Sex-Based Heterogeneity in Response to Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis
| Autor: | Laura Pala, Emilia Cocorocchio, Filippo de Marinis, Vincenzo Bagnardi, Richard D. Gelber, Eleonora Pagan, Giuseppe Viale, Fabio Conforti, Aron Goldhirsch, Elisabetta Pennacchioli, Pier Francesco Ferrucci, Tommaso De Pas |
|---|---|
| Přispěvatelé: | Conforti, F, Pala, L, Bagnardi, V, Viale, G, De Pas, T, Pagan, E, Pennacchioli, E, Cocorocchio, E, Ferrucci, P, De Marinis, F, Gelber, R, Goldhirsch, A |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Lung Neoplasms medicine.medical_treatment Programmed Cell Death 1 Receptor B7-H1 Antigen Disease-Free Survival immune response law.invention chemotherapy regimen 03 medical and health sciences 0302 clinical medicine Randomized controlled trial law cytotoxic t-lymphocyte antigen 4 Internal medicine Humans Medicine CTLA-4 Antigen programmed cell death 1 ligand 1 Lung cancer 030304 developmental biology Sex Characteristics 0303 health sciences Chemotherapy business.industry Hazard ratio Editorials medicine.disease Chemotherapy regimen Confidence interval lung cancer Oncology 030220 oncology & carcinogenesis Meta-analysis non-small-cell lung carcinoma Female immunotherapy heterogeneity business Sex characteristics |
| Zdroj: | J Natl Cancer Inst |
| Popis: | BackgroundWe previously showed that therapy with anti–checkpoints T-lymphocyte-associated protein 4 (anti–CTLA-4) or antiprogrammed cell death protein 1 (anti–PD-1) agents was more effective for men as compared with women. However, because the sex-dimorphism of the immune system is complex, involving multiple elements of immune responses, it is possible that women could derive larger benefit than men from strategies other than therapy with immune checkpoint inhibitors (ICIs) alone. Here we investigated whether women could derive larger benefit than men from the combination of chemotherapy and anti-PD-1 or anti-PD-L1.MethodsWe performed two meta-analyses. The first included all randomized controlled trials (RCTs) testing anti-PD1 and anti–PD-L1 plus chemotherapy vs chemotherapy to assess different efficacy between men and women. The second included all RCTs of first-line systemic treatment in advanced non-small cell lung cancer testing anti–PD-1/PD-L1 given either alone or combined with chemotherapy to assess the different efficacy of these two immunotherapeutic strategies according to patients’ sex. For each RCT included in the two meta-analyses, first, a trial-specific ratio of hazard ratios (HRs) was calculated from the ratio of the reported hazard ratios in men and in women; second, these trial-specific ratios of hazard ratios were combined across trials using a random-effects model to obtain a pooled hazard ratios ratio. A pooled HRs ratio estimate lower than 1 indicates a greater treatment effect in men, and higher than 1 a greater effect in women.ResultsEight RCTs were included in the first meta-analysis. The pooled overall survival hazard ratios (OS-HRs) comparing anti–PD-1/PD-L1 plus chemotherapy vs chemotherapy was 0.76 (95% confidence interval [CI] = 0.66 to 0.87) for men and 0.48 (95% CI = 0.35 to 0.67) for women. The pooled ratio of the overall survival hazard ratios reported in men vs women was 1.56 (95% CI = 1.21 to 2.01), indicating a statistically significant greater effect for women. Six RCTs were included in the second meta-analysis: three tested an anti-PD-1 alone, whereas three RCTs tested anti-PD-1/PD-L1 plus chemotherapy. The pooled overall survival hazard ratios were 0.78 (95% CI = 0.60 to 1.00) in men and 0.97 (95% CI = 0.79 to 1.19) in women for anti–PD-1 alone, compared with 0.76 (95% CI = 0.64 to 0.91) in men and 0.44 (95% CI = 0.25 to 0.76) in women for anti–PD-1/PD-L1 plus chemotherapy. The pooled ratio of overall survival hazard ratios was 0.83 (95% CI = 0.65 to 1.06) for anti–PD-1 alone, indicating a greater effect in men, and 1.70 (95% CI = 1.16 to 2.49) for anti–PD-1/PD-L1 plus chemotherapy, indicating a greater effect in women.ConclusionWomen with advanced lung cancer derived a statistically significantly larger benefit from the addition of chemotherapy to anti–PD-1/PD-L1 as compared with men. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|