Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

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Background: Concurrent chemotherapy and thoracic radiotherapy (CRT) followed by prophylactic cranial irradiation (PCI) is the standard strategy in limited stage small cell lung cancer (LS-SCLC).Methods: STIMULI is a 1:1 randomized phase II international trial aiming to demonstrate superiority of consolidation immunotherapy treatment (C) vs observation (O) after standard CRT and PCI, in patients (pts) with LS-SCLC. C consisted of four cycles of nivolumab (1 mg/kg, Q3W) plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months (m). The trial was designed to test two co-primary endpoints, progression-free survival (PFS) by RECIST 1.1 criteria, and overall survival (OS), at 1-sided alpha of 1% and 4%, respectively. Trial enrollment closed prematurely due to slow accrual, after half the initial sample size. The statistical analyses plan was updated to address PFS as primary endpoint to be tested at the full 5% 1-sided significance level. 81 PFS events were needed to achieve a power of 80% for testing an HR of 0.57. Secondary endpoints include OS, time to treatment failure (TTF), and safety.Results: 222 pts were enrolled with 153 randomized after completion of CRT and PCI, 78 to C and 75 to O. Median age 62 years, 60% males, 34%/65% current/former smokers, 31%/66% ECOG PS 0/1. In C, 40 PFS events were observed, with median PFS 10.7 m (95% CI 7.0-Not Estimable (NE)) vs 42 events and median 14.5 m (8.2-NE) in O, HR¼1.02 (0.66-1.58), 2-sided p¼0.93. Two-year PFS rate was 43% (31-55) and 40% (28-52) in C and O respectively. Median OS was not reached in C, while it was 31.6 m (26.1-NE) in O, HR¼1.06 (0.61-1.86), p¼0.83. One-year OS rate was 79% (68-87) in C and 89% (78-94) in O. Exploratory subgroups will be presented. In C, median time to treatment discontinuation was only 1.7 m. Grade!3 AEs were experienced by 62% pts in C and 25% in O, with 4 and 1 fatal AE, respectively.Conclusions: PFS for LS-SCLC pts is not found different between C and O, possibly due to the short period on active treatment observed in the study. Clinical trial identification: NCT02046733.Legal entity responsible for the study: European Thoracic Oncology Platform (ETOP).

Introduction: Recurrent venous thromboembolism (VTE) despite curative anticoagulation is frequent in patients with cancer. Identifying patients with a high risk of recurrence could have therapeutic implications. A prospective study was designed to validate the Ottawa risk score of recurrent VTE in cancer patients. Methods: In a prospective multicenter observational cohort, adult cancer patients with a recent diagnosis of symptomatic or incidental lower limb deep vein thrombosis or pulmonary embolism were treated with tinzaparin for 6 months. The primary endpoint was the recurrence of symptomatic or asymptomatic VTE within the first 6 months of treatment. All clinical events were centrally reviewed and adjudicated. Time-to-event outcomes were estimated by the Kalbfleisch and Prentice method to take into account the competing risk of death. A C-statistic value >0.70 was needed to validate the Ottawa score. Results: A total of 409 patients were included and analyzed on an intention-to-treat basis. Median age was 68 years, 60.4% of patients had PE, VTE was symptomatic in 271 patients (66.3%). The main primary sites were lung (31.3%), digestive tract (18.3%) and breast (13.9%) cancers. The Ottawa score was high (≥1) in 58% of patients. The 6-month cumulative incidence of recurrent VTE was 7.3% (95% confidence interval [CI]: 4.9-11.1) overall, and 5.0% (95%CI: 2.3-10.8) vs 9.1% (95%CI: 6.1-13.6) in the Ottawa low vs high risk groups, respectively. The C-statistic value was 0.60 (95%CI: 0.55-0.65). Conclusion: In this prospective cohort of patients with cancer receiving tinzaparin for VTE, the Ottawa score failed to accurately predict recurrent VTE.

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5500 Background: To investigate whether adding Pembrolizumab (P) to neoadjuvant carboplatin-paclitaxel chemotherapy (CP) may increase the optimal debulking rate, assessed by Complete Resection Rate (CRR) after Interval Debulking Surgery (IDS) in patients (pts) with initially unresectable International Federation of Gynecology and Obstetrics (FIGO) stage IIIC/IV ovarian, tubal or peritoneal HGSC. Methods: Multicenter, open-label, non-comparative randomized phase II trial. Pts were randomized (2:1) to receive 4 cycles of CP ± P before IDS. After IDS, all patients received post-operative chemotherapy (2 to 4 cycles) and optional bevacizumab for 15 months in total ± P as maintenance therapy for up to 2 years. Randomization was stratified on center, FIGO stage, Bev planned after IDS and disease volume (<5cm/>5cm). Primary endpoint was the centrally reviewed CRR at IDS. 60 pts were planned in the CP+P arm (A'Hern's single-stage design P0=50%, P1=70%). Safety (particularly due to P addition), surgical morbidity, ORR, PFS and OS were secondary endpoints. Results: 91 pts were randomized from 02/18 to 04/19 with a median Peritoneal Cancer Index at 24 (range 7-39). 80 pts (88%) received Bev in combination with CP followed by bev ± P in maintenance. In the CP+P group (n=61), 58 (95%) pts had IDS and 78% achieved complete resection. The CRR in this group was 74%, statistically superior to the pre-defined hypothesis. In the CP group, CRR was 70% (29/30 pts underwent IDS). Complete resection after strictly 4 cycles of CP±P was obtained for 41 pts (71%) and 17 (58%) pts in CP+P and CP group, respectively (sensitivity analysis). For CP+P group, numerically higher ORRs were observed before IDS compared to CP group (76% vs 61%). Grade ≥3 adverse events (AE) occurred in 75% of the CP+P group and 67% in the CP group: mainly blood and lymphatic, gastrointestinal and vascular disorders. Postoperative AE (mainly infectious, vascular and gastrointestinal) occurred in 20% and 13% of the pts in CP+P and CP arm, respectively. No difference in the number of fatal events between the two arms: 2 in the experimental arm vs 1 in the control arm. Progression free survival rate at 18 months was 61% (95CI% [47-73]) and 57% (95CI% [37-72]) in CP+P and CP arm, respectively. Conclusions: P may be safely added to preoperative treatment in pts deemed non-optimally resectable. The primary objective was met with an improved CRR on CP+P arm. The CRR in the control group was higher than expected. Survival data and translational research including PDL1 status are ongoing to better define P as treatment option in this setting. Clinical trial information: 2016-004-163-39. Clinical trial information: NCT03275506.