The immune checkpoint inhibitor durvalumab may be safe and effective at improving overall survival in patients who have advanced or metastatic non–small cell lung cancer (NSCLC) and borderline performance status, according to a recent study published by Shaverdashvili et al in eClinicalMedicine.
Background
Lung cancer is the deadliest cancer type, causing over 125,000 deaths in the United States per year. When NSCLC, which makes up about 85% of all lung cancer cases, progresses to the advanced or metastatic stage, the rate of survival decreases.
“Over the last decade, the development of immunotherapies has revolutionized treatment for NSCLC and greatly improved survival outcomes,” explained senior study author Liza Villaruz, MD, Associate Professor of Medicine at the University of Pittsburgh and Co-Leader of the Immunotherapy and Drug Development Center at the University of Pittsburgh Medical Center Hillman Cancer Center. “However, there is a paucity of data to support the safety and efficacy of these agents in patients with borderline performance status,” she noted.
Previous studies have shown that about 33% of patients with advanced or metastatic NSCLC may have borderline Eastern Cooperative Oncology Group (ECOG) performance status. Nonetheless, since many clinical trials for cancer drugs limit eligibility to patients with lower ECOG scores of 0 or 1, those with borderline scores of 2 or above may be underrepresented.
“Clinical trials for drug approvals have very selective eligibility criteria, so there is concern that study patient populations don’t always reflect the real world,” stressed Dr. Villaruz. “A strength of our study is that it was done across community-based clinics in rural and underserved areas in patients with limited performance status, so this is a real-world patient population,” she added.
Durvalumab was designed to block the activity of immune-suppressing PD-L1 proteins and help the immune system target cancer cells. The drug has received U.S. Food and Drug Administration approval as postremission therapy following treatment with chemoradiation in advanced and metastatic NSCLC; however, the trial that led to its approval involved only patients with lower ECOG scores.
Study Methods and Results
In the new single-arm phase II trial, researchers examined the safety and efficacy of first-line intravenous durvalumab administered every 28 days for up to 12 months in 50 patients with stage IIIB or IV NSCLC and ECOG scores of 2. The physicians also assigned the patients to undergo testing to measure the proportion of their tumor cells expressing PD-L1 in order to predict treatment efficacy.
The researchers found that the median overall survival was 6 months in the patients with PD-L1–negative tumors and 11 months in those with PD-L1–positive tumors. The patients’ health-related quality of life remained statistically similar between baseline and over the course of treatment, and severe treatment-related adverse events occurred in only 19% of the patients.
In comparison, the researchers emphasized that patients receiving platinum doublet chemotherapy, the standard-of-care first-line therapy for advanced NSCLC, have an overall survival of about 9 months and 30% of the patients with borderline performance status experience severe treatment-related adverse events.
Conclusions
“Although our study did not have a control group, the findings suggest that durvalumab has a survival benefit for [patients with] NSCLC [who have] PD-L1–positive tumors and borderline performance status. Importantly, it gives us reassurance that durvalumab is safe, well-tolerated, and is associated with stable quality of life,” underscored Dr. Villaruz.
“We show that it’s feasible to conduct clinical trials with medically complex patients who may not be able to travel to large academic hubs. The ability to do clinical research within that patient population at rural cancer sites is important for improving representation within clinical trial findings,” she concluded.
Disclosure: The research in this study was supported by the National Cancer Institute and AstraZeneca. For full disclosures of the study authors, visit thelancet.com.
