Abstract
Background: Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer. Methods: The subgroup that received bevacizumab either prior to panitumumab or cetuximab monotherapy (ASPECCT) or in combination with irinotecan (WJOG6510G) was included. Multivariate Cox models were created, including the treatment arms as covariates together with patient, disease and treatment characteristics. Results: We included 185 and 189 patients in the panitumumab and cetuximab arms, respectively. The median overall survival was 12.8 and 10.1 months [p = 0.0031; log-rank test, stratified by trial; hazard ratio (HR), 0.72; 95% confidence interval (CI), 0.58–0.90], and the median progression-free survival was 4.7 and 4.1 months, in the panitumumab and cetuximab arms, respectively (p = 0.0207; HR, 0.79; 95% CI, 0.64–0.97). The treatment regimen was an independent prognostic factor of overall survival (adjusted HR, 0.69; 95% CI, 0.54–0.87; p = 0.0013). Conclusions: Panitumumab significantly prolonged the overall survival and progression-free survival, when compared with cetuximab in the cohort that previously received bevacizumab in the included studies. Clinical Trial Registration: ASPECCT trial registered with ClinicalTrials.gov (NCT01001377) and WJOG6510G trial registered with UMIN-CTR (UMIN000006643).
Highlights
Colorectal carcinoma (CRC) is the third leading type of cancer, and cause of cancer deaths, worldwide
We aimed to collect data for individual patients enrolled in each trial, to clarify whether panitumumab has better efficacy than cetuximab among patients who have previously received bevacizumab
374 patients were included in the efficacy analysis, and two were excluded from the safety analysis because they did not receive the study treatment
Summary
Colorectal carcinoma (CRC) is the third leading type of cancer, and cause of cancer deaths, worldwide. In the phase-III CO. study, cetuximab monotherapy improved overall survival (OS) and progression-free survival (PFS), versus best supportive care (BSC), in patients with wild-type KRAS exon 2 tumours [1,2]. No statistically significant benefit was seen with panitumumab monotherapy for OS in the 20020408 study This was probably because of patient crossover from BSC alone to BSC plus panitumumab after disease progression. The subsequent 20100007 phase-III study that lacked this crossover showed a clear improvement of OS with panitumumab plus BSC, versus BSC alone, in these patients with chemotherapy-refractory wild-type KRAS exon 2 mCRC. Phase-III ASPECCT and randomised phase-II WJOG6510G trials demonstrated the noninferiority of panitumumab, when compared with cetuximab, for overall survival in patients with chemotherapy-refractory wild-type KRAS exon 2 metastatic colorectal cancer
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