First-line atezolizumab for patients with NSCLC not eligible for a platinum-containing regimen

IPSOS is the first randomised study to show that first-line treatment with atezolizumab improves overall survival in patients with non-small cell lung cancer who were considered unsuitable for first-line platinum-doublet chemotherapy. This benefit was observed regardless of histology, PD-L1 status and ECOG performance status. In addition, no new safety signals were observed with atezolizumab in this setting and the patients’ quality of life was maintained.

Pivotal clinical trials showed that first-line treatment for non-small cell lung cancer (NSCLC) with immunotherapy, with or without chemotherapy, improved overall survival vs. platinum-doublet chemotherapy. In real-world settings, at least 40% of patients with NSCLC have a poor performance status and/or are elderly with multiple comorbidities and poor tolerance of treatment. Given the relatively poor prognosis and limited treatment options when compared with the significant progress achieved in patients with a good performance status and oncogenic driven NSCLC patients, this population represents an important, under-studied NSCLC group with an unmet medical need to examine the efficacy, safety and quality of life with novel therapeutic options. IPSOS is a phase III, global, multicentre, open-label, randomised, controlled study examining the efficacy, safety and patient-reported outcomes with atezolizumab vs. single-agent chemotherapy who were considered unsuitable for first-line platinum-doublet chemotherapy.

Study design

Patients had locally advanced/metastatic NSCLC without driver mutations and were ineligible for first-line platinum-doublet chemotherapy due to poor performance status (≥2) or comorbidities in patients aged ≥70 years. Patients with EGFR or ALK mutations were excluded from the trial. Patients were randomised 2:1 to atezolizumab 1200 mg IV Q3W or single-agent chemotherapy (vinorelbine or gemcitabine) in 3- or 4-week cycles. The primary endpoint was overall survival (OS). Key secondary endpoints were OS rates, objective response rates (ORR), progression-free survival (PFS), duration of response (DOR) and OS and PFS in PD-L1-positive patients. Safety and health-related quality of life were also assessed.

Results

In total, 453 patients were randomised to atezolizumab (N= 302) or chemotherapy (N= 151). Median age of the patients was 75 years, 31% were ≥80 years, 72% were male and 83% had an ECOG PS ≥2. At data cut-off (30 April 2022), with a median follow-up of 41.0 months, atezolizumab significantly improved OS vs. chemotherapy (stratified HR[95%CI]: 0.78[0.63-0.97], p= 0.028), with a median OS of 10.3 vs. 9.2 months. Two-year OS rates were 24.3% for atezolizumab and 12.4% for chemotherapy. A consistent OS benefit was seen across key subgroups, including PD-L1 expression levels, performance status and histology.

The ORR was 16.9% in the atezolizumab arm, as compared to 7.9% in the chemotherapy arm. Duration of response was nearly double in the atezolizumab arm (14.0 vs. 7.8 months). Median PFS was comparable in the atezolizumab and chemotherapy arms (4.2 vs. 4.0 months, HR[95%CI]: 0.87[0.70-1.07]). Median treatment duration was 3.5 months with atezolizumab, 2.3 months with gemcitabine and 1.8 months with vinorelbine. Despite longer treatment duration, less adverse events were observed in the atezolizumab arm. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 16.3% and 33.3% of patients and Grade 5 TRAEs in 1.0% and 2.7% of patients in the atezolizumab and chemotherapy arms, respectively. AEs leading to study drug discontinuation were reported in approximately 13% of patients in both arms. Atezolizumab improved time to confirmed deterioration of chest pain vs. chemo (HR [95%CI]: 0.51[0.27-0.97); meaningful improvements from baseline were also seen for appetite loss and cough.

Conclusion

First-line atezolizumab significantly improved OS over third generation single-agent chemotherapy in patients with NSCLC deemed ineligible to receive platinum-doublet chemotherapy, regardless of histology, PD-L1 expression and ECOG performance status. The ORR was higher with atezolizumab, with durable responses. In addition, atezolizumab was associated with a stabilisation in HRQoL functioning domains and significant improvement in time to deterioration of chest pain vs. chemotherapy. Finally, no new or unexpected adverse events of special interest were identified with atezolizumab in this study population.

Reference

Lee SM, et al. IPSOS: Results from a Phase 3 study of first-line (1L) atezolizumab (atezo) vs single-agent chemotherapy (chemo) in patients (pts) with NSCLC not eligible for a platinum-containing regimen. Presented at ESMO 2022; Abstract LBA11.