Phase II study of third-line cetuximab rechallenge in patients with metastatic wild-type K-RAS colorectal cancer who achieved a clinical benefit in response to first-line cetuximab plus chemotherapy (JACCRO CC-08)

Background

Cetuximab rechallenge has been reported to be promising (Santini D et al. Ann Oncol 2012). We performed a multicenter phase II prospective study in Japan.

Methods

The study cohort comprised patients with metastatic wild-type K-RAS colorectal cancer who achieved a clinical benefit (confirmed stable disease for at least 6 months or clinical response) in response to first-line cetuximab 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 cetuximab (400 mg/m² as an initial dose followed by 250 mg/m² 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 36 patients were recruited. Two patients were excluded: one met the ineligibility criteria, and the other did not receive the study treatment because of poor condition at the time scheduled for treatment. The 3-month progression-free rate of 44.1% (95% confidence interval: 27.4-60.8) met the primary endpoint, with a median progression-free survival time of 2.4 months and an overall survival time of 8.1 months. The overall response rate and disease-control rate were 2.9% and 55.9%, respectively. The most frequent grade 3 to 4 adverse event was neutropenia (28.6%), and skin toxicities occurred in 80% of all patients, as expected.

Conclusions

Third-line cetuximab rechallenge may be clinically beneficial comparable to regorafenib and TAS102, with manageable toxicity.

Clinical trial identification

Trial protocol number: UMIN000010638 UMIN release date: 2013/5/7

Legal entity responsible for the study

Akihito Tsuji

Funding

Japan Clinical Cancer Research Organization

Disclosure

A. Tsuji: Horonaria : Merck Serono, Daiichi Sankyo. H. Hara: Horonaria : Merck Serono, Yakult Honsha Research Funding : Merck Serono, Daiichi Sankyo. M. Kotaka: Horonaria : Merck Serono, Yakult Honsha. W. Ichikawa: Consulting fees : Merck Serono, Daiichi Sankyo. All other authors have declared no conflicts of interest.