FDA Approves Tecentriq/Chemo for Newly Diagnosed Extensive-stage SCLC

The U.S. Food and Drug Administration has approved the use of Tecentriq (atezolizumab) in combination with the chemotherapies Paraplatin (carboplatin) and etoposar for the initial treatment of extensive-stage small-cell lung cancer patients.

The approval, which makes Tecentriq the first immunotherapy approved for this indication, is based on findings from the IMpower133 Phase 3 trial (NCT02763579), where this combination significantly extended patients’ lives and delayed disease worsening or death, compared to chemotherapy only.

“Extensive-stage small cell lung cancer is a highly aggressive form of lung cancer, which until now has seen limited treatment advances over the last 20 years,” Andrea Ferris, president and CEO of LUNGevity Foundation, said in a press release. “[The] approval of Tecentriq is an important step forward in ensuring that people across the spectrum of lung cancer types have effective new therapies.”

Tecentriq, by Genentech, a member of the Roche group, is an immune checkpoint inhibitor that binds to the PD-1 receptor on immune cells and prevents the binding of the PD-L1 ligand produced by cancer cells. Cancer cells use this mechanism to evade immune surveillance, and thus, Tecentriq is meant to restore a functional immune system that effectively fights cancer.

Research has shown that cancers with high mutation burden, like small cell lung cancers, respond better to immune checkpoint inhibitors. And while studies of Keytruda (pembrolizumab) and Yervoy (ipilimumab) showed no added benefit to chemotherapy, Tecentriq showed a promising duration of response in a Phase 1 trial (NCT01375842) for relapsed or refractory small-cell lung cancer patients.

Based on the findings, researchers at Roche designed IMpower133 to determine whether a combination of Tecentriq and chemotherapy could improve the survival outcomes of extensive-stage small cell lung cancer patients who had not received any prior treatment.

The trial included 201 patients who were randomly assigned Tecentriq plus chemotherapy —Paraplatin and etoposar — or placebo plus chemotherapy. After four cycles of the combination, patients received Tecentriq or placebo as maintenance treatment, which was continued until disease progression or intolerable toxicity.

Investigators found that Tecentriq significantly extended survival from 10.3 to 12.3 months, representing a 30% reduction in the risk of death. Similarly, the risk of disease progression or death was lowered by 27%, with Tecentriq-treated patients living a median of 5.2 months before their disease worsened, compared to 4.3 months for the chemotherapy group.

Responses were similar across both groups, with 60.2% of patients in the Tecentriq group achieving a partial or complete response, compared to 64.4% of those on chemotherapy. Duration of responses were also similar.

The combination also led to a similar proportion of patients experiencing adverse events — 37% vs. 35% for chemotherapy. Immune-related adverse events, however, were more common in the Tecentriq group. The most common adverse reactions were fatigue, nausea, hair loss, decreased appetite, constipation, and vomiting.

“Tecentriq is the first cancer immunotherapy approved for the initial treatment of extensive-stage small cell lung cancer, which is especially difficult to treat,” said Sandra Horning, MD, chief medical officer and head of global product development for Genentech. “Until now, there have been limited treatment advances for this disease, and we are excited to bring a potential new standard of care to patients that has been shown to improve survival compared to chemotherapy.”

Tecentriq is also approved for certain bladder, non-small cell lung, and triple-negative breast cancers. For people who qualify for Tecentriq, Genentech offers patient assistance programs through Genentech Access Solutions.