Atezolizumab Benefits Survival vs Docetaxel Across Multiple Subtypes of Non–Small Cell Lung Cancer


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A wide range of patients with advanced non–small cell lung cancer (NSCLC) see a survival advantage from second- or third-line atezolizumab (Tecentriq) as compared with docetaxel, according to new data from the OAK trial.1

The main results of the randomized phase III trial, previously reported, showed that with a minimum follow-up of 19 months, the trial met its primary endpoint among all 850 patients included in the intent-to-treat analyses.2 Specifically, patients given the antibody, which targets the programmed cell death ligand 1 (PD-L1), had a 27% lower risk of death than counterparts given docetaxel. The benefit was similar regardless of the presence and extent of tumor expression of the ligand.

In the new subgroup analysis, atezolizumab reduced the risk of death compared with docetaxel, by 18% to 65%, regardless of how PD-L1 status was assessed (immunohistochemistry vs gene expression) and in patients differing with respect to tumor histology, age, smoking status, and presence of central nervous system (CNS) metastases, first author Shirish M. Gadgeel, MD, reported in a plenary session and related press conference. The lone exception was noted in patients with epidermal growth factor receptor (EGFR) mutations, who did not derive any greater benefit than docetaxel, as was seen in trials of other agents that inhibit programmed cell death protein 1 (PD-1) receptor.


Atezolizumab improved survival compared to docetaxel across all levels of PD-L1 expression, including in patients with low or no PD-L1 expression.
— Shirish M. Gadgeel, MD

“This subgroup analysis demonstrates a broad benefit with atezolizumab in NSCLC patients, and these results—both the primary and subgroup analyses—were recently published,”3 concluded Dr. Gadgeel, who is a medical oncologist and leader of the Thoracic Oncology Multidisciplinary Team at the Karmanos Cancer Center in Detroit.

Study Details

The OAK investigators recruited patients from North America, Central and South America, Europe, and the Asia-Pacific region who had received no more than two prior lines of therapy for advanced NSCLC, one of which must have included platinum-based chemotherapy. They were treated on an open-label basis with atezolizumab or docetaxel every 3 weeks. This is the first randomized phase III trial to evaluate an anti–PD-L1 in patients with NSCLC.

“Analysis of PD-L1 status as measured by two different methodologies—immunohistochemistry and PD-L1 gene expression—demonstrated that atezolizumab improved survival compared to docetaxel across all levels of PD-L1 expression, including in patients with low or no PD-L1 expression,” Dr. Gadgeel reported.

Survival Advantage

The benefit was seen in patients with squamous and nonsquamous tumors and, within each of those subgroups, among patients having the full range of PD-L1 expression (hazard ratio [HR] = 0.35–0.82).

Atezolizumab also conferred a survival advantage whether patients had CNS metastases (HR = 0.54) or not (HR = 0.75.) “Overall, the level of PD-L1 expression in patients with CNS metastases and patients without CNS metastases was fairly similar,” he noted.

Data reported in a companion poster showed that the incidence of new CNS lesions was essentially the same for the treatment arms, but the time to development of CNS metastases was longer with atezolizumab.4 Patients with CNS metastases did not see any additional toxicities from the antibody.

There was also a survival benefit in current or previous smokers (HR = 0.74) and in never-smokers (HR = 0.71). “Overall, the PD-L1 expression levels in patients who were never-smokers was somewhat lower than the PD-L1 expression in tumors of patients who were current or former smokers,” Dr. Gadgeel reported.

In age-stratified analyses, atezolizumab prolonged life relative to docetaxel among all age groups (HR = 0.63–0.80).

Although patients with EGFR wild-type tumors were less likely to die when given the antibody than when given chemotherapy (HR = 0.69), patients whose tumors harbored mutations in this gene did not see any such benefit. ■

Disclosure: Shirish M. Gadgeel, MD, is a consultant for Genentech/Roche, Pfizer, Bristol-Myers Squibb, Ariad, and AstraZeneca and is on the speakers bureau for
Genentech/Roche and AstraZeneca.

References

1. Gadgeel SM, Ciardiello F, Rittmeyer A, et al: OAK, a randomized phase III study of atezolizumab vs docetaxel in patients with advanced NSCLC: Results from subgroup analyses. 2016 World Conference on Lung Cancer. Abstract PL04a.02. Presented December 7, 2016.

2. Barlesi F, Park K, Ciardiello F, et al: Primary analysis from OAK, a randomized phase III study comparing atezolizumab with docetaxel in 2L/3L NSCLC. 2016 European Society for Medical Oncology. Abstract LBA44_PR. Presented October 10, 2016.

3. Rittmeyer A, Barlesi F, Waterkamp D, et al: Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicenter randomised controlled trial. Lancet. December 12, 2016 (early release online).

4. Lukas R, Gandhi M, O’Hear C, et al: Atezolizumab in advanced NSCLC patients with baseline brain metastases: A pooled cohort safety analysis. 2016 World Conference on Lung Cancer. Abstract P2.03b-014. Presented December 6, 2016.


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“The OAK subgroup analyses showed the benefit of atezolizumab (Tecentriq) virtually “across the board,” including among patients with programmed cell death...





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