Roche pulls dangling accelerated approval for Tecentriq in triple-negative breast cancer
Roche on Friday decided to voluntarily pull an indication won via the FDA’s accelerated approval pathway for its blockbuster PD-L1 drug Tecentriq.
This is the third accelerated approval to be pulled following an ODAC meeting last April to review six indications from Roche, Merck and Bristol Myers Squibb blockbuster cancer drugs, where confirmatory trials failed. This is also the fourth accelerated approval to be pulled in the last month.
The move to pull Tecentriq in combination with chemo for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer comes after the FDA’s oncologic drugs adcomm voted 7-2 to keep it dangling, while other, additional confirmatory trials were ongoing.
But Roche said it came to its decision after recent conversations with FDA on another postmarketing trial, and “due to the recent changes in the treatment landscape,” which the company said means that the FDA “no longer considers it appropriate to maintain the accelerated approval.”
With limited other treatment options at the time, Tecentriq initially won its accelerated OK 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 of 7.4 months, which compared with 4.8 months for those on placebo in combo with nab-paclitaxel.
But 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 at the ODAC meeting and noted the overall survival results in the initial trial (on which the accelerated approval was based) may have been due to chance alone, and that the benefit seen in the first trial was not corroborated in a similar population in the confirmatory trial.
Roche emphasized that Friday’s decision only impacts the mTNBC indication in the US and does not affect other approved indications for Tecentriq in the US and outside the US. In 2020, Tecentriq brought in almost $3 billion in worldwide sales.
Also following that high-stakes April ODAC meeting, Merck last month agreed to pull a third-line stomach cancer indication for its blockbuster Keytruda, which received a thumbs down from ODAC after late-stage confirmatory trials failed to show clinical benefit. And Bristol Myers late last month also pulled an indication reviewed by ODAC for Opdivo as a monotherapy for hepatocellular carcinoma patients who have previously been treated with sorafenib.
Overall, the outside experts voted to recommend pulling two of the six indications reviewed, both of which have now been pulled, in addition to Roche’s decision. It remains unknown what may come for the other two indications reviewed at the meeting.
Separately, Bristol Myers in early August also pulled an Istodax indication in peripheral T cell lymphoma after a Phase III confirmatory study for the drug flopped on its progression-free survival endpoint.