Atezolizumab: First PD-L1 Inhibitor for Second-Line NSCLC

Zosia Chustecka

October 17, 2016

COPENHAGEN, Denmark – A slightly different immunotherapy has shown benefit in the second-line treatment of non–small cell lung cancer (NSCLC).

New data are the first to show that the programmed cell death ligand 1 (PD-L1) atezolizumab (Tecentriq, Genentech/Roche) outperforms chemotherapy in this setting. Hence, it looks set to soon join the two PD inhibitors nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck & Co) that are already approved for second-line use in NSCLC.

Atezolizumab is currently approved for use in bladder cancer but is being explored in many other tumor types.

The new data come from the phase 3 OAK study and were reported here at a presidential session during the European Society for Medical Oncology (ESMO) Congress.

It was conducted in 1225 patients with previously treated NSCLC. After being stratified according to PD-L1 status, number of prior chemotherapy regimens, and histology, the patients were randomly allocated to receive either intravenous atezolizumab (1200 mg every 3 weeks) or docetaxel (75 mg/m2 every 3 weeks).

At the meeting, a preliminary analysis from the first 850 patients was presented by Fabrice Barlesi, MD, from the Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France.

Dr Fabrice Barlesi

He reported a 27% improvement in overall survival (OS) with the immunotherapy; the median OS was 13.8 months vs 9.6 months on docetaxel (hazard ratio [HR], 0.73; P = .0003).

The median OS was significantly better with immunotherapy in all subgroups of patients, regardless of their PD-L1 expression levels, including patients with PD-L1 expression of less than 1%. The survival benefit was seen in NSCLC with both squamous and nonsquamous histology (HR = 0.73 for each) and was also seen in nonsmokers (HR = 0.71), Dr Barlesi noted.

The subgroup of patients with the highest levels of PD-L1 expression (TC3 group, n = 72) had the most benefit from immunotherapy; OS was 59% greater in patients receiving atezolizumab, (median OS, 20.5 months vs 8.9 months with docetaxel; HR, 0.41; P < .0001).

"Azetizolumab offers a new second-line therapeutic strategy for patients with non–small cell lung cancer, regardless of the PD-L1 status of the tumor," Dr Barlesi concluded.

It was also better tolerated than chemotherapy, and the rate of immune-related adverse events was low, he said. Grade 3-4 treatment-related adverse events occurred in 15% of patients receiving atezolizumab and 43% of patients receiving docetaxel. There were no deaths related to atezolizumab; one death was related to docetaxel, he added.

Discussing this study, Naiyer Rivzi, MD, from Columbia University Medical Center, New York City, said atezoluzimab showed a slightly different safety profile from the profiles previously seen with PD inhibitors nivolumab and pembrolizumab, and the efficacy was slightly different; he particularly noted, "Its efficacy in never-smokers was compelling."

Dr Rivzi said that on the basis of these data from the phase 3 OAK study, he would expect atezolizumab to be approved for second-line use in NSCLC without restrictions, based on PD-L1 expression.

Commenting on the study in an ESMO press release, Martin Reck, MD, from the Department of Thoracic Oncology at Lung Clinic Grosshansdorf, Germany, pointed out that the study "showed an improvement in overall survival even in patients with no PD-L1 expression, which means we have a problem with using PD-L1 negativity as an exclusion factor for treatment.

"My suggestion would be that PD-L1 is perhaps one imperfect surrogate marker to describe the activity. It's a good enrichment factor, but we need additional markers for the characterization of patients who might not benefit from this treatment or who might really benefit," Dr Reck commented.

The study was funded by Roche. Dr Bartesi has disclosed no relevant financial relationships. Six coauthors are Genentech employees, and several others have relationships with other pharmaceutical companies.

European Society for Medical Oncology (ESMO) Congress. Abstract LBA44_PR. Presented October 9, 2016.


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