No abstract

PURPOSE The open-label, phase III POSEIDON study evaluated tremelimumab plus durvalumab and chemotherapy (T + D + CT) and durvalumab plus chemotherapy (D + CT) versus chemotherapy alone (CT) in first-line metastatic non–small-cell lung cancer (mNSCLC). METHODS Patients (n = 1,013) with EGFR/ ALK wild-type mNSCLC were randomly assigned (1:1:1) to tremelimumab 75 mg plus durvalumab 1,500 mg and platinum-based chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression and one additional tremelimumab dose; durvalumab plus chemotherapy for up to four 21-day cycles, followed by durvalumab once every 4 weeks until progression; or chemotherapy for up to six 21-day cycles (with or without maintenance pemetrexed; all arms). Primary end points were progression-free survival (PFS) and overall survival (OS) for D + CT versus CT. Key alpha-controlled secondary end points were PFS and OS for T + D + CT versus CT. RESULTS PFS was significantly improved with D + CT versus CT (hazard ratio [HR], 0.74; 95% CI, 0.62 to 0.89; P = .0009; median, 5.5 v 4.8 months); a trend for improved OS did not reach statistical significance (HR, 0.86; 95% CI, 0.72 to 1.02; P = .0758; median, 13.3 v 11.7 months; 24-month OS, 29.6% v 22.1%). PFS (HR, 0.72; 95% CI, 0.60 to 0.86; P = .0003; median, 6.2 v 4.8 months) and OS (HR, 0.77; 95% CI, 0.65 to 0.92; P = .0030; median, 14.0 v 11.7 months; 24-month OS, 32.9% v 22.1%) were significantly improved with T + D + CT versus CT. Treatment-related adverse events were maximum grade 3/4 in 51.8%, 44.6%, and 44.4% of patients receiving T + D + CT, D + CT, and CT, respectively; 15.5%, 14.1%, and 9.9%, respectively, discontinued treatment because of treatment-related adverse events. CONCLUSION D + CT significantly improved PFS versus CT. A limited course of tremelimumab added to durvalumab and chemotherapy significantly improved OS and PFS versus CT, without meaningful additional tolerability burden, representing a potential new option in first-line mNSCLC.

Results from this open-label trial show that atomoxetine is superior to SCT in addressing broader efficacy and functional outcomes in UK children/adolescents with ADHD. This study contributes to the understanding of broader efficacy in children with ADHD, and is timely in light of recent NICE guidance.

International audienc

In the phase II ATLANTIC study, durvalumab provided durable responses with acceptable tolerability in heavily pretreated patients with advanced NSCLC, across three independent patient cohorts defined by EGFR/ALK status and tumour PD-L1 expression. Preliminary overall survival (OS) data were encouraging. We now report final OS and updated safety data. Methods: Patients with advanced NSCLC with disease progression following ≥2 previous systemic regimens received durvalumab 10 mg/kg every 2 weeks. The primary endpoint was objective response rate among patients with increased PD-L1 expression (defined as ≥25 % or ≥90 % of tumour cells [TCs], cohort-dependent). Secondary endpoints included OS and safety. Results: 444 patients received durvalumab: 111 in Cohort 1 (EGFR+/ALK+), 265 in Cohort 2 (EGFR−/ALK−), and 68 in Cohort 3 (EGFR−/ALK−; TC ≥ 90 %). Median (95 % CI) OS was 13.3 months (6.3-24.5) in patients with EGFR+/ALK+ NSCLC with TC ≥ 25 %, 10.9 months (8.6-13.6) in patients with EGFR-/ALK-NSCLC with TC ≥ 25 %, and 13.2 months (5.9-not reached) in patients with EGFR-/ALK-NSCLC with TC ≥ 90 %. Median (95 % CI) OS was slightly shorter in patients with TC < 25 % (9.9 months [4.2-13.3] in patients with EGFR +/ALK+ NSCLC and 9.3 months [5.9-10.8] in those with EGFR-/ALK-NSCLC). Treatment-related adverse events of special interest occurred with similar incidences as reported previously. Conclusions: After additional follow-up, final OS data remain encouraging across all cohorts, further supporting the clinical activity of durvalumab in patients with heavily pretreated advanced NSCLC, including those with EGFR+/ALK+ tumours. There were no new safety signals.