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Atezolizumab Immunotherapy Extends Overall Survival in Lung Cancer

Goodwin, Peter M.

doi: 10.1097/01.COT.0000512070.81903.78
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COPENHAGEN, DENMARK—The anti-PD-L1 (programmed cell death ligand-1) immunotherapy agent atezolizumab extended overall survival when compared head-to-head with docetaxel among patients with previously-treated non-small cell lung cancer (NSCLC) in the phase III OAK study reported at the European Society for Medical Oncology 2016 Congress (Abstract LBA44_PR).

Lead author Fabrice Barlesi, MD, PhD, Professor of Medicine at the Department of Multidisciplinary Oncology and Therapeutic Innovations of Assistance Publique Hôpitaux de Marseille, Aix-Marseille University in France, reported an overall hazard ratio of 0.73 in favor of immunotherapy among the first 850 patients—of whom those treated with atezolizumab lived more than 4 months longer than those receiving docetaxel (13.8 months as compared with 9.6 months median).

Because the agent targets the PD-L1 protein, it was expected to be more effective in patients testing positive for PD-L1, and the OAK study indeed found greater efficacy in this biomarker-positive group. Yet, the drug clearly benefited patients in other subgroups as well.

“The important message is that we have an immunotherapy treatment that works for all the patients in the second-line setting—whatever the PD-L1 status, and whatever the clinical characteristics—and it provides doctors and patients with a new strong therapeutic option,” Barlesi told Oncology Times.

ESMO officer Solange Peters, MD, PhD, Médecin Cheffe for Thoracic Malignancies at the Centre Hospitalier Universitaire Vaudois, University of Lausanne in Switzerland, noted the trial had brought clarification about the role of immunotherapy in lung cancer.

“What we knew from the other trials is that it's better to give immunotherapy than docetaxel. In terms of survival, [it is] very obviously better. This trial confirms that the higher PD-L1 is expressed the stronger is the benefit. But this trial clearly shows that patients without expression of PD-L1—the biomarker-negative population—still benefit from atezolizumab,” she explained.

Barlesi said that the idea of using a PD-L1-directed drug arose because such “checkpoint inhibitors” work by cancelling one of the mechanisms cancer cells use to evade the immune system.

“The goal of this treatment is to allow the immune system to control and possibly eliminate cancer calls, so atezolizumab might be useful in a very large setting of different cancers,” said Barlesi.

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OAK Study Specifics

The OAK study enrolled 1,225 patients with previously-treated NSCLC and—after stratifying them according to PD-L1 status, number of prior chemotherapy regimens, and histology—randomized them to IV atezolizumab (1,200 mg every 3 weeks) or docetaxel (75 mg/m2 every 3 weeks).

While the study was able to quantify the benefit from treatment with the PD-L1 checkpoint inhibitor in all patients, the study also was designed to look at subgroups, with patients stratified according to their levels of PD-L1 expression.

Patients with more than 1 percent expression of the PD-L1 biomarker lived 52 percent longer if they received immunotherapy (15.7 months median compared with 10.3 months for docetaxel).

And patients in the highest group of PD-L1 expression treated with atezolizumab lived more than a year longer—to a median of 20.5 months as compared with 8.9 months for matched patients receiving docetaxel.

But even the patients who had no PD-L1 expression lived longer (12.6 as compared with 8.9 months median) with immunotherapy than with chemotherapy. And the improvements in overall survival were similar in patients with squamous and non-squamous histology.

Moderate-to-severe treatment-related adverse events occurred in 15 percent of patients treated with immunotherapy as compared with 43 percent of those receiving chemotherapy. There were no deaths related to atezolizumab and one death was related to docetaxel.

“Atezolizumab offers a new second-line therapeutic strategy for patients with non-small-cell lung cancer, regardless of the PD-L1 status of the tumor,” Barlesi said.

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Predicting Success of Atezolizumab

Martin Reck, MD, PhD, from the Department of Thoracic Oncology at Lung Clinic Grosshansdorf in Germany, commented that the OAK study had provided “a very important piece of information” on the role of PD-L1/PD-1 antibodies in treatment of NSCLC, and it confirmed the overall survival benefits shown in the earlier POPLAR and CHECKMATE trials.

But he said the results show it would not be possible to use PD-L1 testing negativity as an exclusion factor for treatment since the drug benefited all subgroups.

“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,” he noted.

Stefan Zimmermann, MD, from Hôpital Fribourgeois, HFR Hôpital Cantonal, Fribourg, Switzerland, who chaired a briefing on the OAK findings at ESMO told Oncology Times the new data on atezolizumab needed to be viewed in the context of other studies with other checkpoint inhibitors.

“It reinforces the message that in second and further lines of therapy there is benefit even in patients who have low or no expression of PD-L1,” he said, and his interpretation of the data was that “you don't need an assay”, since most—if not all—subgroups benefit from an immune-oncology approach rather than standard chemotherapy.

“I can imagine that atezolizumab will get regulatory approval so we'll now have a wealth of choices in second and further lines. We [already] have nivolumab that has regulatory approval, we have pembrolizumab in second line for PD-L1-espressing patients, and we might [soon] have atezolizumab,” he concluded.

Peter M. Goodwin is a contributing writer.

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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