Why did Atezolizumab fail in advanced Urothelial Bladder Cancer?
Florence, Italy: Today at the EACR-AACR-SIC Conference on “The Challenges of Optimizing Immuno and Targeted Therapies,” Tom Powles MRCP MD, Clinical Professor of Geniturinary Oncology at Barts Cancer Institute in London, gave a special lecture on the IMvigor211 trial (NCT02302807).
This was a phase 3 study of the PD-L1 checkpoint inhibitor atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer.
Prof Tom Powles (Barts Cancer Institute)
Readers may recall we interviewed Prof Powles back in August 2015 about the potential for the PD-L1 checkpoint inhibitor atezolizumab in urothelial bladder cancer? (See post: Atezolizumab PD-L1 Checkpoint Inhibitor will Change Bladder Cancer Treatment.)
We also featured the atezo data presented by Dr Jonathan Rosenberg (MSKCC) at ESMO 2015 on Episode 7 of the Novel Targets Podcast, where we also heard Prof Powles tell us about the long durable responses he had obtained in clinical practice in some of his patients.
Subsequently on May 18, 2016 the US Food and Drug administration (FDA) granted accelerated approval to atezolizumab (Tecentriq) for urothelial bladder cancer (link to news release).
Fast forward a year to May 9, 2017 and the surprise announcement that the confirmatory phase 3 trial (IMvigor211) failed to meet its primary endpoint (link to Genentech press release).
So what happened? Why did the atezo phase 3 trial end up being negative when we saw durable responses in the randomised phase 2 trial and other PD-1 checkpoint inhibitors have shown an overall survival benefit in the same indication?
Many in the media only want to write about positive data, but in science we often learn as much from our failures as we do from our successes, perhaps even more sometimes.
IMvigor211 was expected to be a positive trial especially after the recent Merck success gaining an overall survival benefit for pembrolizumab, so the negative result is noteworthy and one that anyone in the field of cancer immunotherapy drug development will want to understand.
Professor Powles kindly spoke to BSB and shared his perspective.
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