Phase II study of third-line panitumumab rechallenge in patients with metastatic wild-type KRAS colorectal cancer who achieved a clinical benefit in response to first-line panitumumab plus chemotherapy

Abstract

Introduction: Cetuximab rechallenge has been reported to be promising (Santini D et al. Ann Oncol 2012 and Tsuji A et al. Annals of Oncology, Volume 27, Issue suppl_6, 2016, 510P,).On the other hand, usefulness of panitumumab for cetuximab is expected (WJOG6510G, ASCO-GI 2017). We performed a multicenter phase II prospective study panitumumab rechallenge in Japan. Methods: The study cohort comprised patients with metastatic wild-type KRAS color- ectal cancer who achieved a clinical benefit (confirmed stable disease for at least 6 months or clinical response) in response to first-line panitumumab plus chemotherapy, then had disease progression and received second-line chemotherapy, and finally had a clear new progression of disease. Patients received bi-weekly irinotecan (150 mg/ m2) combined with panitumumab (8 mg/m2 bi-weekly). The primary endpoint was the 3-month progression-free rate. The required sample size was estimated to be at least 30 patients, assuming a 3-month progression-free rate of less than 15% as the null hypothesis versus a 3-month progression-free rate of higher than 35% as the alternative hypothesis, a power of 80%, and an alpha value of 0.05. Results: A total of 25 patients were recruited. One patients were excluded: one did not receive the study treatment because of poor condition at the time scheduled for treatment. 22 of 25 patients received bevacizumab combined therapy before this trial. The 3-month progression-free rate of 54.2% (95% confidence interval: 34.2-74.1) met the primary end- point, with a median progression-free survival time of 3.8months and an overall survival time of 8.9 months. The overall response rate and disease-control rate were 8.3% and 50.0%, respectively. The most frequent grade 3 to 4 adverse event was neutropenia (8.3%), and skin toxicities (all grade) occurred in 91.7% of all patients, as expected. Conclusion: Third-line panitumumab rechallenge may be clinically beneficial treatment before regorafenib and TAS102, with manageable toxicity. Clinical trial identification: Trial protocol number: UMINUMIN000011440, UMIN release date: 2018/01/17.