ODAC votes to keep Keytruda and Tecentriq accelerated approvals in bladder cancer
The FDA’s Oncologic Drugs Advisory Committee is continuing to find it difficult to say no to cancer patients, especially as bladder cancer patients affected by Wednesday’s votes have few other treatment options.
On Wednesday morning, ODAC voted 5-3 in favor of keeping Keytruda’s (pembrolizumab) accelerated approval alive as a first line bladder cancer treatment for those who are cisplatin-ineligible and carboplatin-ineligible, even after a Merck confirmatory trial failed.
And on Wednesday afternoon, ODAC voted 10-1 in favor of keeping Genentech’s Tecentriq (atezolizumab) as a first-line treatment of cisplatin-ineligible patients with advanced/metastatic bladder cancer pending final overall survival results from a confirmatory trial, known as IMvigor130.
Among those voting in favor of Keytruda — Merck’s mega-blockbuster drug, with 19 full approvals, including a full approval as a second-line bladder cancer treatment, and 10 accelerated approvals — several physicians pointed to the lack of other treatments for certain patients.
While the confirmatory trial did not show a benefit for Keytruda as a first-line treatment, much of the discussion centered on these subgroups of patients who might have no treatment options without Keytruda.
“Access to pembrolizumab remains important for these patients, and FDA approval should be maintained until additional confirmatory data are available,” Peter Kang, VP of clinical research at Merck, told the committee.
As far as how Merck might still confirm benefit in this indication, Kang pointed to one study that would look at Keytruda in combination with Eisai’s Lenvima, compared with Keytruda and placebo. That trial is expected to be completed in October 2023. But the FDA said it would be challenging to use this trial as it does not isolate the effect of Keytruda. Two other potential confirmatory trials from Merck may also be used to confirm its benefit, and are expected to finish in mid-2025 and 2027.
Laying out the case for FDA, Laleh Amiri-Kordestani, division director in FDA’s Office of Oncologic Diseases, noted that the clinical trial evidence does not support continued approval for Keytruda in this setting.
She also explained how the treatment landscape has changed, as last June, FDA approved EMD Serono’s Bavencio (avelumab) for those with bladder cancer who have not progressed with first-line platinum-containing chemotherapy.
But Ronac Mamtani, bladder cancer doctor at the University of Pennsylvania, took to the public forum at the meeting and stressed what other panelists had been hinting at — that retaining this indication could be critical for some patients who are cisplatin-ineligible.
For the afternoon session, panelists were overwhelmingly in favor of waiting for the overall survival results from a confirmatory trial to read out for Tecentriq before deciding on whether to pull the bladder cancer indication.
Mohummad Siddiqui, director of urologic oncology at the University of Maryland Medical Center, voted to keep this accelerated approval for Tecentriq and said the interim analysis looks promising and the FDA should wait for the final analysis from IMvigor130. And Rick Pazdur, FDA’s top oncology head, sweetened the offer for Roche/Genetech, noting that if the company hits on the overall survival in the trial, they’ll be able to convert the Tecentriq monotherapy accelerated approval to full approval and the company will win a new indication for Tecentriq in combination with chemo.
Philip Hoffman, chair of ODAC, was the only committee member to vote against keeping this Tecentriq accelerated approval, and he said he was concerned by withdrawal of the Roche/Genentech drug in the second line setting as the primary endpoint of overall survival was not met.
The votes on Wednesday followed Tuesday’s meeting, in which committee members voted 7-2 to keep alive the accelerated approval for Genentech’s Tecentriq (atezolizumab) plus Abraxane (nab-paclitaxel) in metastatic triple negative breast cancer (mTNBC) while additional confirmatory trials are ongoing.
Three more accelerated approvals (including two for Keytruda and one for Bristol Myers Squibb’s Opdivo) are set for votes on Thursday. While the FDA does not have to follow the advice of ODAC, it generally does.