Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 trial

Summary Background Atezolizumab(a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapyas first-line treatment of non-small-cell lung cancer. IMpower130 aimed to assess the efficacy and safety of atezolizumabplus chemotherapyversus chemotherapyalone as first-line therapy for non-squamous non-small-cell lung cancer. Methods IMpower130 was a multicentre, randomised, open-label, phase 3 study done in 131 centres across eight countries (the USA, Canada, Belgium, France, Germany, Italy, Spain, and Israel). Eligible patients were aged 18 years or older, and had histologically or cytologically confirmed stage IV non-squamous non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and received no previous chemotherapyfor stage IV disease. Patients were randomly assigned (2:1; permuted block [ block sizeof six] with an interactive voice or web response system) to receive atezolizumab(1200 mg intravenously every 3 weeks) plus chemotherapy(carboplatin [area under the curve 6 mg/mL per min every 3 weeks] plus nab-paclitaxel[100 mg/m 2 intravenously every week]) or chemotherapyalone for four or six 21-day cycles followed by maintenance therapy. Stratification factors were sex, baseline liver metastases, and PD-L1tumour expression. Co-primary endpoints were investigator-assessed progression-free survival and overall survival in the intention-to-treat wild-type (ie, EGFR wt and ALK wt ) population. The safety population included patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02367781. Findings Between April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumabplus chemotherapygroup (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapygroup (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18·5 months [IQR 15·2–23·6] in the atezolizumabplus chemotherapygroup and 19·2 months [15·4–23·0] in the chemotherapygroup). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18·6 months [95% CI 16·0–21·2] in the atezolizumabplus chemotherapygroup and 13·9 months [12·0–18·7] in the chemotherapygroup; stratified hazard ratio [HR] 0·79 [95% CI 0·64–0·98]; p=0·033) and median progression-free survival (7·0 months [95% CI 6·2–7·3] in the atezolizumabplus chemotherapygroup and 5·5 months [4·4–5·9] in the chemotherapygroup; stratified HR 0·64 [95% CI 0·54–0·77]; p vs 65 [28%] of 232 in the chemotherapygroup), anaemia (138 [29%] vs 47 [20%]), and decreased neutrophil count (57 [12%] vs 19 [8%]). Treatment-related serious adverse events were reported in 112 (24%) of 473 patients in the atezolizumabplus chemotherapygroup and 30 (13%) of 232 patients in the chemotherapygroup. Treatment-related (any treatment) deaths occurred in eight (2%) of 473 patients in the atezolizumabplus chemotherapygroup and one ( Interpretation IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumabplus chemotherapyversus chemotherapyas first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer. Funding F. Hoffmann-La Roche.