An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19)

Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/ progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity;and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Disruption to care of patients with thoracic malignancies: A COVID-19 and cancer outcomes study

Introduction: Patients with thoracic malignancies are susceptible to severe outcomes from coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the disruption to care of patients with thoracic malignancies during the COVID-19 pandemic. Methods: The COVID-19 and Cancer Outcomes Study (CCOS) is a multicenter prospective cohort study comprised of adult patients with a current or past history of hematological malignancy or invasive solid tumor who had an outpatient medical oncology visit on the index week between March 2 and March 6, 2020 at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York, NY (MSSM) or the Dana-Farber Cancer Institute in Boston, MA (DFCI). An electronic data capture platform was used to collect patient-, cancer-, and treatment-related variables during the three months prior to the index week (the baseline period) and the following three months (the pandemic period). Two-by-three contingency tables with Fisher's exact tests were computed. All tests were two-tailed and considered statistically significant for p<0.05. All analyses were done in the R statistical environment (v3.6.1). Results: The overall cohort included 2365 patients, of which 313 had thoracic malignancies, 1578 had other solid tumors, and 474 had hematological malignancies. At a median follow-up of 84 days (95% confidence interval, 82-84), 13 patients with thoracic malignancies (4.1%) had developed COVID-19 (vs. other solid: 63 [4.0%] and hematological: 52 [11.0%];p<0.001). When comparing data from the pandemic period to the baseline period, patients with thoracic malignancies had a decrease in the number of in-person outpatient visits (thoracic: 209 [66.8%] vs. other solid: 749 [47.5%] vs. hematological: 260 [54.9%];p<0.001) and an increase in the number of telehealth visits (thoracic: 126 [40.3%] vs. other solid: 465 [29.5%] vs. hematological: 168 [35.4%];p<0.001). During the pandemic period, 33 (10.5%) patients with thoracic malignancies experienced treatment delays due to the pandemic (vs. other solid: 127 [8.0%] and hematological: 79 [16.7%];p<0.001), and 26 (8.3%) patients with thoracic malignancies experienced delays in cancer imaging or diagnostic procedures (vs. other solid: 63 [4.0%] and hematological: 26 [5.5%];p=0.003). Discussion: In this prospective cohort study, patients with thoracic malignancies were not at increased risk of developing COVID-19 compared to patients with other cancers, but experienced significant cancer care disruption during the COVID-19 pandemic with a higher likelihood of decreased in-person visits and increased telehealth visits compared to patients with other malignancies. Focused efforts to ensure continuity of care for this vulnerable patient population are warranted.

Temporal changes in the screening, diagnosis and surgical treatment of genitourinary (GU) malignancies during the COVID-19 pandemic

Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COVID-19 pandemic. Methods: We evaluated screening, novel diagnoses, and surgical management modalities of prostate cancer (PCa), urothelial carcinoma (UC) and renal cell carcinoma (RCC) within Massachusetts General Brigham, the largest healthcare system in the Northeastern United States, over four 3-month time periods during the pandemic (March 2020- March 2021). The percentage change in screening, diagnoses and management modalities during pandemic periods as compared to the immediate pre-pandemic period (December 2019-March 2020) was calculated as (Nperiod - Ncontrol)/Ncontrol. The difference in "predicted" versus "observed" diagnoses in each pandemic period was compared to the average of the four preceding 3-month periods (March 2019-March 2020) to account for seasonal variation. Results: The first pandemic peak (March-June 2020) was associated with a significant decline across screening, diagnosis and treatment, ranging from -15.7 to -64.8%, followed by a progressive recovery, ranging from -5.9 to +25.1% in the latest period (December 2020-March 2021) (Table). Although 725 diagnoses were "missed" between March and June 2020 as compared to the previous 12 months, 971 diagnoses were "recovered" between June 2020 and March 2021. Conclusions: A substantial disruption in the screening, diagnosis and treatment of GU malignancies was observed early in the pandemic, followed by a progressive rebound and recovery. The highest declines were observed for PSA screening, and the lowest for cystectomy procedures, reflecting triaging of care based on severity during the pandemic.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Lower respiratory tract disease (LRTD) in patients with cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) study

