Roche's Tecentriq fails to increase survival in advanced bladder cancer study

Roche announced Wednesday that the Phase III IMvigor211 study of Tecentriq (atezolizumab) in people with locally advanced or metastatic urothelial cancer (mUC) whose disease progressed during or after treatment with a platinum-based chemotherapy failed to meet its primary endpoint of overall survival (OS) compared to chemotherapy. "These results are not what we had expected" remarked chief medical officer Sandra Horning.

Tecentriq gained FDA accelerated approval in May last year based on tumour response rate and duration of response data from the IMvigor210 study for the treatment of people with locally advanced or mUC who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based chemotherapy before surgery or after surgery. The IMvigor211 trial was designed to support full approval of the PD-L1 inhibitor globally and to serve as the confirmatory study to convert the accelerated clearance in the US to full approval.  

The IMvigor211 trial randomised 931 people with previously-treated mUC who progressed during or following a platinum-based regimen to receive either Tecentriq or chemotherapy. The trial's primary efficacy endpoint was OS, while key secondary goals include objective response rate, progression-free survival, duration of response and safety. 

According to Roche, the results seen in people treated with Tecentriq in IMvigor211 were generally consistent with those observed in a similar group of people in the IMvigor210 study. The company added that data from the Phase III trial will be examined in an effort to better understand the results, including "the initial observation that the chemotherapy arm results were better than study design assumptions." For further analysis, read ViewPoints: Roche throws an immuno-oncology curveball as the FDA is left to ponder what it does next.

Last month, the FDA granted accelerated approval to Tecentriq for the treatment of people with locally advanced or mUC who are not eligible for cisplatin chemotherapy. Roche noted the pivotal Phase III IMvigor130 study is currently ongoing in this population. For related analysis, see Physician Views Poll Results: Keytruda the biggest threat to Tecentriq in bladder cancer market, say oncologists.

"We believe that Tecentriq will continue to play an important role in the treatment for people with advanced bladder cancer, and will discuss these data with health authorities," a Roche spokesman said. The product, which is also approved in the US for use in certain patients with metastatic non-small-cell lung cancer, generated sales of 113 million Swiss francs ($112 million) in the first quarter, coming in ahead of analyst expectations of up to 111 million francs ($110 million).

Commenting on the news, Kepler Cheuvreux analyst David Evans said "this puts the existing US bladder cancer approval in serious doubt, and will also, of course, raise market concerns about Tecentriq's efficacy in other cancer types." Meanwhile, Deutsche Bank analysts suggested that the study failure placed up to $1 billion in peak sales at risk.

For related analysis, read ViewPoints: Roche throws an immuno-oncology curveball as the FDA is left to ponder what it does next.