A systematic review of salvage therapies in refractory metastatic colorectal cancer

Purpose Established that the only approved agents in previously treated metastatic colorectal cancer (CRC) are trifluoridine/tipiracil and regorafenib, we conducted a systematic review of all the published phase 2–3 trials, with the scope to evaluate the benefit of any later-line regimens in refractory metastatic CRC. Methods Phase 2–3 studies that enrolled patients with stage IV disease receiving salvage therapies for refractory CRC were identified using electronic databases (Pubmed, EMBASE, and Cochrane Library). Clinical outcomes were pooled using a point estimates for the weighted values of median overall survival (OS), progression-free survival (PFS), response rate (ORR), stable disease rate (SD), and 6-month and 1-year OS. Results Overall, 7556 patients were included from 67 studies ( n = 70 arms). Overall, the pooled ORR and SD were 15.4% (95% CI 13–18%) and 36.9% (95% CI 33.5–40.6%). Median PFS, 6-month and 1-year OS, and median OS were 3.2 (95% CI 2.9–3.3) months, 65.4% (95% CI 61.9–68.8%), 36% (95% CI 32.3–39.9%) and 8.8 (95% CI 8.3–9.2) months. Overall survival was different in the monochemotherapy, polychemotherapy, chemotherapy + targeted therapy, and targeted therapy alone arms (7.6, 9.5, 10.3, and 7.9 months, respectively, P for difference = 0.01). Median PFS were respectively 2.3, 3.9, 3.8, and 2.6, respectively ( P for difference < 0.01). Conclusions Overall, combination therapy (polychemotherapy with or without targeted agents) is associated with a higher control of disease and better outcome than approved agents. Treatment, if possible, should be personalized according to the patients’ conditions, physician preference and molecular profile of disease.