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After accelerated approval, both drugs fall short of overall survival endpoint. They will stay on the market for other indications.
Drugmarkers have recently withdraw urothelial cancer indications from two important cancer medications.
Roche announced in early March that it had voluntarily withdrawn the Tecentriq’s (atezolizumab) indication as a treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) previously treated with platinum-based chemotherapy.
Two weeks earlier, AstraZeneca announced that it was withdrawing the use of its checkpoint inhibitor Imfinzi (durvalumab) as a treatment for bladder cancer in the United States following a failure to meet endpoints in a post-approval clinical study.
“The Accelerated Approval Program allows people with difficult-to-treat cancers to receive certain new therapies earlier,” Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, said in a press release. “While the withdrawal of Tecentriq for prior-platinum treated bladder cancer is disappointing, Tecentriq continues to demonstrate benefits across multiple cancer types and therefore remains a meaningful treatment option for many patients.”
The FDA initially granted accelerated approval for the indication for Tecentriq in 2016 for patients who have disease progression during or following platinum-based chemotherapy, or whose disease has worsened within 12 months of receiving platinum-based neoadjuvant or adjuvant chemotherapy.2
Accelerated approval was based on results of the phase 2 IMvigor210 trial, which showed promising responses in patients receiving second-line Tecentriq versus historical controls.
But continued approval of the indication was contingent upon the results of the phase 3 IMvigor211 trial, which failed to meet its primary end point of overall survival improvement in patients with tumors that express PD-L.
AstraZeneca announced in February the voluntary withdrawal of Imfinzi indication in the U.S. for previously treated adult patients with locally advanced or metastatic bladder cancer. The withdrawal does not affect the indication for non-small cell lung cancer.
The statement from Dave Fredrickson, executive vice president, oncology business unit of AstraZeneca, in a press release was not dissimilar from what Roche’s Garrraway had said. “While the withdrawal in previously treated metastatic bladder cancer is disappointing, we respect the principles FDA set out when the accelerated approval pathway was founded and remain committed to bringing new and innovative options to patients,” said Fredrickson via a press release.
Imfinzi, an immunotherapy, was granted accelerated approval in May 2017 based on positive results from Study 1108, a phase I/II trial.However, continued approval was dependent on results from the DANUBE phase 3 trial, which did not meet its primary endpoints as seen in The Lancet Oncology.
The FDA’s Accelerated Approval Program enables earlier approval for medications treating serious conditions that fill an unmet medical need, and companies are required to continue studying whether the treatment offers clinical benefit in phase 4 confirmatory trials.
Imfinzi as monotherapy or in combination with tremelimumab was evaluated for survival outcomes in the DANUBE phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma across 23 countries.
Patients were randomized to receive Imfinzi monotherapy (1500 mg) administered intravenously (IV) every 4 weeks; durvalumab (1500 mg) plus tremelimumab (75 mg) administered by IV every 4 weeks for up to 4 doses, followed by Imfinzi maintenance (1500 mg) every 4 weeks; or standard of care chemotherapy. Just over a thousand patients were randomly assigned to receive Imfinzi (346), Imfinzi plus tremelimumab (342), or chemotherapy (344). The median overall survival was 14.4 months in the Imfinzi monotherapy group versus 12.1 months in the chemotherapy group.
In the intention-to-treat population, which reflects the most generalizable results, the median overall survival was 15.1 months in the Imfinzi plus tremelimumab group versus 12.1 months in the chemotherapy group.The results were not statistically significant and so show that Imfinzi did not improve survival outcomes.