Journal article
Sex differences in efficacy and toxicity of first-line treatment of metastatic colorectal cancer (CRC): An analysis of 18,399 patients in the ARCAD database.
- Wagner, Anna Dorothea Lausanne University Hospital, Lausanne, Switzerland;
- Rakez, Manel Fondation A.R.CA.D-Aide et Recherche en CAncérologie Digestive, Levallois-Perret, France;
- Chibaudel, Benoist GERCOR, Paris, France;
- Adams, Richard Velindre Cancer Centre, Cardiff, United Kingdom;
- Zalcberg, John Raymond Peter MacCallum Cancer Centre, Melbourne, Australia;
- Saltz, Leonard B. Department of Colorectal Oncology, Memorial Sloan Kettering Cancer Center, New York, NY;
- Venook, Alan P. University of California San Francisco, San Francisco, CA;
- Schmoll, Hans-Joachim Martin Luther University, Halle, Germany;
- Douillard, Jean-Yves Institut de Cancérologie de l'Ouest-René Gauducheau, Nantes, France;
- Tournigand, Christophe Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, Créteil, France;
- Heinemann, Volker University Hospital Munich, LMU Munich, Munich, Germany;
- Goldberg, Richard M. West Virginia University Cancer Institute, Morgantown, WV;
- Hecht, J. Randolph David Geffen School of Medicine, University of California, Los Angeles, CA;
- Cremolini, Chiara Department of Translational Research and New Technologies in Medicine and Surgery, Unit of Medical Oncology 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy;
- Diaz-Rubio, Eduardo Hospital Clínico Universitario San Carlos, Madrid, Spain;
- Grothey, Axel West Cancer Center, Germantown, TN;
- Shi, Qian Mayo Clinic, Rochester, MN;
- De Gramont, Aimery Franco-British Institute, Levallois-Perret, France;
Published in:
- Journal of Clinical Oncology. - American Society of Clinical Oncology (ASCO). - 2020, vol. 38, no. 15_suppl, p. 4029-4029
English
4029 Background: The clearance of 5-FU differs significantly between men (M) and women (W). Adjuvant chemotherapy (CT) for CRC has a higher toxicity in W. The impact of sex on efficacy and toxicity in first-line trials of metastatic CRC (mCRC) is unknown. Methods: We analyzed patient (pt) and tumor characteristics, toxicities (nausea (AE1), vomiting (AE2), diarrhea, neutropenia (AE3)) and efficacy (overall survival (OS), progression-free survival (PFS)) according to sex in the following treatment groups: A: CT alone, B: CT + bevacizumab, C: CT + EGFR-antibodies, with subgroup analyses in the CT alone group for single-agent, doublets and triplets, as well as irinotecan- and oxaliplatin-based regimens. Pts from trials with treatments still used today and all relevant data available were eligible. OS and PFS were assessed using Kaplan-Meier and Cox models adjusted for primary tumor location and performance status (PS). Results: We included 28 trials with 18.399 pts (11.352 M and 7.047 W). W were younger (61 vs. 63 years), had more often a PS of 1 (49 vs 45%), BRAF mutations (10 vs. 7%), right-sided tumors (42 vs. 35%) and less often rectal tumors (26 vs. 32%). Significant differences in toxicity are reported in table. Rates of diarrhea were similar. There was no sex disparity in OS in the predefined subgroups except for pts receiving triplets where OS was better in M (HRadj =1.39 (1.05 - 1.85)). Median (interquartile range) OS in months for M and W was 16.7 (9.2-27.4) and 16.2 (8.9-27.2) in group 1, 21.9 (12.7-37.5) and 22.3 (12.9 – 39.0) in group 2, and 26.8 (14.6-45.3) and 24.8 (12.3-49.2) in group 3. HRsadj (W vs M) (95% CI), p values for OS were 1.02 (0.96-1.09), .557, 0.92 (0.83-1.03), .142, 0.99 (0.85-1.14), .866. Conclusions: M and W with mCRC differ significantly regarding patient and tumor characteristics. The significant higher toxicity in W does not translate in a higher treatment efficacy. Apart from known sex differences in pharmacokinetics of 5-FU, differences in pharmacodynamics must be postulated. [Table: see text]
- Language
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- English
- Open access status
- closed
- Identifiers
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- DOI 10.1200/jco.2020.38.15_suppl.4029
- ISSN 0732-183X
- Persistent URL
- https://sonar.ch/global/documents/29831
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