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Fischer, Laura E. ORCID logoORCID: https://orcid.org/0000-0001-8752-5827; Stintzing, Sebastian; Weikersthal, Ludwig Fischer von; Modest, Dominik P.; Decker, Thomas; Kiani, Alexander ORCID logoORCID: https://orcid.org/0000-0002-2494-4087; Kaiser, Florian; Al-Batran, Salah-Eddin; Heintges, Tobias; Lerchenmüller, Christian; Kahl, Christoph; Seipelt, Gernot; Kullmann, Frank; Stauch, Martina; Scheithauer, Werner; Giessen-Jung, Clemens; Uhlig, Jens; Peuser, Bettina; Denzlinger, Claudio; Stahler, Arndt; Weiss, Lena; Heinrich, Kathrin; Held, Swantje; Jung, Andreas; Kirchner, Thomas and Heinemann, Volker (2022): Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3. In: British Journal of Cancer, Vol. 127, No. 5: pp. 836-843 [PDF, 788kB]


Background The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients' age and sidedness of primary tumour. Methods The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (>= 65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher ' s exact test, OS and PFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS. Results Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29;P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%;P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%;P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86;P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (>= 65 years: 16.6 months vs 23.6 months, HR 1.1;P = 0.87;P = 0.31). Conclusions In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC.

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