FDA panel questions Roche combo in breast cancer, votes to keep approval for now

 The FDA kicked off its three-day meeting on accelerated approvals of immuno-oncology drugs by picking apart one of the biggest players in the field, Roche’s Tecentriq, a PD-L1 inhibitor that the pharma giant has been counting on to replace sales lost to biosimilar competition on other blockbusters. In the end, advisers voted to keep the med's approval in place while further studies play out.

A panel of external experts summoned by the FDA spent the afternoon debating Roche on the benefits of combining Tecentriq with Abraxane (nab-paclitaxel) in PD-L1-positive metastatic triple-negative breast cancer (TNBC). Roche won a conditional nod in that indication based on the IMpassion130 trial, which showed the combo cut the rate of progression or death by 40% over Abraxane alone in PD-L1-positive patients.

The problem? The risk of death only fell 13% once PD-L1-negative patients were counted. And, in the confirmatory trial, IMpassion131, patients taking paclitaxel alone did better than those who took the combo treatment.

The "possible detriment in overall survival in the trial is very concerning," Laleh Amiri-Kordestani, M.D., director of the FDA's division of oncology, said during the meeting.

After tech issues disrupted the meeting, advisers voted 7-2 in favor of continued approval so investigators can collect more data on the combo.

During its presentation, Roche expressed confidence that future confirmatory trials would likely show the benefits of combining Tecentriq with Abraxane in TNBC. Meanwhile, the lack of effective therapies for women fighting TNBC supports leaving the combo on the market, said Stephen Chui, M.D., group medical director for oncology product development at Roche's Genentech.

"Chemotherapy has been the mainstay of therapy for triple negative breast cancer to date," Chui said. "Most of the other treatment options … have not reported survival benefits to date. Therefore the availability of anti-PD-L1 or anti-PD-1 treatment has offered another important therapeutic option for the approximately 40% of patients with TNBC tumors expressing PD-1," he added.

Several factors could have accounted for the differences in results from IMpassion130 and IMpassion131. Those include variations in premedication routines, differences in the statistical design of the trials and the fact that the median follow-up times were not the same.

Roche met with the FDA last December to discuss several options for generating confirmatory data, Chui said, including repeating the original pivotal clinical trial. A more practical solution would be to wait for data from three ongoing studies in related patient populations, including those with early TNBC, he added.

Roche has been downplaying the significance of this FDA panel review of accelerated cancer drug approvals. During the company’s first-quarter conference call last week, one analyst expressed worries that the confirmatory trial for the Tecentriq-Abraxane combination in TNBC “didn’t work,” and he pressed CEO Severin Schwan for details about how the company would persuade the agency to take a favorable position.

Schwan responded that “we'll do our best to make our case of why those are important indications,” before pointing out that nearly 90% of the prescriptions of Tecentriq are for lung cancer and hepatocellular carcinoma. TNBC and bladder cancer “aren't the most significant indications,” he said.

Maybe so, but any setback for Tecentriq would be a setback for Roche, which is facing a host of challenges to its flagship oncology business. During the first quarter, biosimilar competition to Roche’s Avastin, Herceptin and Rituxan pulled the company’s total oncology sales down 19%.

That only puts more pressure on Tecentriq, which brought in sales of 2.7 billion CHF ($3 billion) in 2020, up 55% from the previous year.

The drug is the target of a major life-cycle-building push at the cancer giant. Roche recently posted a major win in early-stage non-small cell lung cancer (NSCLC). In a trial of patients who had undergone surgery, the drug topped best supportive care at preventing disease recurrence or death.

But that win won’t necessarily translate into a sales bump. Roche’s pharma chief Bill Anderson estimated during the earnings call that the NSCLC market could be worth up to $3 billion a year, but it’s possible use of Tecentriq will be limited to patients with tumors that express PD-L1, which could limit its penetration. Competing PD-1/L1 inhibitors could be a factor, too, and analysts are worried oncologists won’t embrace Tecentriq in NSCLC without proof it meaningfully extends lives.

Tecentriq will be in the firing line again tomorrow afternoon when the FDA panel will discuss the merits of the drug in treating first-line bladder cancer patients.

https://www.fiercepharma.com/pharma/fda-panel-questions-benefits-roche-s-tecentriq-abraxane-combo-breast-cancer-threatening