Background: Immunodeficiency in patients (pts) with cancer can lead to the progression of common respiratory viral infections to lower respiratory tract disease (LRTD) with potentially high mortality. Understanding risk factors of SARS-CoV-2 related LRTD in pts with cancer is imperative for the development of preventive measures. Methods: We examined all patients aged 18 years or older with cancer and laboratory-confirmed SARS-CoV-2 infection reported between March 16, 2020 and February 6, 2021 in the international CCC19 registry. We examined frequency of LRTD (pneumonia, pneumonitis, acute respiratory distress syndrome, or respiratory failure), demographic and clinicopathologic factors associated with LRTD, and 30-day and overall mortality in pts with and without LRTD. Results: Of 7,289 pts with a median follow-up time of 42 (21-90) days, 2187 (30%) developed LRTD. Pts of older age (65 yrs or older), male sex, pre-existing comorbidities, baseline immunosuppressants, baseline corticosteroids, and ECOG performance status of 2 or more had substantially higher rates of LRTD compared to those without these risk factors (Table). We did not observe differences in LRTD rates between pts of different racial/ethnic groups, smoking history, hypertension, obesity, cancer status, timing or type of anti-cancer therapy. LRTD was more likely in pts with thoracic malignancy (39%), hematological malignancy (39%) compared to those with other solid tumors (27%). The majority of pts (86%) had symptomatic presentation;however, 8% of pts with asymptomatic presentation developed LRTD. 30-day and overall mortality rates were significantly higher in pts with LRTD than those without LRTD (31% vs. 4% and 38% vs. 6%, P < 0.05). Conclusions: COVID-19 related LRTD rate is high and associated with worse mortality rates in pts with cancer. The majority of risk factors associated with LRTD demonstrate underlying immunodeficiency or lung structural damage as a driving force in this population. Identifying pts at high-risk for developing LRTD can help guide clinical management, improve pt outcomes, increase the cost-effectiveness of antiviral therapy, and direct future clinical trial designs for vaccine or antiviral agents. (Table Presented).

Racial and ethnic disparities among patients with breast cancer and COVID-19

Background: Racial/ethnic minorities have disproportionately increased risk of contracting COVID-19 and experiencing severe illness;they also have worse breast cancer (BC) outcomes. COVID-19 outcomes among racial/ethnic minorities with BC are currently unknown. We sought to compare clinicopathologic characteristics and COVID-19 outcomes stratified by race/ethnicity. Methods: The COVID-19 and Cancer Consortium registry (NCT04354701) was used to identify patients with invasive BC and laboratory-confirmed SARS-CoV-2 diagnosed in the U.S. between 2020-03-06 and 2021-02-04. The primary analysis was restricted to women who selfidentified as non-Hispanic White (NHW), nonHispanic Black (NHB), or Hispanic (H). Demographic, cancer characteristics, and COVID-19 outcomes were evaluated. COVID-19 outcomes included: hospital admission, intensive care unit (ICU) admission, mechanical ventilation, death within 30 days of COVID-19 diagnosis and death from any cause during follow-up. Descriptive statistics were used to compare clinicopathologic characteristics and Fisher exact tests were used to compare COVID19 outcomes across the 3 racial/ethnic groups. Results: A total of 1133 patients were identified of which 1111 (98%) were women;of which 575 (52%) NHW, 243 (22%) NHB, 183 (16%) H, and 110 (10%) other/unknown. Baseline characteristics differed among racial/ethnic groups. H were younger (median age: NHW 63y;NHB 62y;H 54y) and more likely to be never smokers (NHW 62%;NHB 62%;H 78%). NHB had higher rates of obesity (NHW 40%;NHB 54%;H 46%), diabetes (NHW 16 %;NHB 32%;H 20%) and combined moderate and severe baseline COVID-19 at presentation (NHW 28%;NHB 42%;H 28%). Cancer characteristics are as shown (Table). Significant differences were observed in outcomes across racial/ethnic groups including higher rates of hospital admission (NHW 34%;NHB 49%;H 34%;P <0.001), mechanical ventilation (NHW 3%;NHB 9%;H 5%;P=0.002), 30-day mortality (NHW 6%;NHB 9%;H 4%;P=0.043) and total mortality (NHW 8%;NHB 12%;H 5%;P=0.05) among NHB compared to NHW and H. Conclusions: This is the largest study to show significant differences in COVID-19 outcomes by racial/ethnic groups of women with BC. The adverse outcomes in NHB could be due to higher moderate to severe COVID-19 at presentation and preexisting comorbidities. H did not have worse outcomes despite having more active disease and recent anti-cancer therapy, including with cytotoxic chemotherapy - potentially due to younger age and nonsmoking status. (Table Presented).

