In the phase III IPSOS trial reported in The Lancet, Lee et al found that first-line atezolizumab improved overall survival vs single-agent chemotherapy in patients with advanced non–small cell lung cancer (NSCLC) who were ineligible for platinum-based chemotherapy.
Study Details
In the open-label trial, 453 patients with stage IIIB to IV NSCLC from sites in Asia, Europe, North America, and South America were randomly assigned 2:1 between September 2017 and September 2019 to receive atezolizumab at 200 mg every 3 weeks (n = 302) or investigator’s choice of single-agent vinorelbine or gemcitabine in 3- or 4-week cycles (n = 151). Patients were considered ineligible for platinum-based chemotherapy on the basis of Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3, or age ≥ 70 years with ECOG PS of 0 or 1 with substantial comorbidities or contraindications for platinum doublets. The primary endpoint was overall survival in the intention-to-treat population.
Overall Survival
Median follow-up was 41.0 months (interquartile range [IQR] = 36.7–47.8 months). Median patient age was 75 years (IQR = 69.0–80.0 years) and 140 patients (31%) were aged ≥ 80 years; 83% of patients had an ECOG performance status of 2 or 3.
Median overall survival was 10.3 months (95% confidence interval [CI] = 9.4–11.9 months) in the atezolizumab group vs 9.2 months (95% CI = 5.9–11.2 months) in the chemotherapy group (stratified hazard ratio [HR] = 0.78, 95% CI = 0.63–0.97, P = .028). Rates were 64% vs 58% at 6 months, 44% vs 39% at 12 months, 31% vs 24% at 18 months, and 24% vs 12% at 24 months.
Median progression-free survival was 4.2 months (95% CI = 3.7–5.5 months) in the atezolizumab group vs 4.0 months (95% CI = 2.9–5.4 months) in the chemotherapy group (stratified HR = 0.87, 95% CI = 0.70–1.07), with 12- and 24-month rates of 20% vs 14% and 9% vs 2%, respectively. Subsequent anticancer therapies were received by 20% of patients in the atezolizumab group (chemotherapy in 16%) and 30% of the chemotherapy group (immunotherapy in 19%). Among patients in the chemotherapy group, 21 (40%) of 52 who were alive at 1 year and 9 (56%) of 16 alive at 2 years had received subsequent immunotherapy.
Adverse Events
Treatment-related grade 3 or 4 adverse events occurred in 16% of patients in the atezolizumab group vs 33% of the chemotherapy group. Serious treatment-related adverse events occurred in 12% vs 16% of patients; adverse events led to discontinuation of treatment in 13% vs 14%. Treatment-related death occurred in three patients (1%) vs four patients (3%). Compared with the chemotherapy group, the atezolizumab group exhibited stabilization or improvement in patient-reported health-related quality-of-life functioning scales and symptoms.
The investigators concluded, “First-line treatment with atezolizumab monotherapy was associated with improved overall survival, a doubling of the 2-year survival rate, maintenance of quality of life, and a favorable safety profile compared with single-agent chemotherapy. These data support atezolizumab monotherapy as a potential first-line treatment option for patients with advanced NSCLC who are ineligible for platinum-based chemotherapy.”
Siow Ming Lee, FRCP, of the Department of Oncology, UCLH NHS Foundation Trust, London, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann-La Roche and Genentech Inc, a member of the Roche group. For full disclosures of the study authors, visit thelancet.com.
