key: cord-0959715-kb9m508x
authors: Smeltzer, M.; Bunn, P. A.; Clark, R.; Arndt, R.; Pruett, C.; Roy, U.; Hirsch, F.; Mitsudomi, T.; Wakelee, H.; Scagliotti, G.
title: PL02.09 International Association for the Study of Lung Cancer (IASLC) Study of the Impacts of COVID-19 on International Lung Cancer Clinical Trials
date: 2021-10-31
journal: Journal of Thoracic Oncology
DOI: 10.1016/j.jtho.2021.08.033
sha: 31ac46489703bd086b1edc93fefcaae7d483307c
doc_id: 959715
cord_uid: kb9m508x

nan

Introduction: In 2020, the global COVID-19 pandemic created major barriers to enrollment and completion of clinical trials. We surveyed investigators and collected aggregate enrollment data for lung cancer trials across the world before (2019) and during (2020-2021) the COVID-19 pandemic. Methods: This study consisted of two components. The 64-question Action Survey, distributed by email to select international clinical trial sites, assessed the impact of COVID-19 on the conduct of clinical trials at 173 sites in 2019-2021 and identified mitigation strategies used to combat these impacts. The Data Collection Survey collected aggregate enrollment numbers monthly from 171 lung cancer trials for 2019-2020. Data sources included government or regulatory agencies, industry sponsors, and Principal Investigators from 45 countries. We evaluated enrollment monthly and estimated Incidence Rate Ratios (IRR) with 95% confidence intervals (CI) by Generalized Estimating Equations. Types of Analysis and Data Reporting: Aims of the study include: a) results from the Action Survey will be summarized to help understand the details of the impact COVID-19 had on clinical trials for lung cancer. We will report and evaluate mitigation strategies by region, economic status, trial type and COVID-19 burden; b) we will evaluate trial enrollment data from the Data Collection Survey over time by global region, trial type, and regional COVID-19 burden in simple analysis and with longitudinal statistical models; c) we will combine information from the Action Survey and Data Collection Survey to quantitatively evaluate the impact of mitigation strategies on clinical trial enrollment for trials open at the respective institutions. These results will be stratified by region, economic status, trial type, and regional COVID-19 burden. Additional analysis on how these strategies may impact patients will be included. Results: Clinical trial enrollment declined by 43% from 2019 to 2020 (IRR: 0.57 [CI: 0.37, 0.88]) p¼0.0115), with the most dramatic decrease April-August ( Figure 1 ). Although monthly COVID-19 cases increased consistently for all of 2020, the impact on trial enrollment was significantly less in October-December compared to April-June of 2020 (p¼0.0160, Figure 1 ). The most frequent challenges identified by the Action Survey (N¼173) were fewer eligible patients (67%), suspension of trials (60%), institutional closures (39%), research staff availability (48%), and protocol compliance (61%). Overall 26% of sites reported disruptions from trial participants COVID-19 infection and 40% from exposurerelated quarantine. Patient-specific challenges included access to trial site (52%), ability to travel (60%), and willingness to visit site (63%). Patient concerns included fear of COVID-19 infection (83%), securing transportation (38%), travel restrictions (47%), and lab/ radiology access (14%). The Action Survey identified the most frequent mitigation strategies sites employed, which included modified monitoring requirements (44%), telehealth visits (43%), modified required visits (25%), mail-order medications (24%), and altered trial schedules (19%). Some sites allowed labs (27%) and radiology (20%) at non-study facilities and a few implemented altered (7%) or electronic (10%) consent processes. Sites felt the most effective mitigation strategies were delayed visits (65%), remote monitoring (64%), delayed assessment (62%), IRB changes (62%), remote symptom monitoring (59%) or diagnostics (59%), and telehealth visits (59%).