Effect of bacillus calmette-guerin (BCG) exposure on severity of COVID-19 infection: A COVID-19 and cancer consortium (CCC19) study

Background: Oncology patients experience more severe disease outcomes from COVID-19 infection than the general population. BCG is a live bovine tuberculosis bacillus with immunotherapeutic effects in urothelial cancers;it is also used as vaccination against Mycobacterium tuberculosis in parts of the world. As BCG vaccination has been associated with broad protection against viral pathogens, BCG exposure through vaccination or intravesical therapy may modulate host immunity and reduce the severity of COVID-19 infection. We report the effect of BCG exposure on COVID-19 severity in oncology patients from the CCC19 registry. Methods: The CCC19 registry (NCT04354701) was used to identify patients with prior BCG exposure. Cohort A received intravesical treatment for bladder carcinoma, and cohort B received prior BCG vaccination. Each cohort was matched 3:1 to non-BCG-exposed controls by age, sex, race, primary cancer type, cancer status, ECOG performance status (PS) and calendar time of COVID-19 infection. The primary endpoint was COVID-19 severity reported on an ordinal scale (uncomplicated, hospitalized, admitted to ICU +/- ventilated, died within 30 days) of patients exposed to prior BCG compared to matched non-exposed controls. 2-sided Wilcoxon ranksum tests were used. Results: As of 6-Feb-2021 we included 124 patients with BCG exposure, 68 patients with bladder carcinoma who had received intravesical BCG (Cohort A), and 64 cancer patients with prior BCG vaccination (Cohort B). Median age was 76 years, IQR 69-83 (Cohort A) and 67 years, IQR 62-74 (Cohort B). Bladder cancer pts were predominately male (78%) vs 55% for Cohort B. Patients with PS 2+ were uncommon, 18% in Cohort A and 16% in Cohort B. COVID-19 illness severity was no different in patients exposed to prior intravesicular BCG (p=0.87). COVID-19 illness severity was no different in patients exposed to prior intradermal BCG vaccination (p=0.60). Conclusions: Despite this being the largest such cohort reported to date, we failed to demonstrate an association of prior BCG exposure with modulation of severity of COVID19 illness. Prospective trials evaluating the protective effect of BCG vaccination are ongoing and will add further insight into the effect of BCG on COVID-19 illness.

Disparities in cancer during the COVID-19 pandemic: COVID-19 and cancer outcomes study (CCOS)

