TORONTO – Adding the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab to standard first-line chemotherapy and maintenance therapy in patients with advanced nonsquamous non–small-cell lung cancer significantly improved progression-free survival (PFS), in the randomized, open-label IMpower132 trial.
At a minimum follow-up of 11.7 months (median, 14.8 months), investigator-assessed median PFS in 292 patients enrolled in the atezolizumab arm of the global study was 7.6 months, compared with 5.2 months – a 40% reduction in risk of disease progression – in 286 patients who received only first-line carboplatin plus pemetrexed and pemetrexed maintenance therapy (hazard ratio, 0.60), Vassiliki A Papadimitrakopoulou, MD, reported at the Worldon Lung Cancer.
“The landmark PFS at 12-months showed almost a doubling for the investigational arm [at] 33.7% vs. 17%,” said Dr. Papadimitrakopoulou, professor of medicine and chief of the section of thoracic medical oncology at MD Anderson Cancer Center in Houston. “PFS benefit was seen across all key subgroups, [and was] especially pronounced for female patients (HR, 0.51), Asian patients (HR, 0.42), never-smokers (HR, 0.49), and patients who didn’t have liver metastases (HR, 0.56).”
PFS was also looked at – as an exploratory endpoint – by PD-L1 status in biomarker-evaluable patients, and “again, benefit was seen across all PD-L1-defined subgroups with a consistent trend for most benefit among the highest expressers,” she noted.
Median PFS was 10.8 months in 25 atezolizumab-treated patients with high PD-L1 expression, vs. 6.5 months in 20 control group patients with high PD-L1 expression; 6.2 vs. 5.7 months in 63 and 73 patients with low-PD-L1 expression in the groups, respectively; and 8.5 vs. 4.9 months in 88 and 75 PD-L1-negative patients in the groups, respectively, she reported at the conference, which was sponsored by the International Association for the Study of Lung Cancer.
Interim analyses also showed a numerically superior improvement in median and 12-month overall survival in the atezolizumab vs. control group (median, 18.1 vs. 13.6 months; HR, 0.813; P = .0797; 12-month, 59.6% vs. 55.4%), she said, adding that overall survival will be looked at again at the final analysis of the data, which is anticipated some time in the first half of 2019.
Study participants were chemotherapy-naive patients with measurable stage IV nonsquamous NSCLC and Eastern Cooperative Oncology Group Performance Status 0-1. Those with tumors known to harbor epidermal growth factor receptor or anaplastic lymphoma kinase driver mutations were excluded, as were those with untreated central nervous system metastases, autoimmune disease, and prior exposure to immunotherapy.
All patients received four or six cycles of carboplatin at a dose of area under the curve 6 mg/mL/min or cisplatin at a dose of 75 mg/m2 plus 500 mg/m2 of pemetrexed every 3 weeks, and those in the experimental arm also received 1,200 mg of atezolizumab every 3 weeks. Maintenance therapy included pemetrexed alone in the control arm, and atezolizumab plus pemetrexed in the experimental arm.
Treatment was well tolerated, and no new safety signals emerged, Dr. Papadimitrakopoulou said, noting that adverse events were similar in the groups, but more common in the atezolizumab-treated patients. Grade 3-4 treatment-related adverse events occurred in 54% of patients receiving atezolizumab vs. 39% of those in the control group, and serious adverse events occurred in 33% vs. 16%.
“The findings from IMpower132 indicate that the addition of atezolizumab to a backbone of carboplatin and pemetrexed chemotherapy provides better clinical efficacy than carboplatin and pemetrexed alone,” Dr. Papadimitrakopoulou said in a press statement. “By inhibiting the interaction of PD-L1 with its receptors PD-1 and B7.1, atezolizumab restores tumor-specific T-cell immunity, offering a valuable treatment option that prolongs survival for patients with stage IV nonsquamous NSCLC.”
IMpower132 is sponsored by F. Hoffmann–La Roche Ltd. Dr. Papadimitrakopoulou has received research support from, and/or is an advisory board member for numerous companies including F. Hoffmann–La Roche.
SOURCE: Papadimitrakopoulou V et al. WCLC 2018 Abstract .