Health-related quality of life in patients with KRASG12C-mutated chemorefractory metastatic colorectal cancer treated with sotorasib plus panitumumab or standard of care (CodeBreaK 300): results from a phase 3, randomised clinical trial
Dominik Paul Modest, Marwan Fakih, Lisa Salvatore, Taito Esaki, D. Páez López-Bravo, Julien Taı̈eb, Michalis V. Karamouzis, Erika Ruíz‐García, Tae Won Kim, Yasutoshi Kuboki, Fausto Meriggi, David Cunningham, Kun‐Huei Yeh, Chiara Cremolini, Qui Tran, Emily Chan, Joseph Chao, István Májer, Filippo Pietrantonio
Abstract
BACKGROUND: -mutated chemorefractory metastatic colorectal cancer. This analysis evaluated patient-reported outcomes (PROs) as secondary and exploratory endpoints. METHODS: [up to 80 mg per dose] on days 1-5 and 8-12 twice a day, orally) or regorafenib (160 mg daily for the first 21 days, orally). Randomisation was stratified by by previous anti-angiogenic therapy, time from initial diagnosis of metastatic disease to randomisation, and ECOG performance status. The primary endpoint was progression-free survival (reported previously). PROs included fatigue at its worst according to the Brief Fatigue Inventory, pain at its worst according to the Brief Pain Inventory (where lower score is better), and Global Health Status-Quality of Life (GHS-QoL) and physical function subscales of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (where higher score is better) assessed via validated PRO questionnaires, administered at baseline, day 1 of each 4-week cycle until disease progression, and safety follow-up. Analyses were conducted in a modified intention-to-treat population. Least squares mean changes from baseline to week 9 were estimated using a mixed effects model for repeated measures. Time to deterioration (TTD), change in overall status, and patient-reported tolerability were also evaluated as prespecified exploratory outcomes. TTD was summarised using a stratified Cox proportional hazards model and Kaplan-Meier curve. Change in overall status and patient-reported tolerability were also summarised descriptively over time. The study is registered with ClinicalTrials.gov, NCT05198934, and prespecified analyses are completed. FINDINGS: Between April 19, 2022, and March 14, 2023, 160 patients were enrolled and randomly assigned to receive sotorasib 960 mg-panitumumab (n=53), sotorasib 240 mg-panitumumab (n=53), and investigator's choice (n=54). Median duration of treatment was 6·0 months (IQR 3·7-7·0), 4·6 months (3·3-6·2), and 2·2 months (1·8-4·2) in these groups, respectively. 81 (51%) patients in the study were female; 109 (68%) patients were White, 40 (25%) were Asian, one (1%) was Black, and ten (6%) were of another race or not reported; 12 (8%) were Hispanic or Latino and three (2%) were of unknown ethnicity. Compliance rates for PRO assessments at week 9 were high (approximately 80%) and similar across treatment groups. Least squares mean changes in PROs at week 9 favoured the two sotorasib groups. Differences in changes from baseline for sotorasib 960 mg-panitumumab and sotorasib 240 mg-panitumumab (both vs investigator's choice), respectively were: -0·89 (95% CI -1·80 to 0·01) and -0·58 (-1·47 to 0·30) for fatigue at its worst, -1·45 (-2·32 to -0·58) and -1·14 (-2·00 to -0·28) for pain at its worst, 9·43 (2·31 to 16·56) and 6·49 (-0·43 to 13·41) for GHS-QoL, and 5·38 (-0·01 to 10·78) and 6·34 (1·07 to 11·62) for physical function. INTERPRETATION: -mutated chemorefractory metastatic colorectal cancer. FUNDING: Amgen.