Merck & Co’s Keytruda and Roche’s Tecentriq should stay on the market as first-line treatments for bladder cancer, at least until new clinical data becomes available next year.
That was the conclusion at the second day of a meeting of the FDA’s Oncologic Drugs Advisory Committee (ODAC), convened to discuss three immuno-oncology drugs granted conditional approvals in six cancers that subsequently failed studies designed to confirm their benefits.
Yesterday, the ODAC turned its attention to the accelerated approvals awarded to Keytruda (pembrolizumab) and Tecentriq (atezolizumab) as first-line treatments for cisplatin-ineligible patients with urothelial carcinoma (UC), the most common form of bladder cancer.
The panel voted three to five in favour of Keytruda, and ten to one in favour of Tecentriq, to recommend that the indication should be kept on their list of approved indications. While the ODAC’s vote is non-binding the FDA seldom overrules the conclusions of its expert advisers.
Earlier, the ODAC also voted seven to two to retain Tecentriq’s approval for triple-negative breast cancer (TNBC), indicating that panel members are minded to support use of these drugs – even with limited evidence – when there are few other treatment options available.
The first-line bladder cancer deliberations were considered to be among those at highest risk of being voted down, in part because a third immuno-oncology drug – Merck KGaA/Pfizer’s Bavencio (avelumab) – is approved as a first-line maintenance therapy with a demonstrated benefit on survival in a phase 3 trial.
The Keytruda discussions were finely balanced, with some panellists suggesting that the drug’s use in previously-untreated UC could be limited to patients who aren’t able to tolerate any platinum-based chemotherapies. At the moment, Keytruda can also be prescribed as an alternative to other platinum drugs like carboplatin in cisplatin-ineligible patients whose tumours express PD-L1.
The FDA could feasibly opt to restrict its use to patients ineligible for any platinum therapy, as Bavencio is an option for the cisplatin-ineligible group, but may keep the status quo until data from a new study called LEAP-011 becomes available.
LEAP-011 isn’t a direct confirmatory trial as it is comparing Keytruda plus Eisai’s Lenvima (lenvatinib) to Keytruda alone in PD-L1-positive, cisplatin-ineligible patients, but will build on the dataset for Keytruda as a monotherapy for these patients.
The deliberations on Tecentriq were more straightforward, in part because its confirmatory trial IMvigor130 only narrowly missed showing a statistically significant improvement in survival when it was used to treat cisplatin-ineligible UC patients with PD-L1 expression of 5% or more.
All but one of the ODAC felt that the indication should be retained pending final overall survival results from IMvigor130, which are due next year.
The single no voter – Phillip Hoffman of the University of Chicago – said he did so in part because Tecentriq failed a trial as a second-line treatment for bladder cancer, which resulted in Roche withdrawing the drug for that indication.
At the halfway point with all three accelerated approvals retained, the ODAC will turn its attention today to Keytruda for third-line treatment of recurrent, PD-L1-expressing gastric or gastroesophageal junction adenocarcinoma, and the approvals of Keytruda and Bristol-Myers Squibb’s Opdivo (nivolumab) as second-line therapies for hepatocellular carcinoma (HCC) previously treated with Bayer/Onyx’ Nexavar (sorafenib).
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