Researchers estimate a 5-year overall survival rate of 42.9% for patients treated with durvalumab compared with 33.4% for those administered a placebo after chemoradiation therapy.
Data presented at the American Society of Clinical Oncology 2021 Annual Meeting showed that treatment with durvalumab (Imfinzi; AstraZeneca) provides a sustained and clinically meaningful overall survival (OS) and progression-free survival (PFS) benefit at 5 years among patients with unresectable, stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiation therapy (CRT).
Durvalumab is a human monoclonal antibody that binds to programmed death-ligand 1 (PD-L1) and inhibits the interaction of PD-L1 with PD-1 and CD80. NSCLC is the most common form of lung cancer, representing approximately 80% to 85% of patients diagnosed. For those with metastatic disease, only 1 in 10 survive 5 years after diagnosis
The randomized, double-blinded, placebo-controlled, multi-center, phase 3 PACIFIC trial evaluated durvalumab in 713 “all-comer” patients, regardless of PD-L1 status, at 235 centers across 26 countries. The trial’s primary endpoints were PFS and OS, with secondary endpoints of landmark PFS and OS, objective response rate, and duration of response.
The findings of the updated post-hoc analyses showed a projected 5-year OS rate of 42.9% for patients treated with durvalumab compared with 33.4% for those administered a placebo after CRT. Median OS was 47.5 months for durvalumab compared with 29.1 months for placebo.
“This trial has once again set a new precedent in the treatment of patients with unresectable, stage III non-small cell lung cancer. Historically, only 15%-30% of these patients survived 5 years, but these results show that with up to 1 year of treatment with Imfinzi, an estimated 43% of patients are still alive at 5 years,” said David Spigel, MD, chief scientific officer at the Sarah Cannon Research Institute, and investigator in the PACIFIC trial, in a press release. “Moreover, three-quarters of these patients had also not progressed in that time. This is a momentous achievement at the 5-year landmark in this curative-intent setting.”
After a maximum treatment course of a year, the study authors estimated that 33.1% of patients treated with durvalumab had not progressed 5 years following enrollment compared to 19% for placebo.
The most common adverse events (AEs)—greater than or equal to 20%—among patients treated with durvalumab compared with placebo were cough (35.2% versus 25.2%); fatigue (24.0% versus 20.5%); dyspnoea (22.3% versus 23.9%); and radiation pneumonitis (20.2% versus 15.8%).
A grade 3 or 4 AE was reported in 30.5% of patients in the durvalumab cohort compared with 26.1% in the placebo group. Further, 15.4% of patients had to discontinue treatment because of AEs associated with durvalumab compared with 9.8% for placebo.
Durvalumab was previously approved by the FDA in the curative-intent setting of unresectable, stage III NSCLC after CRT in the United States. After its initial approval in February 2018, more than 80,000 patients have been treated with durvalumab, according to AstraZeneca.
“Five-year survival is a clinically significant and emotionally meaningful milestone for people with cancer and their families, and it's incredible to see the majority of patients surviving that long have not progressed 4 years after completing treatment,” said Dave Fredrickson, executive vice president, AstraZeneca Oncology Business Unit, in a press release. “These results—the first of their kind in stage III unresectable lung cancer—reinforce the long-term benefit of Imfinzi as the established standard of care in this curative-intent setting.”
Imfinzi demonstrated unprecedented survival in unresectable, Stage III lung cancer with 43% of patients surviving five years. [news release]. June 4, 2021. AstraZeneca. Accessed June 5, 2021.