Last month, Roche’s Tecentriq chalked up a surprising failure when used in tandem with chemotherapy paclitaxel in triple negative breast cancer (TNBC). The FDA has taken notice, issuing a warning that might spell trouble for a conditional nod of the PD-L1 agent.
On Tuesday, the FDA alerted the public that the Tecentriq-paclitaxel combo didn’t work in a clinical trial in previously untreated locally advanced or metastatic TNBC and warned doctors not to use it.
The thing is, Tecentriq already holds a similar approval in TNBC, which it won in March 2019—and it’s that nod that could be in jeopardy. “Continued approval … may be contingent on proven benefit of the treatment in additional trials,” the FDA said.
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Tecentriq’s green light, restricted to PD-L1-expressing cases, is for a combination with Celgene’s Abraxane, or paclitaxel protein-bound, a formulation where paclitaxel is bound to albumin nanoparticles in a delivery mechanism that helps the drug concentrate in areas of tumor.
That conditional approval was based on data from the phase 3 IMpassion130 study, which showed that Tecentriq-Abraxane cut the risk of disease worsening or death by 40% over Abraxane alone in PD-L1-positive, previously untreated TNBC patients.
However, in the phase 3 IMpassion131 trial, adding Tecentriq to paclitaxel didn’t stall tumor progression in newly diagnosed PD-L1-positive patients. To make it worse, interim results even favored solo paclitaxel in terms of life extension, though Roche said the data were not conclusive.
Based on the latest trial failure, the agency said it would review the findings and announce any changes to Tecentriq’s prescribing information.
In a statement, a spokesperson at Roche’s Genentech declined to comment on whether the IMpassion131 failure might affect Tecentriq’s approved TNBC use, only saying the company is in active discussions with the FDA.
Of course, IMpassion131 might not threaten the existing indication after all. First, compared with conventional paclitaxel, Abraxane is linked to preferential uptake into cancer cells and, hence, potentially offers a better anti-tumor effect thanks to its unique delivery tech.
Plus, I-O drugs have put up failures in confirmatory trials before, but so far none have led to the FDA terminating an approval. Tecentriq itself in 2017 flopped a phase 3 trial in previously untreated bladder cancer, but it still got to keep a go-ahead based on phase 2 tumor response data. In June, Merck & Co.’s rival PD-1 drug Keytruda, whether on its own or used in combination with chemotherapy, also failed to significantly keep bladder tumors at bay compared with chemo. But that drug may not lose its conditional approval, either; there’s no word yet from the FDA.