Aristotelis Bamias, MD, discusses key efficacy data from a final analysis of the phase 3 IMvigor130 trial in metastatic urothelial carcinoma.
Aristotelis Bamias, MD, associate professor of medicine, Medical School, University of Athens in Greece, discusses key efficacy data from a final analysis of the phase 3 IMvigor130 trial (NCT02807636) in metastatic urothelial carcinoma (mUC).
The IMvigor130 study investigated the potential role of atezolizumab (Tecentriq) alone or in combination with chemotherapy in the first-line treatment of patients with mUC. Patients in arm A received atezolizumab plus chemotherapy, arm B received atezolizumab monotherapy, and arm C received platinum-based chemotherapy alone. Exploratory analyses of the trial were conducted between arms B and C, revealing that atezolizumab monotherapy showed a signal of benefit and favorable toxicity compared with placebo plus platinum chemotherapy in patients with high PD-L1 expression. Although the trial did meet its first primary end point of prolonged progression-free survival (PFS), it failed to meet its co-primary end point of overall survival (OS) between arms A and C.
Accordingly, an exploratory analysis of the benefit-risk ratio in arms B and C were conducted in the intention-to-treat (ITT) population and PD-L1–high population. Ultimately, final OS analysis confirmed previous findings. No significant difference in OS was observed between arms B and C, with a median OS of 15.2 months vs 13.3 months, respectively. Additionally, evaluation of patients according to PD-L1 expression level showed no difference in outcomes in the population with no or low PD-L1 expression. However, there was a numerical prolongation of OS observed in patients with high PD-L1 expression in arm B vs arm C. Particular focus was also placed on a subgroup analysis of cisplatin-ineligible patients with mUC, as these patients lack effective first-line therapies. The prolongation of OS previously observed was found to be more pronounced in cisplatin-ineligible patients. No new safety concerns were observed with this study, and atezolizumab was found to be more tolerable than chemotherapy.
Despite observing a trend towards improved OS, this result was not statistically significant according to the trial parameters. Accordingly, this study was deemed negative. These results in combination with other trials in mUC indicate that the efficacy of immunotherapy is not significantly improved with the addition of concurrent chemotherapy. Moreover, it is important to interpret these results in comparison with the current standard of care in mUC, which is chemotherapy followed by avelomab (Bavencio) maintenance.
Overall, these results support the current European indication for atezolizumab in the first-line treatment of mUC. Notably, this indication has recently been withdrawn in the United States. However, these data indicate that atezolizumab monotherapy may be considered as a first-line option for cisplatin-ineligible patients with high PD-L1–expressing mUC.
Editor’s Note: Dr Bamias disclosed honoraria from Astellas Pharma; Bristol-Myers Squibb; Debiopharm Group; MSD; Sanofi; consulting or advisory role for AstraZeneca; Bristol-Myers Squibb; Ferring; Ipsen; MSD; Pfizer; Roche; and research funding from AstraZeneca (Inst); Bristol-Myers Squibb (Inst); Ipsen (Inst); Pfizer (Inst); Roche (Inst)