KEY TAKEAWAYS
- The CodeBreaK 300 phase 3 trial aimed to investigate the impact of sotorasib + pmab on patient-reported outcomes in chemorefractory KRAS G12C-mutated mCRC.
- Researchers noticed that sotorasib demonstrates improved HRQoL and reduced deterioration risk, highlighting its efficacy in chemorefractory mCRC.
CodeBreaK 300 was a phase 3, multicenter, randomized, open-label study. Dominik Paul Modest and the team aimed to investigate the efficacy of sotorasib 960 mg (soto960) + panitumumab (pmab) and sotorasib 240 mg (soto240) + pmab compared to the investigator’s choice of trifluridine/tipiracil (T/T) or regorafenib (rego) in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC).
The study already met its primary endpoint, demonstrating statistically significant improvement in progression-free survival (PFS) with both doses of sotorasib. Patient-reported outcomes (PROs) were evaluated as secondary and exploratory endpoints in this analysis.
Researchers performed an inclusive analysis, comparing changes in PRO scores from study baseline through week 8 for soto960+pmab and soto240+pmab against the control group using a mixed effect model for repeated measures. PRO instruments comprised the Brief Fatigue Inventory, the Brief Pain Inventory, and the European Organisation for Research and Treatment of Cancer Core 30-item Quality of Life questionnaire. Time to deterioration (TTD) was assessed via Kaplan-Meier plots and Cox proportional hazard models. All analyses were conducted on patients with baseline and at least one post-baseline PRO score.
About 160 patients were randomized in a 1:1:1 ratio to soto960+pmab (n=53), soto240+pmab (n=53), or T/T or rego (n=54). Compliance rates for PRO assessments were high (>83%) and remained consistent across all 3 treatment groups. Analysis of least square (LS) mean changes from baseline revealed favorable outcomes in fatigue at its worst, pain at its worst, physical functioning (PF), and global health status (GHS)/quality of life (QoL) for both sotorasib dose groups compared to the control group.
The 95% confidence intervals (CI) indicated improvements in pain at its worst and PF for both sotorasib dose groups and in GHS/QoL for the soto960+pmab group versus the control group. Hazard ratios for TTD < 1 suggested a trend towards delayed deterioration for patients treated in both sotorasib dose groups. Additionally, the 95% CI indicated delays in fatigue at its worst and PF for the soto240+pmab group.
The study concluded that both doses of sotorasib led to improved HRQoL and a trend towards decreased risk of deterioration compared to the control group in patients with chemorefractory mCRC. These findings further support the benefits of soto+pmab in this patient population.
The trial was sponsored by Amgen
Source: https://meetings.asco.org/abstracts-presentations/228863
Clinical Trial: https://clinicaltrials.gov/study/NCT05198934
Modest DP., Fakih M., Salvatore L., et al. (2024). “Health-related quality of life (HRQoL) in patients with metastatic colorectal cancer (mCRC) treated with sotorasib and panitumumab (pmab) versus trifluridine/tipiracil (T/T) or regorafenib (rego) in CodeBreaK 300.” Presented At ASCO- GI 2024 (Abstract 10).
