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Durvalumab extends PFS in stage III lung cancer
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MADRID — Durvalumab significantly extended PFS compared with placebo among patients with locally advanced, unresectable stage III lung cancer, according to interim results of the phase 3 PACIFIC trial presented at the European Society for Medical Oncology Congress.
Researchers observed consistent benefit among all analyzed subgroups.
Durvalumab (Imfinzi, AstraZeneca), a PD-L1 inhibitor, also appeared well tolerated. The results suggest the agent could be a promising therapy for this patient population, Luis Paz-Ares, MD, chair of the medical oncology department at Hospital Universitario Doce de Octubre in Madrid, told HemOnc Today.
“This is a very robust and clinically significant improvement for patients,” Paz-Ares said. “The benefit is very clear.”
An estimated one-third of patients with non-small cell lung cancer present with stage III disease. Standard treatment — which consists of platinum-based chemotherapy and concurrent radiation therapy — typically confers PFS of approximately 8 months. However, most patients progress, and only 15% of patients survive 5 years.
Prior research revealed a synergy between radiotherapy and immunotherapy that may increase likelihood of response.
The global double-blind, placebo-controlled PACIFIC trial — results of which were published simultaneously in The New England Journal of Medicine — was the first phase 3 trial to assess an immune checkpoint inhibitor as sequential treatment for patients with stage III NSCLC who did not progress after concurrent platinum-based chemotherapy and radiation therapy.
The trial — conducted at 235 centers in 26 countries — included 709 patients with WHO performance status of 0 or 1 who received at least two cycles of platinum-based chemoradiation therapy. Patients were enrolled regardless of PD-L1 status.
Researchers randomly assigned 473 patients to durvalumab (Imfinzi, AstraZeneca) 10 mg/kg via IV every 2 weeks. The other 236 patients received placebo. Treatment continued for up to 1 year.
PFS by blinded independent central review and OS served as coprimary endpoints. PFS rates at 12 and 18 months, objective response rate, duration of response, time to death or distant metastasis, and safety served as secondary endpoints.
Median follow-up was 14.5 months.
Durvalumab-treated patients achieved significantly longer median PFS (16.8 months vs. 5.6 months; HR = 0.52; 95% CI, 0.42-0.65). Researchers also reported higher 12-month PFS (55.9% vs. 35.3%), 18-month PFS (44.2% vs. 27%) and ORR (28.4% vs. 16%; P < .001) in the durvalumab group. Median time to death or distant metastasis also was longer among durvalumab-treated patients (23.2 months vs. 14.6 months; stratified HR = 0.52; 95% CI, 0.39-0.69).
OS data had not matured by the time of interim PFS analysis.
Durvalumab-treated patients experienced higher incidence of treatment-related adverse events (68% vs. 53%) and immune-mediated adverse events (24% vs. 8%).
However, incidence of severe toxicity appeared similar between groups. Researchers reported comparable rates of grade 3/grade 4 adverse events (32% for durvalumab vs. 27.8% for placebo), the most common of which was pneumonia (4.4% vs. 4.3%). A higher percentage of durvalumab-treated patients discontinued treatment due to adverse events (15.4% vs. 9.8%).
“The safety profile of durvalumab was consistent with that of other immunotherapies, and with its known safety profile as monotherapy in patients with more advanced disease,” Paz-Ares said during a press conference. “No new safety signals were identified.”
Results of the interim analysis suggest PD-L1 inhibition after chemoradiation can be a viable option patients with locally advanced, unresectable stage III lung cancer, according to Pilar Garrido, MD, head of the thoracic tumor section in the medical oncology department at Ramon y Cajal University Hospital in Madrid, said in an ESMO-issued press release.
She described the PFS benefit as “clinically relevant” and suggested improvements in 12-month and 18-month PFS are “highly encouraging.” She also emphasized durvalumab’s acceptable toxicity profile.
“Overall survival data are awaited, but the magnitude of progression-free survival benefit supports this combination as a new standard of care for unresectable stage III NSCLC patients who had no progression following standard care with platinum-based chemotherapy and concomitant radiotherapy,” Garrido said. “Further research is needed regarding the duration and timing of immunotherapy, the best regimen of chemoradiation to combine with it, and the selection of patients most likely to benefit based on predictive biomarkers.” – by Mark Leiser
Reference:
Paz-Ares L, et al. Abstract LBA1_PR. Presented at: European Society for Medical Oncology Congress; Sept. 8-12, 2017; Madrid.
Antonia SJ, et al. N Engl J Med. 2017;doi: 10.1056/NEJMoa1709937.
Disclosures: Astra Zeneca funded this study. Paz-Ares reports consultant fees from AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche, Eli Lilly, Boehringer Ingelheim, Novartis and Ariad. Please see the abstract for a list of all other researchers’ relevant financial disclosures.