Modulation of chemoimmunotherapy efficacy in non-small cell lung cancer by sex and histology: a real-world, patient-level analysis

• Published in: BMC cancer Vol. 22; no. 1; pp. 80 - 8
• Main Authors: Tuminello, Stephanie, Alpert, Naomi, Veluswamy, Rajwanth R., Kumar, Arvind, Gomez, Jorge E., Flores, Raja, Taioli, Emanuela
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.01.2022; BioMed Central Ltd; BMC
• Subjects: Aged; Biomedical and Life Sciences; Biomedicine; Cancer; Cancer Research; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Care and treatment; Chemotherapy; Clinical trials; Comorbidity; Databases, Factual; Demographic aspects; Diagnosis; Family income; Female; Females; Health Promotion and Disease Prevention; Histology; Humans; Immune checkpoint inhibitors; Immunotherapy; Immunotherapy - mortality; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Male; Males; Medicine/Public Health; Middle Aged; Non-small cell lung carcinoma; NSCLC; Oncology; Patients; Propensity Score; Proportional Hazards Models; Radiation; Risk Factors; Sex Factors; Small cell lung carcinoma; Squamous cell carcinoma; Statistical analysis; Surgical Oncology; Survival Analysis; Survival Rate; Testing; Treatment Outcome; Variables; United States; Squamous cell carcinoma; Immune checkpoint inhibitors; NSCLC; Immunotherapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-022-09187-y

Background It has been postulated that patient’s sex impacts response to immunotherapy. Sex modulation of immunotherapy benefit, however, has not yet been explored using patient-level data, where potential confounders, as well as histologic type, can be accounted for. Here we investigated the association between sex and chemoimmunotherapy efficacy for non-small cell lung cancer (NSCLC) using a large, nation-wide dataset. Patients & methods Stage IV NSCLC patients diagnosed in 2015 were identified in the National Cancer Database (NCDB). Patients were treated with either chemoimmunotherapy or chemotherapy alone. The efficacy of the addition of immunotherapy treatment by sex was investigated using both an adjusted Cox proportional hazards model and propensity-score matching, in both the overall cohort and stratified by histological subtype. Results 2064 (16%) patients received chemoimmunotherapy and10,733 (84%) received chemotherapy alone. Adjusted survival analysis in the overall cohort showed that both males (hazards ratio (HR) adj : 0.80, 95% CI: 0.74–0.87) and females (HR adj : 0.83, 95% CI: 0.76–0.90) had better OS when treated with chemoimmunotherapy than chemotherapy alone, with no statistically significant interaction between sex and receipt of immunotherapy ( p  = 0.63). Propensity matching confirmed these results. However, for those with squamous cell histology, male patients derived more benefit from chemoimmunotherapy treatment than females (HR adj : 0.73, 95% CI: 0.58–0.91 vs HR adj : 1.03, 95% CI: 0.76–1.38; p for interaction = 0.07). Conclusion Male patients with squamous cell carcinoma may derive more benefit from chemoimmunotherapy treatment. Histology likely plays an important role in how sex modulates immunotherapy efficacy.