Efficacy of Second-Line Chemotherapy after a First-Line Triplet in Patients with Metastatic Colorectal Cancer

Background: Exposing patients with metastatic colorectal cancer (MCRC) to all three active chemotherapeutic agents (oxaliplatin, irinotecan, fluorouracil) has improved survival. The benefit of second-line chemotherapy after a first-line triplet is not clearly defined. We evaluated the efficacy of second-line chemotherapy in patients who had received first-line triplet therapy. Methods: The medical records of patients treated on a prospective trial of first-line triplet therapy were reviewed for second-line treatment. Univariate and multivariate analyses were performed to establish factors of prognostic significance. Results: Of the 53 patients who received first-line triplet therapy, 28 (53%) received second-line chemotherapy [13 men; 8 with a colon primary; mutant KRAS in 10, wild-type in 15, and unknown status in 3; Eastern Cooperative Oncology Group performance status (PS) of 1 in 16 patients, PS 2 in 3, PS 3 in 2, and unknown in 7; involved organs: liver in 17 patients, lung in 16, and peritoneum in 8]. Second-line chemotherapy consisted of XELOX or FOLFOX in 13 patients, XELIRI or FOLFIRI in 12, and single-agent irinotecan in 3. Concurrent bevacizumab was given in 16 patients (57%), and cetuximab, in 2 (7%). Median survival was 28.0 months [95% confidence interval (CI): 22.8 months to 33.2 months] for patients receiving second-line therapy and 23.0 months (95% CI: 13.2 months to 32.8 months) for those not receiving it. Best response was partial in 6 patients (21%), stable disease in 11 (39%), and progressive disease in 11 (39%). Median progression-free survival was 4.8 months (95% CI: 2.4 months to 9.6 months), and overall survival was 15 months (95% CI: 9.6 months to 20.4 months). Conclusions: Second-line chemotherapy after first-line triplet therapy in MCRC is feasible and suggests efficacy comparable to that reported for second-line therapy after a doublet, regardless of the agent used.