Atezolizumab in Combination With Carboplatin and Nab-Paclitaxel in Advanced Squamous NSCLC (IMpower131): Results From a Randomized Phase III Trial

Introduction: Cytotoxic agents have immunomodulatory effects, providing a rationale for combining atezolizumab (anti-programmed death-ligand 1 [anti–PD-L1]) with chemotherapy. The randomized phase III IMpower131 study (NCT02367794) evaluated atezolizumab with platinum-based chemotherapy in stage IV squamous NSCLC. Methods: A total of 1021 patients were randomized 1:1:1 to receive atezolizumabþcarboplatinþpaclitaxel (AþCP) (n ¼ 338), atezolizumabþcarboplatinþnab-paclitaxel (AþCnP) (n ¼ 343), or carboplatinþnab-paclitaxel (CnP) (n ¼ 340) for four or six 21-day cycles; patients randomized to the AþCP or AþCnP arms received atezolizumab maintenance therapy until progressive disease or loss of clinical benefit. The coprimary end points were investigatorassessed progression-free survival (PFS) and overall survival (OS) in the intention-to-treat (ITT) population. The secondary end points included PFS and OS in PD-L1 subgroups and safety. The primary PFS (January 22, 2018) and final OS (October 3, 2018) for AþCnP versus CnP are reported. Results: PFS improvement with AþCnP versus CnP was seen in the ITT population (median, 6.3 versus 5.6 mo; hazard ratio [HR] ¼ 0.71, 95% confidence interval [CI]: 0.60–0.85; p ¼ 0.0001). Median OS in the ITT population was 14.2 and 13.5 months in the AþCnP and CnP arms (HR ¼ 0.88, 95% CI: 0.73–1.05; p ¼ 0.16), not reaching statistical significance. OS improvement with AþCnP versus CnP was observed in the PD-L1–high subgroup (HR ¼ 0.48, 95% CI: 0.29–0.81), despite not being formally tested. Treatment-related grade 3 and 4 adverse events and serious adverse events occurred in 68.0% and 47.9% (AþCnP) and 57.5% and 28.7% (CnP) of patients, respectively. Conclusions: Adding atezolizumab to platinum-based chemotherapy significantly improved PFS in patients with first-line squamous NSCLC; OS was similar between the arms

Genetic studies of human diversity in East Asia

East Asia is one of the most important regions for studying evolution and genetic diversity of human populations. Recognizing the relevance of characterizing the genetic diversity and structure of East Asian populations for understanding their genetic history and designing and interpreting genetic studies of human diseases, in recent years researchers in China have made substantial efforts to collect samples and generate data especially for markers on Y chromosomes and mtDNA. The hallmark of these efforts is the discovery and confirmation of consistent distinction between northern and southern East Asian populations at genetic markers across the genome. With the confirmation of an African origin for East Asian populations and the observation of a dominating impact of the gene flow entering East Asia from the south in early human settlement, interpretation of the north–south division in this context poses the challenge to the field. Other areas of interest that have been studied include the gene flow between East Asia and its neighbouring regions (i.e. Central Asia, the Sub-continent, America and the Pacific Islands), the origin of Sino-Tibetan populations and expansion of the Chinese