The COVID-19 pandemic created many challenges causing reductions in lung cancer clinical trial enrollment. Mitigation strategies were employed and, even though the pandemic worsened, trial enrollment began to improve. A more flexible approach -removing unnecessary barriers-may improve enrollment and access to clinical trials, even beyond the pandemic. Introduction: Patients with lung cancer (LC) were reported to have a high case fatality rate (30-40%) from SARS-CoV-2 infection, raising the question of whether LC patients mount a weaker antibody response to natural infection and/or vaccination, compared to healthy controls (HCs). We previously analyzed antibody responses to SARS-CoV-2 mRNA vaccination in several hundred healthy individuals, stratified by previous SARS-CoV-2 infection status. Using a validated enzyme-linked immunosorbent assay (ELISA) to the full-length spike protein (PMC8183627, PMC7235504), we found strong responses to infection and a robust neutralizing antibody response to vaccination. We compare these results to data from individuals diagnosed with LC undergoing different types of cancer treatment. Methods: This is an ongoing, prospective, control-matched longitudinal cohort study of 750 LC patients in all stages with or without previous SARS-CoV-2 infection and/or vaccination, comparing SARS-CoV-2 antibody titers at baseline (time of enrollment) and at 3-, 6-, 12-and 24-month intervals. We examine the quality, magnitude, and duration of the SARS-CoV-2 antibody titers against the full-length spike protein compared to the matched (age, tobacco history, sex and ethnicity) HC cohort. Types of Analysis and Data Reporting: ELISAs are performed in a CLIAcertified laboratory using an FDA-approved antibody assay along with other well-established, research-grade assays. We hypothesized that LC patients have a weaker antibody response to SARS-Cov-2 infection and/or vaccination due to cancer or its treatment compared to matched HCs. The non-parametric KruskaleWallis test was used to test this hypothesis. If confirmed, a tailored vaccination program would be necessary to ensure immune protection in patient with LC. Results: 111 LC patients have been enrolled to date; with 78 receiving at least one vaccination and 33 unvaccinated. Median age is 69, with 58% female. 39 patients were fully vaccinated (defined as 14+ days after second vaccination). Partially vaccinated (after 1 st vaccine dose) LC patients had a lower median antibody level than partially vaccinated HCs (p¼0.01). Fully vaccinated LC patients had substantial antibody titers but a lower median antibody level than fully vaccinated HCs (p¼0.01) with a subset not raising large antibody titers. Especially important were the 30% of partially vaccinated LC patients who did not develop neutralizing antibodies. To date, there were no significant differences in median antibody levels in LC patients by gender, smoking status, age (< or > 65 years old), or treatment (with or without chemotherapy, immune checkpoint inhibitors, or targeted therapy). Conclusion: While most (w70%+) of LC patients mounted a good antibody response to vaccination, a subgroup had significantly lower anti-spike antibody/neutralizing levels compared to controls. Further studies are required to evaluate the role of further boost vaccinations in this patient population with a particular focus on patients not producing neutralizing antibodies to further understand the lack of response. We will continue to analyze the effect of systemic anti-cancer therapies as more data becomes available. Keywords: SARS-CoV-2, lung cancer, covid-19 OA01.02 Impact of COVID-19 Outbreak on Lung Cancer Diagnosis and Continuum of Care: Data From an Italian Multicenter Study

10 E. Rijavec, 11 R. Chiari, 12 S. Oldani, 13 A. Caglio

Rome/IT, 5 Medical Oncology Unit, Careggi University Hospital, Firenze/IT, 6 Pneumo-Oncology Unit, Monaldi Hospital, Napoli/ IT, 7 Medical Oncology, A.O. Papardo & Department of Human Pathology, University of Messina, Messina/IT, 8 Medical Oncology, Irccs Ospedale Policlinico San Martino, Genova/IT, 9 Thoracic Medical Oncology, Istituto Nazionale Tumori -Irccs -Fondazione G. Pascale, Naples/IT, 10 Oncology Unit, Irccs Ospedale Sacro Cuore Don Calabria Negrar, Verona/IT, 11 Medical Oncology, Fondazione Irccs Ca' Granda Ospedale Maggiore Policlinico, Milano/IT, 12 Medical Oncology, Ospedali Riuniti Padova Sud "madre Teresa Di Calcutta