Approved Bladder Cancer Drug Fails to Improve Survival in Confirmatory Trial

An interim analysis of the phase III IMvigor211 study found that atezolizumab, a PD-L1 inhibitor, did not meet its primary endpoint of improving overall survival compared with chemotherapy in patients with locally advanced or metastatic urothelial cancer who had received at least one prior line of platinum-containing chemotherapy, according to the drug’s developer, Roche.

Sandra Horning, MD, the chief medical officer and head of global product development at Roche, said in a press release that “these results are not what we expected.” She added that they still expect atezolizumab (Tecentriq) to play an important role in the treatment of patients with this malignancy.

The US Food and Drug Administration (FDA) initially announced its accelerated approval of atezolizumab for bladder cancer in May 2016, for the treatment of patients who had already received platinum-based chemotherapy based on results of the phase II, open-label, single-arm IMvigor210 trial; the accelerated approval was contingent on positive results in this phase III trial.

According to Roche, the phase III IMvigor211 trial comparing atezolizumab with chemotherapy directly failed to show improvement with the immunotherapy agent. The trial enrolled 931 patients with previously treated metastatic urothelial carcinoma who had progressed during or following a platinum-based regimen. It compared atezolizumab with vinflunine, paclitaxel, or docetaxel chemotherapy. Overall survival, the primary endpoint, will be tested in successive fashion in subgroups based on PD-L1 expression, with highest levels of expression tested first.

The results with atezolizumab were “generally consistent” with those observed in the single-arm IMvigor210 trial; that trial did not involve a chemotherapy comparator.

Last month atezolizumab was granted an expanded, accelerated approval by the FDA for use as initial therapy in patients with urothelial carcinoma who are not eligible for cisplatin chemotherapy. This expanded approval was also based on results of the IMvigor210 trial. In cohort 1 of that trial, 119 patients who were ineligible for cisplatin-containing chemotherapy had an overall response rate to atezolizumab of 23.5%, with 6.7% achieving a complete response.

The interim analysis of IMvigor211 also found a similar safety profile for atezolizumab as seen in the phase II trial. In that cohort, the most common grade 3/4 adverse events (AEs) included fatigue (8% of patients), urinary tract infection (5%), anemia (7%), and diarrhea (5%). The study drug was discontinued due to AEs in five patients (4.2%) in the phase II trial.