Atezolizumab in patients with advanced non-small-cell lung cancer who are platinum-doublet ineligible

Before these inhibitors, 5-year survival rates were 0% for stage IVB disease1 but now approach 20% in those without substantial comorbidities and Eastern Cooperative Oncology Group performance status (ECOG PS) scores of 0 or 1, regardless of PD-L1 expression.2,3 However, this study population and hence outcome does not represent the majority of real-world patients: older people (ie, those 70 years and older), those with substantial comorbidities, frailty, and a poor ECOG PS score, populations that have been routinely excluded from cancer therapeutic trials, for whom rapid registration of novel indications is key, together with risk minimisation. Expert societies and regulatory agencies have recognised this marked disparity between registrational-trial and real-world populations, with the American Society of Clinical Oncology making recommendations to increase the representation of older people and those with comorbidities in trials,5 and the Food and Drug Administration responding with guidelines for the inclusion of older adults in cancer trials.6 In this issue of The Lancet, Siow Ming Lee and colleagues7 present results of the IPSOS trial, the first randomised phase 3 trial of first-line anti-PD-L1 (atezolizumab) versus single-agent chemotherapy in an older population of patients with advanced NSCLC; specifically those with an ECOG PS score of 2 or 3, or those aged 70 years or older with an ECOG PS score of 0 or 1 but with substantial comorbidities or contraindications to platinum-doublet chemotherapy. 453 patients were enrolled and randomised to receive atezolizumab (n=302) or chemotherapy (n=151). The primary outcome measured was overall survival and the trial was positive, showing a significant 22% relative survival benefit for atezolizumab over chemotherapy (stratified hazard ratio 0·78 [95% CI 0·63–0·97], p=0·028), a small median overall survival improvement (10·3 months [95% CI 9·4–11·9] in the atezolizumab group vs 9·2 months [5·9–11·2] in the chemotherapy group), and a doubling of the 2-year survival rate (24% [19·3–29·4] in the atezolizumab group vs 12% [6·7–18·0] in the chemotherapy group), reflecting a later separation of survival curves, typical for these trials, despite more than 50% of their chemotherapy patients who were still alive at 2 years receiving subsequent immunotherapy.