Chemoimmunotherapy in urothelial cancer: concurrent or sequential?
Menés respectivement dans 21 et 14 pays sur 1 010 patients atteints d'un carcinome urothélial de stade avancé et sur 334 patients atteints d'un cancer de la vessie sans envahissement musculaire, à haut risque de récidive et ne répondant pas à une injection intravésicale de BCG, ces deux essais évaluent l'efficacité et la toxicité du pembrolizumab, seul ou combiné avec une chimiothérapie
In The Lancet Oncology, Thomas Powles and colleagues report the primary data from the phase 3 KEYNOTE-361trial, in which patients with locally advanced, unresectable, or metastatic urothelial cancerwere randomly assigned to receive chemotherapy, pembrolizumab, or a combination ofthese. The authors should be commended on the excellent study design, trial conduct,and data reporting. This trial adds to an existing array of influential frontlinetrials in advanced urothelial carcinoma, bearing relevant resemblance to IMvigor130,which used a similar study design but substituted the PD-1 inhibitor pembrolizumabfor the PD-L1 inhibitor atezolizumab; another difference was the use of placebo withchemotherapy in IMvigor130. Neither study led to a significant overall survival improvement with concurrent chemoimmunotherapyversus chemotherapy alone. Although the KEYNOTE-361 trial also showed no differencein progression-free survival between the treatment groups, IMvigor130 did report asignificant improvement in progression-free survival with chemoimmunotherapy versuschemotherapy (median 8·2 vs 6·3 months; HR 0·82, 95% CI 0·70–0·96), but the difference was modest, of dubiousclinical significance, and did not lead to a change in clinical practice. Potential reasons for the slight discrepancy in results between the two studies includedifferences in baseline patient characteristics, statistical design nuances, follow-uptime, number of events, the proportion of patients in the chemotherapy control groupwho received subsequent anti-PD-(L)1 therapies (which can affect overall survival,and was higher in the KEYNOTE-361 study [48%] than in IMvigor130 [20%]), other subsequenttherapies, and unmeasured confounders.
The Lancet Oncology , commentaire, 2020