EGFR Targeting With Afatinib and Cetuximab Versus Cetuximab Alone in Chemorefractory Wild-type RAS Metastatic Colorectal Cancer: A Randomized Phase II Study With Circulating Tumor Cell Analysis.
TL;DR
The combination of afatinib and cetuximab was ineffective in treating chemorefractory wtRAS mCRC, and associated with high toxicity, and associated with high toxicity.
Abstract
Purpose
This phase II randomized trial evaluated the efficacy and safety of the combination of cetuximab and afatinib in chemorefractory metastatic colorectal cancer (mCRC).
Methods
We conducted a multicentre, open-label, randomized 2/1 noncomparative clinical trial in 75 patients with wild type (wt) RAS mCRC after chemotherapy failure. Patients (n = 51) received oral afatinib (40 mg/d) in combination with intravenous cetuximab (500 mg/m2 every 2 weeks) or cetuximab alone (n = 24) as an internal control arm. Crossover to afatinib was allowed after disease progression. The primary endpoint was the 6-month nonprogression rate with a minimal success rate of 30%. The prognostic value of circulating tumor cells (CTCs) was assessed in an ancillary analysis.
Results
In the combination arm, 9 patients (18%; 95% confidence interval [CI], 8-31), were progression-free at 6 months (primary endpoint not met). The objective response rate (ORR) was 26% (95% CI, 14-40). Median PFS and overall survival (OS) were 4.1 months (95% CI, 2.7-5.4) and 13.6 months (95% CI, 7.7-18.5) respectively. Thirty-seven patients (76%) in the combination arm and 16 patients (64%) in the control arm reported at least one severe (grade ≥ 3) toxicity. Two patients in the combination arm had grade 5 toxicity (sudden death and hypoglycemia). High baseline CTC levels and their decrease at day 14 were correlated to OS and ORR. CTC levels at day 14 were correlated to PFS.
Conclusion
The combination of afatinib and cetuximab was ineffective in treating chemorefractory wtRAS mCRC, and associated with high toxicity.