In an analysis from the phase III CodeBreaK 300 study reported in The Lancet Oncology, Modest et al found that sotorasib and panitumumab were associated with better patient-reported outcomes (PROs) than standard of care (SOC) with trifluridine plus tipiracil or regorafenib in patients with KRAS G12C–mutant chemorefractory metastatic colorectal cancer.
Study Details
In the international open-label trial, 160 patients were randomly assigned between April 2022 and March 2023 to receive sotorasib at 960 mg plus panitumumab (n = 53), sotorasib at 240 mg plus panitumumab (n = 53), or investigator’s choice of SOC with trifluridine plus tipiracil or regorafenib (n = 54). The primary analysis of the trial showed a significant progression-free survival benefit with sotorasib at 960 mg plus panitumumab vs SOC. PROs evaluated included fatigue at its worst according to the Brief Fatigue Inventory, pain at its worst according to the Brief Pain Inventory, and Global Health Status–Quality of Life (GHS-QoL) and physical function subscales of the EORTC Quality of Life Questionnaire Core 30. Changes in PROs were evaluated at 9 weeks.
Key Findings
Least squares mean changes in PROs at week 9 favored the sotorasib plus panitumumab groups. Compared with the SOC group, differences in changes from baseline for the sotorasib 960 mg plus panitumumab group and the sotorasib 240 mg plus panitumumab group were: –0.89 (95% confidence interval [CI] = –1.80 to 0.01) and –0.58 (95% CI = –1.47 to 0.30) for fatigue at its worst; –1.45 (95% CI = –2.32 to –0.58) and –1.14 (95% CI = –2.00 to –0.28) for pain at its worst; 9.43 (95% CI = 2.31–16.56) and 6.49 (95% CI = –0.43 to 13.41) for GHS-QoL; and 5.38 (95% CI = –0.01 to 10.78) and 6.34 (95% CI = 1.07–11.62) for physical function.
Median times to deterioration for the sotorasib 960 mg plus panitumumab group, the sotorasib 240 mg plus panitumumab group, and the SOC group were: 16.09 weeks, not estimable, and 8.97 weeks for fatigue at its worst; 33.17 weeks, not estimable, and 12.24 weeks for pain at its worst; 19.93, 13.52, and 12.39 weeks for GHS-QoL; and not estimable, not estimable, and 9.54 weeks for physical function. Hazard ratios for the sotorasib plus panitumumab regimens vs SOC ranged from 0.54 to 0.95.
The investigators concluded: “Along with improved clinical outcomes, these analyses suggest that sotorasib plus panitumumab could represent a valuable new treatment in patients with KRAS G12C–mutated chemorefractory metastatic colorectal cancer.”
Dominik Paul Modest, MD, of the Department of Hematology, Oncology, and Cancer Immunology, Charite–Universitatsmedizin Berlin, Berlin, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Amgen. For full disclosures of all study authors, visit thelancet.com.
