Fausto Petrelli1, Gianluca Perego2, Antonio Ghidini3, Michele Ghidini4, Karen Borgonovo5, Cinzia Scolari6, Renata Nozza6, Valentina Rampulla7, Antonio Costanzo7, Antonio Varricchio7, Emanuele Rausa8, Filippo Pietrantonio9, Alberto Zaniboni10. 1. Oncology Unit, Medical Sciences Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy. faupe@libero.it. 2. Pharmacy Unit, San Raffaele Hospital, Milan, Italy. 3. Oncology Unit, Casa di Cura Igea, Milan, Italy. 4. Oncology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 5. Oncology Unit, Medical Sciences Department, ASST Bergamo Ovest, Piazzale Ospedale 1, 24047, Treviglio, BG, Italy. 6. Pharmacy Unit, ASST Bergamo Ovest, Treviglio, BG, Italy. 7. Surgical Oncology Unit, ASST Bergamo Ovest, Treviglio, BG, Italy. 8. Surgery Unit, ASST Papa Giovanni XXIII, Bergamo, Italy. 9. Oncology Unit, Fondazione IRCCS Istituto Nazionale Tumori di Milano, Milan, Italy. 10. Oncology Unit, Fondazione Poliambulanza, Brescia, Italy.
Abstract
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.
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.
Entities:
Keywords:
Chemotherapy; Colorectal cancer; Refractory; Review; Third line
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