ImportanceProgrammed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.ObjectiveTo evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.Design, Setting, and ParticipantsThis international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.InterventionsPatients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.Main Outcomes and MeasuresThe primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P < .012). There were 13 secondary outcomes, including progression-free survival and adverse events.ResultsAmong the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2-24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months-not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0-14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49-0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5-6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2-4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38-0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.Conclusions and RelevanceAmong patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT04063163

BackgroundTo compare the efficacy of crizotinib, pemetrexed and other chemotherapy regimens as a first-line treatment in patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in real world clinical use and to evaluate the +86–571-87,236,876 predictive clinical factors of the efficacy of crizotinib.MethodsThe 73 patients with ALK-positive advanced NSCLC were divided into three groups based on the first-line treatment: first-line crizotinib group (1-CRZ group, n = 32); first-line platinum-based pemetrexed treatment group (1-PP group, n = 28), and first-line chemotherapy platinum-based non-pemetrexed group (N1-PP, n = 12). Sixty eight of the 73 patients received crizotinib treatment and followed up in our hospital. Differences in the objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) were compared in the different groups. The clinical factors were evaluated to predict the efficacy of crizotinib by the Kaplan–Meier survival analysis and Cox proportional hazards model.ResultsThe PFS, ORR, DCR were 16.1 months, 78.1% (25/32) and 100% (32/32) in the 1-CRZ group; were 6.0 months, 17.9% (5/28) and 57.2% (16/28) in the 1-PP group; and were 2.9 months, 15.4% (2/13) and 46.2% (6/13) in the N1-PP group. The PFS of the 1-CRZ group was significantly longer than that of the 1-PP group (P < 0.001) and the N1-PP group (P < 0.001). The ORR and DCR of the 1-CRZ group was significantly greater than that of the 1-PP group and the N1-PP group (all the P < 0.001). Higher Eastern Cooperative Oncology Group (ECOG) performance status score (> = 2) (HR 2.345, 95% CI 1.137–4.834, P = 0.021) and patients received crizotinib after N1-PP chemotherapy (HR 2.345, 95% CI 1.137–4.834, P = 0.021) were two factors associated with shorter PFS after crizotinib treatment.ConclusionsIn patients with ALK-positive NSCLC who did not receive previous treatment, crizotinib was superior to standard chemotherapy for the longer PFS and greater ORR and DCR. Higher ECOG score (> = 2) and patients received crizotinib after N1-PP chemotherapy predict poor efficacy of crizotinib.

A novel lateral-flow device (LFD) has been invented for use as a diagnostic tool for invasive aspergillosis (IA). We conducted a meta-analysis to assess the diagnostic accuracy of the device. Published studies that used the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria and provided sufficient data were included. Two reviewers independently collected the data from each study and assessed the risk bias using the Quality Assessment of Diagnostic Accuracy Studies-2. The pooled sensitivity, specificity and diagnostic odds ratio (DOR) were computed and reported with a 95 % confidence interval 90 (95 % CI,) in the LFD test using serum. We concluded that the Aspergillus LFD had a good diagnostic value in immunocompromised patients at risk of IA. The BAL LFD might have a better performance than the serum LFD test.

8505 Background: Monoclonal antibodies against programmed death-ligand 1 (PD-L1) have been approved for the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) in combination with chemotherapy. However, whether a programmed death 1 (PD-1) inhibitor provides similar survival benefit in this patient population remains unclear. In this study, the efficacy and safety of serplulimab, a novel humanized monoclonal anti-PD-1 antibody, were assessed in combination with chemotherapy in previously untreated ES-SCLC patients. Methods: In this international, randomized, double-blind, multicenter, phase 3 trial (NCT04063163), patients with ES-SCLC who had not received prior systemic therapy were randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 4 cycles. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results: Between September 12, 2019 and April 27, 2021, 585 patients were randomized (serplulimab group, n = 389; placebo group, n = 196). At interim analysis, the median follow-up duration was 12.3 months. Median OS was significantly prolonged in the serplulimab group than the placebo group (15.4 vs.10.9 months; hazard ratio [HR] 0.63, 95% CI 0.49–0.82; P < 0.001). Median PFS assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was significantly longer in the serplulimab group than the placebo group (5.8 vs. 4.3 months; HR 0.47, 95% CI 0.38–0.59; P < 0.001). Efficacy improvements were also observed in ORR (80.2% vs. 70.4%) and DoR (5.6 vs. 3.2 months) as assessed by IRRC per RECIST v1.1. Grade ≥3 treatment-emergent adverse events (TEAEs) related to serplulimab or placebo were reported in 129 (33.2%) and 54 (27.6%) patients in the respective groups. Incidence of immune-related TEAEs was higher in the serplulimab group compared to the placebo group (37% vs. 18.4%), with the largest difference in endocrine disorders (18.3% vs. 4.6%), which are commonly reported with anti-PD-1/PD-L1 therapies. Four deaths (1 acute coronary syndrome, 1 pyrexia, and 1 platelet count decreased in the serplulimab group; 1 thrombocytopenia in the placebo group) that might be related to study drugs were reported. Conclusions: Serplulimab plus chemotherapy as first-line treatment provided significant benefits and a manageable safety profile compared with chemotherapy alone in ES-SCLC patients. For the first time, OS benefits was demonstrated with a PD-1 inhibitor in a global phase 3 study among previously untreated ES-SCLC patients. Clinical trial information: NCT04063163.

The 5-day regimen of levofloxacin 750 mg daily is non-inferior to 7-14-day conventional regimen of 500 mg daily in clinical efficacy for treatment of mild to moderate Chinese CAP population. The short course regimen allows the reduction of antimicrobial drug exposure and is well tolerated.