Meeting NewsPerspective

Durvalumab extends OS in advanced lung cancer

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.

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.

    Perspective
    John Heinzerling

    John Heinzerling

    Antonia and colleagues presented the much-anticipated OS results from the PACIFIC study evaluating the use of durvalumab after chemoradiation for unresectable NSCLC. After published results last year showing a significant improvement in the co-primary endpoint of PFS benefit from 5.6 months to 16.8 months, most expected to see a benefit to OS in this patient group but awaited the publication of the trial’s other primary endpoint.

    Antonia and colleagues presented updated data on OS, PFS and secondary endpoints. With a median follow-up of 25.2 months, there was improvement in 2-year OS from 55.6% to 66.3% with the addition of durvalumab. Median time to death or distant metastasis was also significantly longer with durvalumab, improving from 16.2 months to 28.3 months. Exploratory post-hoc analyses showed benefit of adjuvant durvalumab across tumor types, chemotherapy regimens and PD-L1 status. There also appeared to be benefit in giving immunotherapy within 14 days of completion of chemoradiation.

    The addition of adjuvant immunotherapy after chemoradiation represents the most significant progress in the treatment of locally advanced NSCLC that we have seen in the combined modality era. It appears that there is a benefit to durvalumab across subtypes of NSCLC that persists regardless of PD-L1 expression based on exploratory post-hoc analyses. Thus, in the absence of a contraindication to the drug itself, adjuvant immunotherapy should now be considered standard of care in stage III NSCLC patients who have not progressed after initial chemoradiation. Ongoing trials are continuing to look at whether using other immunotherapy agents, introducing immunotherapy earlier into the treatment regimen for stage III NSCLC, and integrating more aggressive local therapies with immunotherapy can build upon the encouraging results of the PACIFIC study for patients with locally advanced lung cancer.

    • John Heinzerling, MD
    • Levine Cancer Institute
      Atrium Health

    Disclosures: Heinzerling reports no relevant financial disclosures.

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