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Background Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. MethodsThe Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. Findings Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68•0 years (61•8-75•0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1•88, 95% 1•00-3•62), being a current or former smoker (4•24, 1•70-12•95), receiving treatment with chemotherapy alone (2•54, 1•09-6•11), and the presence of any comorbidities (2•65, 1•09-7•46) were associated with increased risk of death. However, in multivariable analysis, only smo...

PURPOSE In KEYNOTE-189, first-line pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) compared with placebo plus pemetrexed-platinum in patients with metastatic nonsquamous non‒small-cell lung cancer (NSCLC), irrespective of tumor programmed death-ligand 1 (PD-L1) expression. We report an updated analysis from KEYNOTE-189 (ClinicalTrials.gov: NCT02578680 ). METHODS Patients were randomly assigned (2:1) to receive pemetrexed and platinum plus pembrolizumab (n = 410) or placebo (n = 206) every 3 weeks for 4 cycles, then pemetrexed maintenance plus pembrolizumab or placebo for up to a total of 35 cycles. Eligible patients with disease progression in the placebo-combination group could cross over to pembrolizumab monotherapy. Response was assessed per RECIST (version 1.1) by central review. No alpha was assigned to this updated analysis. RESULTS As of September 21, 2018 (median follow-up, 23.1 months), the updated median (95% CI) OS was 22.0 (19.5 to 25.2) months in the pembrolizumab-combination group versus 10.7 (8.7 to 13.6) months in the placebo-combination group (hazard ratio [HR], 0.56; 95% CI, 0.45 to 0.70]). Median (95% CI) PFS was 9.0 (8.1 to 9.9) months and 4.9 (4.7 to 5.5) months, respectively (HR, 0.48; 95% CI, 0.40 to 0.58). Median (95% CI) time from randomization to objective tumor progression on next-line treatment or death from any cause, whichever occurred first (progression-free-survival-2; PFS-2) was 17.0 (15.1 to 19.4) months and 9.0 (7.6 to 10.4) months, respectively (HR, 0.49; 95% CI, 0.40 to 0.59). OS and PFS benefits with pembrolizumab were observed regardless of PD-L1 expression or presence of liver/brain metastases. Incidence of grade 3-5 adverse events was similar in the pembrolizumab-combination (71.9%) and placebo-combination (66.8%) groups. CONCLUSION First-line pembrolizumab plus pemetrexed-platinum continued to demonstrate substantially improved OS and PFS in metastatic nonsquamous NSCLC, regardless of PD-L1 expression or liver/brain metastases, with manageable safety and tolerability.

BACKGROUND: Approved systemic treatments for malignant pleural mesothelioma (MPM) were limited to chemotherapy regimens that have moderate survival benefit with poor outcomes. Nivolumab plus ipilimumab showed clinical benefit in other tumour types, including first-line non-small cell lung cancer. We hypothesised that this regimen would improve overall survival in MPM. METHODS:This open-label phase 3 study was conducted at 103 hospitals across 21 countries. Adults with previously untreated, histologically confirmed unresectable MPM were randomised (1:1) to nivolumab (3 mg/kg intravenously Q2W) plus ipilimumab (1 mg/kg intravenously Q6W) for ≤2 years, or platinum plus pemetrexed chemotherapy (pemetrexed [500 mg/m 2 intravenously] plus cisplatin [75 mg/m 2 intravenously] or carboplatin [AUC 5 mg/mL/min intravenously]) Q3W for up to 6 cycles. The primary endpoint was overall survival (all randomised patients); safety was assessed in all treated patients. This study is registered with ClinicalTrials.gov, NCT02899299. FINDINGS:Between November 29, 2016 and April 18, 2018, 713 patients were enrolled; 303 were randomised to nivolumab plus ipilimumab and 302 to chemotherapy. At the prespecified interim analysis (median follow-up 29•7 months [IQR,[26][27][28][29][30][31][32]), nivolumab plus ipilimumab significantly prolonged overall survival versus chemotherapy. Median overall survival was 18•1 months (95% CI 16•8-21•4) versus 14•1 months (95% CI 12•4-16•2), with a hazard ratio of 0•74 (96•6% CI 0•60-0•91; p=0•0020); 2year overall survival rates were 41% (95% CI 35•1-46•5) and 27% (95% CI 21•9-32•4), respectively.Grade 3-4 treatment-related adverse events were reported in 91 (30%) of 300 patients treated with nivolumab plus ipilimumab and 91 (32%) of 284 treated with chemotherapy. There were three (1%) and one (<1%) treatment-related deaths, respectively. INTERPRETATION:Nivolumab plus ipilimumab provided statistically significant and clinically meaningful improvements in overall survival versus standard-of-care chemotherapy, supporting the use of this first-in-class approved (United States) regimen for previously untreated unresectable MPM.

PURPOSE This phase III, multicenter, randomized, placebo-controlled trial assessed the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel in chemotherapy-naïve patients with unresectable stage IIIB or IV non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS Nine hundred twenty-six patients were randomly assigned to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m(2) (CP) on day 1, followed by either sorafenib 400 mg twice a day (n = 464, arm A) or placebo (n = 462, arm B) on days 2 to 19. The maintenance phase after CP consisted of sorafenib 400 mg or placebo twice a day. The primary end point was overall survival (OS); secondary end points included progression-free survival and tumor response. RESULTS Overall demographics were balanced between arms; 223 patients (24%) had squamous cell histology. On the basis of a planned interim analysis, median OS was 10.7 months in arm A and 10.6 months in arm B (hazard ratio [HR] = 1.15; 95% CI, 0.94 to 1.41; P = .915). The study was terminated after the interim analysis concluded that the study was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality in arm A than in arm B (HR = 1.85; 95% CI, 1.22 to 2.81). Main grade 3 or 4 sorafenib-related toxicities included rash (8.4%), hand-foot skin reaction (7.8%), and diarrhea (3.5%). CONCLUSION No clinical benefit was observed from adding sorafenib to CP chemotherapy as first-line treatment for NSCLC.