084. Online ahead of print.
ABSTRACT
PURPOSE: RTOG 0617 was a Phase III randomized trial for patients with unresectable stage IIIA/IIIB non-small-cell lung cancer comparing standard-dose (60Gy) versus high-dose (74Gy) radiotherapy and chemotherapy, plus or minus cetuximab. Although the study was negative, based on prior evidence that patients with the KRAS-variant, an inherited germline mutation, benefit from cetuximab, we evaluated KRAS-variant patients in RTOG 0617.
EXPERIMENTAL DESIGN: From RTOG 0617 328/496 (66%) of patients were included in this analysis. For time-to-event outcomes, stratified log-rank tests and multivariable Cox regression models were used. For binary outcomes, Cochran-Mantel-Haenzel tests and multivariable logistic regression models were used. All statistical tests were two-sided, and a p-value <0.05 was considered significant.
RESULTS: A total of 17.1% (56/328) of patients had the KRAS-variant, and overall survival rates were similar between KRAS-variant and non-variant patients. However, there was a time-dependent effect of cetuximab seen only in KRAS-variant patients – while the hazard of death was higher in cetuximab treated patients within year one (HR=3.37, 95% CI: 1.13-10.10, p=0.030), death was lower from year one to four (HR=0.33, 95% CI: 0.11-0.97, p=0.043). In contrast, in non-variant patients, the addition of cetuximab significantly increased local failure (HR=1.59, 95% CI: 1.11-2.28, p=0.012).
CONCLUSIONS/DISCUSSION: Although an overall survival advantage was not achieved in KRAS-variant patients, there is potential impact of cetuximab for this genetic subset of patients. In contrast, cetuximab seems to harm non-variant patients. These findings further support the importance of genetic patient selection in trials studying the addition of systemic agents to radiotherapy.
PMID:37728512 | DOI:10.1158/2767-9764.CRC-23-0084
