Second-Line Treatment Options in mCRC

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Outcomes can be dramatically impacted by the education a physician receives on optimal treatment strategies and side effect management, notes Axel Grothey, MD. Additionally, communication between the physician and patient makes a big difference, particularly in regard to side effect management, notes Al B. Benson III, MD. Future lines of therapy and drug holidays can be tailored, based on side effects or response to therapy.

For patients with metastatic colorectal cancer (mCRC), the ideal second-line therapy is generally tailored based on RAS status and frontline treatments, notes Tanios S. Bekaii-Saab, MD. For RAS wild-type patients, the biologic agents and chemotherapy backbone can be switched in the second-line setting.

The EGFR inhibitor panitumumab in combination with chemotherapy is FDA approved as an option for patients with mCRC, notes Bekaii-Saab. This therapy has demonstrated similar efficacy to cetuximab in clinical trials, suggesting the two agents are interchangeable.

In the phase III ASPECCT trial, cetuximab was compared with panitumumab in chemorefractory patients with KRAS wild-type mCRC, explains Grothey. The median overall survival was 10.4 months with panitumumab and 10.0 months with cetuximab (HR = 0.97; P = .0007). Median progression-free survival was 4.1 versus 4.4 months and overall response rate was 22% and 19.8% for panitumumab and cetuximab, respectively.

The level of skin toxicity was similar between the two arms in the ASPECCT trial, states Bekaii-Saab. Grade 3 or 4 skin toxicity occurred in 12.5% of patients with panitumumab versus 9.5% with cetuximab. Hypomagnesemia was more common with panitumumab (7.2% vs 2.6%) and infusion reactions were more common with cetuximab (1.8% vs 0.2%).

Given the similar efficacy and side effects with these agents, the next consideration would be costs, explains Alan P. Venook, MD. In the 80405 trial that explored bevacizumab versus cetuximab, there was a detailed cost-effectiveness and pharmacoeconomic analysis; however, in the beginning of the study oxaliplatin was still under patent, raising the price of the FOLFOX regimen. If one of the EGFR inhibitors was more favorably priced, treatment selection could be based on this parameter, Venook suggests.