Intrapleural nivolumab in cancer patients with pleural effusion.

ABSTRACT: We assessed the preliminary efficacy and toxicity of intrapleural instillation of nivolumab in patients with large pleural effusion. Patients with metastatic cancers who have a large volume of pleural effusion and required evacuation were eligible. Thoracentesis followed by nivolumab (40 mg, single intrapleural instillation) was performed. The primary endpoint was 3-month recurrence-free survival. A total of 13 patients were enrolled. The study was terminated after stage 1 as no efficacy was observed; 7 patients (54%) had a recurrence of pleural effusion at 3 months. Thirteen (100%) patients had no recurrence, dyspnea, or cough within 1 month, and the median time to recurrence was 1.9 months (95% confidence interval [CI], 1.35-2.5). No adverse events were identified. We concluded that a single intrapleural instillation of the nivolumab at 40 mg was ineffective and well-tolerated in cancer patients with pleural effusion.

Multicenter phase 2 study of intrapleural nivolumab in patients with metastatic non-small cell lung cancer and pleural effusion.

About 40% of patients with non-small cell lung cancer (NSCLC) developed pleural effusions at some time during the course of their disease. Preliminary results from our Phase 2 multicentre clinical trial (Cohort 1) demonstrated the safety of intrapleural nivolumab in cancer patients. In Cohort 2 we assessed the preliminary efficacy and toxicity of intrapleural instillation of the nivolumab in patients with metastatic NSCLC and large pleural effusion requiring evacuation. Thoracentesis followed by nivolumab (40 mg, single intrapleural instillation) was performed. The primary endpoint was 3-month recurrence-free survival. Simon's two-stage design was used, with 13 patients planned for stage 1. If 11 or more patients did not have a pleural effusion after 3 months, an additional 35 patients were planned to be accrued for a total of 48. A total of 13 patients were enrolled. This study did not meet its primary endpoint and was terminated. Eight patients (61.5%) had a recurrence of pleural effusion at 3 months. The median time to recurrence was 1.84 months (95% CI 1.19-2.49). No adverse events were identified. We concluded that a single intrapleural instillation of the nivolumab at 40 mg was ineffective and well-tolerated in patients with metastatic NSCLC and pleural effusion.

Safety and preliminary efficacy of the Gam-COVID-Vac vaccine and outcomes of SARS-CoV-2 infection in Russian patients with genitourinary malignancies.

BACKGROUND: To our knowledge, there is no clinical data pertaining to COVID-19 outcomes and safety of COVID-19 vaccination in Russian patients with genitourinary (GU) malignancies. Aim of our analysis was to describe the characteristics of the COVID-19 infection course as well as preliminary safety and efficacy of Gam-COVID-Vac vaccine in patients with active GU malignancies. METHODS: Patients were retrospectively identified at nine cancer centers in different regions. Patients were included if COVID-19 was diagnosed by a polymerase chain reaction. Data from additional patients with GU cancers who had no positive SARS-CoV-2 RT-PCR test before vaccination and who received two doses of Gam-COVID-Vac (Sputnik V) between 11 February and 31 August 2021 were collected for safety assessment. Anonymized data were collected through an online registry covering demographics, treatments, and outcomes. RESULTS: The Gam-COVID-Vac vaccine was well tolerated; no grade 3-5 toxicities were reported in 112 vaccinated metastatic GU cancer patients. The most common grade 1 adverse events (81%) were injection site reactions (76%), flu-like illness (68%), and asthenia (49%). Five patients experienced grade 2 chills (4.5%) and 3 patients had grade 2 fever (2.7%). With median follow-up of 6.2 months, two COVID-19 cases were confirmed by RT-PCR test in the vaccine group (of 112 participants; 1.8%). Eighty-eight patients with COVID-19 disease were included in the analysis. The average age as of the study enrollment was 66 (range 39-81) and the majority of patients were male with renal cell carcinoma (RCC). Thirty-six patients (41%) had evidence of metastatic disease, of these 22 patients were receiving systemic therapy. More than half of patients required hospitalization. Fifty-four patients (61%) experienced complications. Sixteen patients who developed COVID-19 pneumonia required mechanical ventilator support. Sixteen patients (18%) died in a median of 23.5 days after the date of COVID-19 diagnosis was established. The 3-month survival rate was 82%. Clinical and/or radiographic progression of cancer during COVID-19 infection or the subsequent 3 months was observed in 10 patients (11.4%). CONCLUSION: Patients with GU malignancies are at increased risk of mortality from COVID-19 infection when compared to the general population. Vaccination could be safe in GU cancer patients. TRIAL REGISTRATION: retrospectively registered.