Second-Line Therapy for Metastatic CRC

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The second-line treatment armamentarium for patients with progressive metastatic colorectal cancer (mCRC) has expanded rapidly, with 3 VEGF-targeted therapies and 2 EGFR-targeted antibodies available in this setting. The VEGF-targeted therapies have demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) as second-line treatments for patients with mCRC.

EGFR inhibitors have demonstrated extensions in PFS; however, their OS benefit has remained largely confounded, due to crossover and other factors. A switch to expanded RAS testing could help further expand the OS benefit seen with EGFR inhibitors in the second-line setting.

Second-line treatment selection should be guided by mutational analysis and the rate of progression on frontline therapy, notes Axel Grothey, MD. If a patient progresses rapidly through their frontline therapy a complete switch may be required, from VEGF to EGFR or vise versa, depending on mutation status, or FOLFOX to FOLFIRI, Grothey suggests. In the 80405 study, second-line cetuximab was commonly used after first-line bevacizumab in the United States, notes Alan P. Venook, MD.

Data from the phase III RAISE trial demonstrated a 1.6-month OS advantage with ramucirumab plus FOLFIRI versus FOLFIRI alone as a second-line treatment for patients with mCRC, notes Herb Hurwitz, MD. In the study, the median OS was 13.3 months with ramucirumab plus chemotherapy versus 11.7 months with chemotherapy alone (HR = 0.84; P = .0219). Median PFS was 5.7 and 4.5 months, respectively (HR = 0.79; P = .0005).