ASCO 2019 - Enfortumab comes out fighting in bladder cancer

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At ASCO 2019, results were presented from the phase II EV-201 trial, which evaluated antibody drug conjugate (ADC) enfortumab vedotin in relapsed patients with locally advanced or metastatic bladder cancer. The data presented were from Cohort 1 of the trial, which evaluated enfortumab in relapsed patients who had been treated with a platinum and a checkpoint inhibitor. Kantar's Len Kusdra reviews the study in the video below. [video mp4=""][/video] In this study, the overall response rate in 125 treated patients was 44%.  Twelve percent had a complete response and 32% had a partial response. Responses were similar in all subgroups analysed. The median duration of response was 7.6 months, the median PFS was 5.8 months and median OS was 11.7 months. The toxicity profile was very favourable with the most common Grade 3 or greater adverse events being rash (12%), neutropenia (8%), anemia (7%), fatigue (6%), and hyperglycemia (6%). The discontinuation rate due to adverse events was 12%, of which peripheral neuropathy was the most common adverse event that led to discontinuation. Overall, the data looks very promising and compares favourably, and in some cases exceeds, that seen with checkpoint inhibitors used in the relapse setting. The results here will most likely support accelerated approval and indeed, regulatory filing is planned for enfortumab later this year. Additional targeted agents are also making entry into the relapsed space and will increase the competition beyond the checkpoint inhibitors. Sacituzumab govitecan is another TROP2-targeted ADC and it is being evaluated in a pivotal Phase II trial in the same setting. Recent data presented at ASCO GU showed sacituzumab to have promising activity in patients.  In addition, Balversa was recently approved in patients who are positive for FGFR2,3 mutations. The entry of multiple targeted agents in this space will certainly provide challenges for physicians, with issues being centered around how best to sequence these agents through multiple lines of therapy; the optimal treatment strategy for patients who are positive for a biomarker, such as FGFR, will also weigh into physicians’ treatment decisions. Favouring enfortumab is its evaluation in patients after treatment with a checkpoint inhibitor, an area that has generally seen little development since the onset of the checkpoint inhibitor era. Enfortumab is positioned nicely to address that unmet need and, if approved, will be first to market in this setting. Overall, enfortumab represents an important step forward in the management of relapsed bladder cancer and provides hope for patients with this deadly disease. Click here to view exclusive live coverage from ASCO 2019.