Episode 4: The CheckMate 901 trial
Presented by Prof Emmanuel Seront (UCL Louvain) and Prof Christof Vulsteke (Maria Middelares Gent)
Prof Vulsteke from Maria Middelares Gent will present the CheckMate901 study, presented at ESMO2023. In this trial, SOC cisplatin chemotherapy was combined with nivolumab for the first-line treatment of metastatic urothelial cell cancer. CheckMate901 marked the first positive trial in this setting.
Notably, cis-eligible patients were included in this trial and these patients demonstrated clear improvements in OS and PFS. While the statistical gain from 18 months to 21 months in OS is significant, it is essential to acknowledge that 18 months already represents a relatively high duration for the control arm. The difference in PFS was marginal initially and became more pronounced later. The number of complete responders doubled to 21 per cent, with a median duration of response exceeding 30 months in these patients, suggesting that a durable response can be achieved with this therapy.
This trial represents the first evidence of the benefit of adding checkpoint inhibition to chemotherapy. Despite the consensus among experts regarding the favourable outcomes, there is scepticism regarding whether there is a substantial difference between using chemotherapy with nivolumab, pembrolizumab, or atezolizumab. The success observed in CheckMate901 can be ascribed to the careful selection of cis-eligible patients for the trial. Subgroup analyses with atezolizumab and pembrolizumab showed similar benefits in this population.
Professor Vulsteke recently presented the results of enfortumab vedotin plus pembrolizumab (EV+Pembro), a winning combination but not yet available. The approval of EV+Pembro for first-line treatment is awaited as no apparent contraindications obstruct its use in any patient. Upon its availability, it is anticipated to become the favoured option.
Currently, clinicians are left with the decision between the JAVELIN regimen and cisplatin with nivolumab for their next patient with metastatic urothelial cancer. At present, the JAVELIN regimen emerges as the optimal choice, as reimbursement for the addition of nivolumab in the first line is pending. If reimbursement becomes available, it would certainly be given to cis-eligible patients.
Meanwhile, patients may be encouraged to enrol in forthcoming biomarker-driven clinical trials. These trials explore drug conjugates with checkpoint inhibitors, such as disitamab vedotin in HER2+ patients or the trial involving ‘bicycle’ attached to MMAE chemotherapy. The control arm in these randomized trials may evolve, presently comprising chemotherapy followed by avelumab in stable disease.
Nonetheless, for future clinical trials, EV+Pembro would likely serve as the preferred control arm, as both experts agree that it would be unethical to deny this treatment after the results of the EV-302 trial.
References:
van der Heijden, M.S. et al.(2023) Nivolumab plus gemcitabine-cisplatin versus gemcitabine-cisplatin alone for previously untreated unresectable or metastatic urothelial carcinoma: Results from the phase III CheckMate 901 trial. Annals of Oncology, Volume 34(S2): S13415.