Tech glitches overshadow FDA oncology adcomm as a solid majority of advisers vote to keep Roche's Tecentriq in mTNBC
Kicking off three days of reexamining anti-PD(L)-1 accelerated approvals, the FDA’s Oncologic Drugs Advisory Committee started slowly on Tuesday. After a more than hour-long technical delay, 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.
But technical glitches at the hearing kept discussions among the committee’s cancer experts to only a few questions for Genentech, and the audio cut out before the committee members offered any of their typical explanations after their votes.
Triple-negative breast cancer (TNBC) is notoriously difficult to treat, representing 10-20% of breast cancers, with a median survival after diagnosis of just 12 to 18 months and a 5-year survival rate of 15%, explained Charlie Fuchs, a Yale cancer specialist who joined Roche in January.
The good: With limited other treatment options, Tecentriq initially won its accelerated approval in combination with nab-paclitaxel for adult patients with mTNBC whose tumors express PD-L1 in March 2019 based on a median progression-free survival (PFS) of 7.4 months, which compared with 4.8 months for those on placebo in combo with nab-paclitaxel.
The bad: The confirmatory trial did not pan out, and even showed a worrisome sign as the placebo outperformed the treatment combo in terms of overall survival.
Laleh Amiri-Kordestani, division director at the Office of Oncologic Diseases, presented for the FDA on Tuesday and also noted that the overall survival results in the initial trial (on which the accelerated approval is based) may be due to chance alone, and that the benefit seen in the first trial was not corroborated in a similar population in the confirmatory trial.
The ugly: She also called the overall survival results in the confirmatory trial “concerning.” Those results led to an alert from the agency and a label update in December because of the “possibility of detriment” in overall survival.
Presenting for Genentech, Steve Chui, global development lead in oncology, spelled out both the benefit from the initial trial and how the confirmatory trial did not show a PFS benefit. He also explained how the results from the confirmatory trial showed 101 of those on placebo and paclitaxel had a median of 28.3 months of overall survival, compared with 22.1 months for 191 of those on atezolizumab and paclitaxel.
Looking to the future, Chui pointed to conversations from December with FDA on other possible confirmatory trials, including one that would use a different type of chemo along with Tecentriq in about 570 mTNBC patients, which is expected to see results in 2023. Other trials proposed won’t read out until 2023 or 2024.
The FDA said in its briefing documents that “it is not yet clear which of these trials are sufficiently designed to adequately confirm benefit,” and adcomm panelists questioned why one of the trials would use different chemotherapies if it’s a confirmatory trial for Tecentriq and nab-paclitaxel. But the majority of members still voted to keep the indication under an accelerated approval.
Prior to the discussion of atezolizumab, Julia Beaver, chief of medical oncology at FDA’s Oncology Center of Excellence, opened the meeting by explaining how accelerated approvals only need to be “reasonably likely to predict clinical benefit,” and that of the 151 accelerated approvals for oncology drugs, 35 have been for PD-(L)1 antibodies, including the three under scrutiny this week, and a total of 10 have been withdrawn.
Those withdrawals have come as the treatment landscape may have changed or because follow-up trials have failed to confirm benefits.