IASLC World Conference on Lung Cancer
IASLC World Conference on Lung Cancer
Perspective from John Heinzerling, MD
September 28, 2018
2 min read
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Durvalumab extends OS in advanced lung cancer

Perspective from John Heinzerling, MD
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Durvalumab prolonged OS among patients with locally advanced, unresectable stage III non-small cell lung cancer that did not progress following chemoradiotherapy, according to results of the multicenter, randomized, placebo-controlled phase 3 PACIFIC trial presented at International Association for the Study of Lung Cancer’s World Conference on Lung Cancer.

“Results of PACIFIC provide compelling evidence for the unprecedented benefit of durvalumab [Imfinzi, AstraZeneca] as the standard of care in this patient population,” Scott J. Antonia, MD, PhD, chair of the thoracic oncology department at H. Lee Moffitt Cancer Center and Research Institute and professor of oncologic sciences at University of South Florida College of Medicine, said in a press release. “Durvalumab offers the first major advance in this disease setting in many years, offering new hope to patients with stage III, unresectable non-small cell lung cancer without progression after chemoradiotherapy.”

Disease progression is common after chemoradiotherapy, with 5-year OS rates of 15% to 30% and a median OS not exceeding 28 months. Although previous studies have evaluated systemic therapy after patients achieved disease control with chemoradiotherapy, these therapies have largely been ineffective.

Preclinical evidence suggested that chemoradiotherapy upregulates PD-L1 expression in tumor cells, which may enhance the efficacy subsequent treatment with PD-L1 blockade.

Earlier analysis of patient-reported outcomes of the PACIFIC study — presented at last year’s World Conference on Lung Cancer — showed durvalumab extended PFS compared with placebo. The current analysis includes updated data on the secondary primary endpoint of OS.

trial. Secondary endpoints included the time to death or distant metastasis, the time to second progression, 2-year OS and safety.

The double-blind trial included 709 patients treated across 235 centers in 26 countries.

Researchers randomly assigned 473 patients to 10 mg/kg IV durvalumab every 2 weeks and 236 patients to placebo. Patients were enrolled regardless of PD-L1 status and were stratified by gender, age and smoking history.

Median follow-up was 25.2 months (range, 0.2-43.1 months).

Results — published simultaneously in The New England Journal of Medicine — showed a 2-year OS rate of 66.3% (95% CI, 61.7-70.4) among those treated with durvalumab compared with 55.6% (95% CI, 48.9-61.8; two-sided P = .005) among those assigned placebo. Durvalumab significantly prolonged OS (stratified HR for death = 0.68; 99.73% CI, 0.47-0.99), regardless of PD-L1 expression.

Updated data on PFS was similar to what was previously reported. The median PFS was 17.2 months with durvalumab compared with 5.6 months with placebo (stratified HR for disease progression or death = 0.51; 95% CI, 0.41-0.63).

Median time to death or distant metastasis was 28.3 months with durvalumab compared with 16.2 months with placebo (stratified HR = 0.53; 95% CI, 0.41-0.68).

“With the between-group difference in median PFS remaining more than 11 months, the results of the analysis of OS indicate that the PFS benefit has translated to a significant prolongation in OS,” the researchers wrote.

Grade 3 or grade 4 adverse events of any cause occurred among 30.5% of those on the durvalumab arm compared with 26.1% of the placebo arm. Treatment discontinuation due to adverse events occurred among 15.4% of those assigned durvalumab vs. 9.8% assigned placebo. – by Jennifer Southall

References:

Antonia SJ, et al. Abstract PL02.01. Presented at: International Association for the Study of Lung Cancer’s World Conference on Lung Cancer; Sept. 23-26, 2018; Toronto, Canada.

Antonia SJ, et al. N Eng J Med. 2018;doi:10.1056/NEJMoa1809697.

Disclosures: The study was funded by AstraZeneca. Antonia reports personal fees from AstraZeneca/MedImmune, Boehringer-Ingelheim, Bristol-Myers Squibb, CBMG, FLX Bio, Memgen, Merck and Novartis. Please see the study for all other authors’ relevant financial disclosures.