New first-line immunotherapy-based combinations for metastatic renal cell carcinoma: a systematic review and network meta-analysis
A partir d'une revue systématique de la littérature publiée jusqu'en juin 2021 (6 essais incluant au total 5 478 patients et comparant 7 anticancéreux), cette méta-analyse compare l'efficacité, du point de vue de la survie globale, de la survie sans progression et du taux de réponse, et la toxicité de différentes combinaisons d'immunothérapies chez des patients atteints d'un carcinome à cellules rénales de stade métastatique
Several first-line immune-checkpoints inhibitors (ICI) based combinations have beenstudied in metastatic renal cell carcinoma (mRCC) without any direct comparison betweenthe regimens. The objective of this systematic review and network meta-analysis wasto provide the most updated evidence about the preferred first line ICI-based regimenfor mRCC. We searched various databases, including PubMed, Web of Science and Scopus and themajor conference proceedings (ASCO, ESMO). Eligible studies were randomized trial,published before June 2021 that evaluated first-line, ICI-based combinations comparedwith the standard of care in mRCC. Screening was performed independently by two investigators.A Cochrane risk-of-bias tool was used to assess trial quality. Relative effects ofcompeting treatments were assessed by Bayesian network meta-analysis. The PreferredReporting Items for Systematic Reviews and Meta-analyses guideline was used. Outcomesincluded overall survival (OS), progression-free survival (PFS), overall responserate, complete response and adverse events. Six trials with 5478 patients comparing 7 treatments were identified. Network meta-analysisshowed that lenvatinib plus pembrolizumab had the highest probability to be the besttreatment in terms of OS (surface under the cumulative ranking (SUCRA) 80.7%) andPFS (SUCRA 99.6%), while in sarcomatoid patients, nivolumab plus cabozantinib hadthe highest rank in terms of survival outcomes (SUCRA 85.8% and SUCRA 77.3%, respectively). Although we established a ranking among new first-line mRCC treatment combinations,the absence of direct comparisons between the multiple treatment options representsa major hurdle in establishing optimal therapeutic sequences. Our results could representa starting point for head-to-head trials between the most promising combinations.