AT ESMO 2016
COPENHAGEN (FRONTLINE MEDICAL NEWS) – The checkpoint inhibitor atezolizumab improved overall survival of advanced non–small-cell lung cancer, compared with docetaxel, primary analysis from the OAK trial shows.
In the first phase III trial of a monoclonal antibody directed against the programmed death 1 ligand (PD-L1) in non–small-lung cell lung cancer (NSCLC), median overall survival (OS) for patients assigned to atezolizumab (Tecentriq) was 13.8 months, compared with 9.6 months for patients assigned to docetaxel, reported Fabrice Barlesi, MD, head of the multidisciplinary oncology and therapeutic innovations department at Aix-Marseille University and the Assistance Publique Hôpitaux de Marseille, France.
“Atezolizumab was well tolerated with a favorable safety profile compared to docetaxel. No new safety signals were identified, and the rate of immune-mediated adverse events was very low,” he said at the European Society for Medical Oncology Congress.
Atezolizumab was previously shown in the phase II POPLAR trial to significantly increase overall survival compared with docetaxel in second- or third-line therapy in patients with locally advanced or metastatic NSCLC who had disease progression after platinum-based chemotherapy.
The OAK trial investigators enrolled 1,225 patients with locally advanced or metastatic NSCLC following one or two prior lines of therapy that contained at least one platinum-based regimen. The patients could have any degree of PD-L1 expression.
Dr. Barlesi presented results of a prespecified intention-to-treat analysis of the first 850 patients enrolled.
Following stratification for PD-L1, histology, and prior chemotherapy regimens, they were randomly assigned to either atezolizumab 1,200 mg IV every 3 weeks or docetaxel 75 mg/m2 every 3 weeks. In the atezolizumab arm, therapy could be continued until disease progression or clinical benefit. In the docetaxel arm, therapy was continued until progression.
As noted, atezolizumab was associated with significantly better OS, the primary endpoint (13.8 vs. 9.6 months) with a hazard ratio (HR) of 0.73 (P = .0003). OS rates at 12 months were 55% in the atezolizumab arm vs. 41% in the docetaxel arm, and at 18 months the rates were 40% and 27%, respectively.
The investigators found that atezolizumab provided a benefit regardless of PD-L1 expression, with a hazard ratio of 0.74 (P = .0102) for the 55% of patients with PD-L1 expression on at least 1% of their tumor cells, and 0.75 (P = .0205) for patients with PD-L1 on less than 1% of tumor cells.
Median overall survival was greater with both drugs for patients with higher levels of PD-L1 expression, with a median of 15.7 months for those treated with atezolizumab and 10.3 months for those treated with docetaxel. In contrast, the respective median overall survival durations in the patients with less than 1% PD-L1 expression were 12.6 and 8.9 months.
The greatest benefit for atezolizumab was seen in patients with PD-L1 expression of 50% or more of tumor cells or 10% or more of tumor-infiltrating immune cells, with a median OS at a minimum follow-up of 19 months of 20.5 months vs. 8.9 months, translating into a hazard ratio for atezolizumab of 0.41 (P less than .0001).
An analysis of OS by histology showed HRs of 0.73 for atezolizumab for patients with either non-squamous tumors (P = .0015) or squamous tumors (P = .0383). In addition, an analysis of OS in selected subgroups showed a trend favoring atezolizumab in patients who had never smoked, who tend to have a worse prognosis than would current or former smokers.
In an analysis of progression-free survival, there was no significant difference between the groups (median 4.0 vs. 2.8 months).
Adverse events of grade 3 or greater of any cause were lower with atezolizumab, at 37% vs. 54%. There was one treatment-related death from respiratory infection in a patient who received docetaxel.
Invited discussant Naiyer Rizvi, MD, an oncologist at Columbia University Medical Center in New York, said that the OAK trial confirms that atezolizumab is an appropriate second-line therapy for unselected patients with advanced NSCLC, and should be explored for its potential survival benefits in never smokers.