Neoadjuvant immunotherapy for advanced, resectable non-small cell lung cancer: A systematic review and meta-analysis
A partir d'une revue systématique de la littérature (66 articles), cette méta-analyse évalue la toxicité et l'efficacité d'immunothérapies néoadjuvantes chez les patients atteints d'un cancer du poumon non à petites cellules, résécable et de stade avancé
Background : Neoadjuvant immunotherapy (nIT) is a rapidly emerging paradigm for advanced resectable non-small cell lung cancer (NSCLC). The objectives of this PRISMA/MOOSE/PICOD-guided systematic review and meta-analysis were (1) to assess the safety and efficacy of nIT, (2) to compare the safety and efficacy of neoadjuvant chemoimmunotherapy (nCIT) versus chemotherapy alone (nCT), and (3) to explore predictors of pathologic response with nIT and their association with outcomes. Methods : Eligibility was resectable stage I–III NSCLC and the receipt of programmed death-1/programmed cell death ligand-1 (PD-L1)/cytotoxic T-lymphocyte–associated antigen-4 inhibitors before resection; other forms and modalities of neoadjuvant and/or adjuvant therapies were allowed. For statistical analysis, the Mantel–Haenszel fixed-effect or random-effect model was used, depending on the heterogeneity (I2). Results : Sixty-six articles met the criteria (eight randomized studies, 39 prospective nonrandomized studies, and 19 retrospective studies). The pooled pathologic complete response (pCR) rate was 28.1%. The estimated grade
≥
3 toxicity rate was 18.0%. Compared with nCT, nCIT achieved higher rates of pCR (odds ratio [OR], 7.63; 95% confidence interval [CI], 4.49–12.97; p < .001), progression-free survival (PFS) (hazard ratio [HR] 0.51; 95% CI, 0.38–0.67; p < .001), and overall survival (OS) (HR, 0.51; 95% CI, 0.36–0.74; p = .0003) but yielded similar toxicity rates (OR, 1.01; 95% CI, 0.67–1.52; p = .97). The results remained robust on sensitivity analysis when all retrospective publications were removed. pCR was associated with improved PFS (HR, 0.25; 0.15–0.43; p < .001) and OS (HR, 0.26; 95% CI, 0.10–0.67; p = .005). PD-L1 expressors (
≥
1%) were more likely to achieve a pCR (OR, 2.93; 95% CI, 1.22–7.03; p = .02). Conclusions : In patients with advanced resectable NSCLC, neoadjuvant immunotherapy was safe and efficacious. nCIT improved pathologic response rates and PFS/OS over nCT, particularly in patients who had tumors that expressed PD-L1, without increasing toxicities.