PMID- 35119908 OWN - NLM STAT- MEDLINE DCOM- 20220429 LR - 20240214 IS - 1527-7755 (Electronic) IS - 0732-183X (Print) IS - 0732-183X (Linking) VI - 40 IP - 13 DP - 2022 May 1 TI - Sex Differences in Risk of Severe Adverse Events in Patients Receiving Immunotherapy, Targeted Therapy, or Chemotherapy in Cancer Clinical Trials. PG - 1474-1486 LID - 10.1200/JCO.21.02377 [doi] AB - PURPOSE: Women have more adverse events (AEs) from chemotherapy than men, but few studies have investigated sex differences in immune or targeted therapies. We examined AEs by sex across different treatment domains. METHODS: We analyzed treatment-related AEs by sex in SWOG phase II and III clinical trials conducted between 1980 and 2019, excluding sex-specific cancers. AE codes and grade were categorized using the Common Terminology Criteria for Adverse Events. Symptomatic AEs were defined as those aligned with the National Cancer Institute's Patient-Reported Outcome-Common Terminology Criteria for Adverse Events; laboratory-based or observable/measurable AEs were designated as objective (hematologic v nonhematologic). Multivariable logistic regression was used, adjusting for age, race, and disease prognosis. Thirteen symptomatic and 14 objective AE categories were examined. RESULTS: In total, N = 23,296 patients (women, 8,838 [37.9%]; men, 14,458 [62.1%]) from 202 trials experiencing 274,688 AEs were analyzed; 17,417 received chemotherapy, 2,319 received immunotherapy, and 3,560 received targeted therapy. Overall, 64.6% (n = 15,051) experienced one or more severe (grade >/= 3) AEs. Women had a 34% increased risk of severe AEs compared with men (odds ratio [OR] = 1.34; 95% CI, 1.27 to 1.42; P < .001), including a 49% increased risk among those receiving immunotherapy (OR = 1.49; 95% CI, 1.24 to 1.78; P < .001). Women experienced an increased risk of severe symptomatic AEs among all treatments, especially immunotherapy (OR = 1.66; 95% CI, 1.37 to 2.01; P < .001). Women receiving chemotherapy or immunotherapy experienced increased severe hematologic AE. No statistically significant sex differences in risk of nonhematologic AEs were found. CONCLUSION: The greater severity of both symptomatic AEs and hematologic AEs in women across multiple treatment modalities indicates that broad-based sex differences exist. This could be due to differences in AE reported, pharmacogenomics of drug metabolism/disposition, total dose received, and/or adherence to therapy. Particularly large sex differences were observed for patients receiving immunotherapy, suggesting that studying AEs from these agents is a priority. FAU - Unger, Joseph M AU - Unger JM AUID- ORCID: 0000-0002-5191-0317 AD - SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Vaidya, Riha AU - Vaidya R AUID- ORCID: 0000-0001-5316-6352 AD - SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Albain, Kathy S AU - Albain KS AUID- ORCID: 0000-0002-2899-2473 AD - Loyola University Chicago Stritch School of Medicine, Maywood, IL. FAU - LeBlanc, Michael AU - LeBlanc M AD - SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Research Center, Seattle, WA. FAU - Minasian, Lori M AU - Minasian LM AUID- ORCID: 0000-0002-0472-4079 AD - National Cancer Institute, Division of Cancer Prevention, Rockville, MD. FAU - Gotay, Carolyn C AU - Gotay CC AD - University of British Columbia, Vancouver, British Columbia, Canada. FAU - Henry, N Lynn AU - Henry NL AUID- ORCID: 0000-0002-4771-5930 AD - University of Michigan, Ann Arbor, MI. FAU - Fisch, Michael J AU - Fisch MJ AUID- ORCID: 0000-0001-5312-403X AD - AIM Specialty Health, Chicago, IL. FAU - Lee, Shing M AU - Lee SM AD - Columbia University, New York, NY. FAU - Blanke, Charles D AU - Blanke CD AD - SWOG Group Chair's Office/Knight Cancer Institute, Oregon Health & Science University, Portland, OR. FAU - Hershman, Dawn L AU - Hershman DL AUID- ORCID: 0000-0001-8807-153X AD - Columbia University, New York, NY. LA - eng GR - U10 CA180819/CA/NCI NIH HHS/United States GR - U10 CA180888/CA/NCI NIH HHS/United States GR - UG1 CA189974/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220204 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Immunologic Factors) SB - IM CIN - Eur J Clin Pharmacol. 2022 Aug;78(8):1355-1356. PMID: 35562621 MH - Clinical Trials as Topic MH - Female MH - Humans MH - Immunologic Factors/therapeutic use MH - Immunotherapy/adverse effects MH - Male MH - *Neoplasms/drug therapy/etiology MH - Patient Reported Outcome Measures MH - *Sex Characteristics PMC - PMC9061143 COIS- Kathy S. AlbainHonoraria: Encore Medical EducationResearch Funding: Seattle Genetics (Inst), Quantum Leap Healthcare Collaborative (Inst)Other Relationship: Seattle Genetics Michael LeBlancConsulting or Advisory Role: Agios Carolyn C. GotayStock and Other Ownership Interests: Johnson & Johnson/Janssen N. Lynn HenryResearch Funding: Blue Note Therapeutics (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/27894/summary Michael J. FischEmployment: AIM Specialty HealthStock and Other Ownership Interests: AnthemPatents, Royalties, Other Intellectual Property: Healthcore, Inc, A subsidiary of Anthem, IncOpen Payments Link: https://openpaymentsdata.cms.gov/physician/767578 Shing M. LeeConsulting or Advisory Role: PTC TherapeuticsResearch Funding: Merck, Genentech/Roche Dawn L. HershmanConsulting or Advisory Role: AIM Specialty HealthNo other potential conflicts of interest were reported. EDAT- 2022/02/05 06:00 MHDA- 2022/04/30 06:00 PMCR- 2022/02/04 CRDT- 2022/02/04 17:10 PHST- 2022/02/05 06:00 [pubmed] PHST- 2022/04/30 06:00 [medline] PHST- 2022/02/04 17:10 [entrez] PHST- 2022/02/04 00:00 [pmc-release] AID - JCO.21.02377 [pii] AID - 10.1200/JCO.21.02377 [doi] PST - ppublish SO - J Clin Oncol. 2022 May 1;40(13):1474-1486. doi: 10.1200/JCO.21.02377. Epub 2022 Feb 4.