Background: The COVID-19 pandemic has rapidly altered cancer care. However, the ways in which it has done so and the associated impact at the individual and societal levels remains poorly defined. Methods: CCOS is a multicenter prospective cohort study designed to define the impact of the pandemic on cancer care delivery and outcomes. The CCOS cohort comprised consecutive outpatients with cancer seen at two US cancer centers from March 2 to March 6, 2020 (index visit). Data was collected at baseline, retrospectively from the preceding 3 months, and prospectively at 3-month follow up. Per patient changes in numbers of visits were compared using Wilcoxon signed rank tests. Correlates of increases in telehealth visits and decreases in in-person visits were evaluated using multivariable logistic regression models. Adjusted Odds ratios [aOR] and 95% confidence intervals (CI) were reported. Results: Of 2365 included patients, 1219 (51.6%) had a decrease in in-person visit frequency during the pandemic period relative to the preceding 3 months. Conversely, 760 (32.2%) had an increased frequency of telehealth visits (decrease in in-person and increase in telehealth visits;both p<0.01). 128 (5.4%) patients developed COVID-19. Compared to White patients, Black and Hispanic patients were less likely to have telehealth visits, had no significant change in frequency of in-person visits, and were more likely to develop COVID-19 (Table). [Formula presented] Conclusions: Significant disruptions to routine cancer care were observed during the pandemic period relative to the prior 3 months. Racial and ethnic barriers to the adoption of telehealth, and related socioeconomic factors, place these vulnerable populations simultaneously at disproportionate risk for decreased cancer-related visits and COVID infection, thereby exacerbating existing racial and ethnic health disparities. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: D. Doroshow: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen;Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy: Athenaeum Partners;Honoraria (self), Advisory/Consultancy: Boston Healthcare Associates. A.L. Schmidt: Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: Astellas. Z. Bakouny: Non-remunerated activity/ies: Bristol Myers Squibb;Research grant/Funding (self): Genentech/ImCore. M.M. Awad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Lilly;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy: Merck;Advisory/Consultancy: Achilles;Advisory/Consultancy: AbbVie. R. Haddad: Advisory/Consultancy, Research grant/Funding (self): Bristol Myers Squibb;Advisory/Consultancy, Research grant/Funding (self): Merck;Advisory/Consultancy, Research grant/Funding (self): Pfizer;Advisory/Consultancy, Research grant/Funding (self): Genentech;Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline. M.D. Galsky: Shareholder/Stockholder/Stock options: Rappta Therapeutics;Honoraria (self): BioMotiv;Honoraria (self): Janssen;Honoraria (self): Dendreon;Honoraria (self): Merck;Honoraria (self): GlaxoSmithKline;Honoraria (self): Lilly;Honoraria (self): Astellas Pharma;Honoraria (self): Genentech;Honoraria (self): Bristol-Myers Squibb;Honoraria (self): Novartis;Honoraria (self): Pfizer;Honoraria (self): EMD Serono;Honoraria (self): AstraZeneca;Honoraria (self): Seattle Genetics;Honoraria (self): Incyte;Honoraria (self): Alleron Therapeutics;Honoraria (self): Dracen;Honoraria (self): Inovio Pharmaceuticals;Honoraria (self): NuMab;Honoraria (self): Dragonfly Therapeutics;Honoraria (institution): Janssen Oncology;Honoraria (institution): Dendreon;Honoraria (institution): Novartis;Honoraria (institu ion): Bristol-Myers Squibb;Honoraria (institution): Merck;Honoraria (institution): AstraZeneca;Honoraria (institution): Genentech/Roche. T.K. Choueiri: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Alexion;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): BristolMyersSquibb;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Cerulean;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Eisai;Honoraria (self), Research grant/Funding (self): Foundation Medicine;Honoraria (self), Research grant/Funding (self): Exelixis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Ipsen;Research grant/Funding (self): 16 Tracon;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Genentech;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche;Honoraria (self), Research grant/Funding (self): Roche Products Limited;Honoraria (self), Research grant/Funding (self): Hoffman-LaRoche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): GlaxoSmithKline;Advisory/Consultancy, Research grant/Funding (self): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Merck;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Peloton;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Prometheus labs;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Corvus;Research grant/Funding (self): Calithera;Research grant/Funding (self): Analysis Group;Honoraria (self), Research grant/Funding (self): Sanofi/Aventis;Research grant/Funding (self): Takeda;Honoraria (self), Advisory/Consultancy: EMD Serono;Honoraria (self), Advisory/Consultancy: UpToDate;Honoraria (self): NCCN;Honoraria (self), Advisory/Consultancy, Dr. Choueiri reports research support from AstraZeneca, Alexion, Bayer, Bristol Myers Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Ipsen, 16 Tracon, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Lilly, Merck, Novartis, Peloton, Pfizer, Prometheus Labs, Corvus, Calithera, Analysis Group, Sanofi/Aventis, Takeda;Honoraria: AstraZeneca, Alexion, Sanofi/Aventis, Bayer, Bristol Myers-Squibb/ER Squibb and sons LLC, Cerulean, Eisai, Foundation Medicine Inc., Exelixis, Genentech, Roche, Roche Products Limited, F. Hoffmann-La Roche, GlaxoSmithKline, Merck, Novartis, Peloton, Pfizer, EMD Serono, Prometheus Labs, Corvus, Ipsen, Up-to-Date, NCCN, Analysis Group, NCCN, Michael J. Hennessy (MJH) Associates, Inc (Healthcare Communications Company with several brands such as OnClive, PeerView and PER), Research to Practice, L-path, Kidney Cancer Journal, Clinical Care Options, Platform Q, Navinata Healthcare, Harborside Press, American Society of Me: Analysis Group. All other authors have declared no conflicts of interest.