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Background: As management and prevention strategies against Coronavirus Disease-19 (COVID-19) evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients (pts) with cancer. Method(s): In a joint analysis of ICI recipients from OnCovid (NCT04393974) and ESMO CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated pts with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19. Result(s): The study population consisted of 240 pts diagnosed with COVID-19 between Jan 2020 and Feb 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95%CI: 17.8-30.7%). 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30 (4.8% vs 28.1%, p=0.001), hospitalization rate (27.5% vs 63.2%, p<0.001), requirement of oxygen therapy (15.8% vs 41.5%, p=0.003), COVID-19 complication rate (11.9% vs 34.6%, p=0.004), and COVID-19-specific therapy (26.3% vs 57.9%, p=0.001) compared with unvaccinated pts. IPTW-fitted multivariable analysis, following a clustered-robust correction for the data source (OnCovid vs ESMO CoCARE), confirmed that vaccinated pts experienced a decreased risk of death at 30 days (aOR 0.08, 95%CI: 0.01-0.69). 38 pts (15.8%) experienced at least 1 irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (0.13-48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumour (p=0.037) and were associated with a significantly decreased CFR30 (10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR: 0.47, 95%CI: 0.33-0.67). Pts who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.009). Conclusion(s): Anti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify pts with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2. Clinical trial identification: NCT04393974 OnCovid. Legal entity responsible for the study: Imperial College London & ESMO. Funding(s): Imperial Biomedical Research Centre ESMO. Disclosure: A. Cortellini: Financial Interests, Personal, Advisory Board: MSD, OncoC4;Financial Interests, Personal, Invited Speaker: Eisai, AstraZeneca;Financial Interests, Personal, Expert Testimony: Iqvia. D.J. Pinato: Financial Interests, Personal, Invited Speaker: ViiV Healthcare, Bayer, BMS, Roche, Eisai, Falk Foundation;Financial Interests, Personal, Advisory Board: Mina Therapuetics, Eisai, Roche, DaVolterra, AstraZeneca. All other authors have declared no conflicts of interest. Copyright © 2022 European Society for Medical Oncology
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Background: The Omicron (B.1.1.529) SARS-CoV-2 variant is highly transmissible and escapes vaccinal immunity. Evidence is lacking as to the impact of Omicron in oncological patients. Method(s): Capitalizing on OnCovid study data (NCT04393974), we analysed COVID-19 morbidity and case fatality rate at 28 days (CFR28) of unvaccinated patients across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: "Pre-vaccination" phase (27/02/2020-30/11/2020), "Alpha- Delta variant" phase (01/12/2020-14/12/2021), "Omicron variant" phase (15/12/2021-31/01/2022). Finding(s): By the data lock of 04/02/2022, 3820 patients from 37 institutions across 6 countries were entered. Out of 3473 eligible patients, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. In total 659 (61.3%) and 42 (11.5%) were unvaccinated in the Alpha-Delta and Omicron. Unvaccinated patients across the Omicron, Alpha-Delta and Pre-vaccination phases experienced similar CFR28 (27.5%, 28%, 29%, respectively). Following propensity score matching, 42 unvaccinated Omicron patients were matched with 122 and 121 patients from the Pre-vaccination and Alpha-Delta phases respectively, based on country of origin, sex, age, comorbidity burden, primary tumour, cancer stage and status, and the receipt of systemic anticancer therapy at COVID-19. Unvaccinated Omicron patients experienced improved COVID-19 outcomes in comparison to patients diagnosed during the Prevaccination phase. Morbidity and mortality were comparable to those of unvaccinated patients diagnosed during the Alpha-Delta phase. Interpretation(s): Despite time-dependent improvements in outcomes reported in the Omicron phase, patients with cancer remain highly vulnerable to SARS-CoV-2 in absence of vaccinal protection. This study provides unequivocal evidence in support of universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.
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Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR14) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts' characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.
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Background: Whilst patients (pts) with cancer are at increased risk of adverse outcome from Coronavirus disease 2019 (COVID-19), no evidence exists as to the natural history of the SARS-CoV-2 B.1.1.529 (Omicron) variant in this population. Methods: Capitalizing on OnCovid study data (NCT04393974), a European registry that collects data on consecutive patients with cancer and COVID-19, we analysed COVID-19 morbidity and case fatality rates at 14 days (CFR14) across 3 phases defined following the evolution of the pandemic in Europe, according to date of COVID-19 diagnosis: “Pre-vaccination” phase (27/02/2020-30/ 11/2020), “Alpha-Delta variant” phase (01/12/2020-14/12/2021), “Omicron variant” phase (15/12/2020-31/01/2022). Results: By the data lock of 04/02/2022, 3820 consecutive pts were enrolled, 3473 of whom were eligible for this analysis. Among them, 2033 (58.6%), 1075 (30.9%) and 365 (10.5%) were diagnosed during the Pre-vaccination, Alpha-Delta and Omicron phases. Pts diagnosed in the Omicron phase were more likely aged < 65 years (48.6% vs 42.5%, 39.4% p = 0.01), had < 2 comorbidities (61.9% vs 55.6%, 52.1% p = 0.01). They had more advanced-stage tumours (62.1% vs 53.3%, 49.0%, p < 0.01) and were more likely receiving systemic anticancer therapy (SACT) at COVID-19 diagnosis (54.9% vs 43.9%, 39.6%, p < 0.01). Proportions of fully vaccinated/boosted pts were higher in the Omicron phase (33.9%-48.1%) compared to the Alpha-Delta phase (16.6%-2.3%, p < 0.01). Pts diagnosed in the Omicron phase had improved CFR14 (9.0% vs 13.9%, 23.1%, p < 0.01) lower hospitalization rates due to COVID-19 (24.4% vs 41.4%, 56.6%, p < 0.01), lower complications rates (15.3% vs 33.6%, 39.4%, p < 0.01) and reduced need for COVID-19 specific therapy (22.4% vs 43.0%, 65.7% p < 0.01) compared to the Alpha-Delta and pre-vaccinal phase. After adjusting for country of origin, sex, age, comorbidities, tumour stage, status and receipt of SACT at COVID-19, patients diagnosed in the Omicron phase displayed the lowest risk of death at 14 days compared to earlier phases. Similarly, rates of hospitalization and complicated COVID-19 were lowest for Omicron phase. Conclusions: This is the first study to portray the evolution of the SARS-CoV-2 Omicron outbreak in Europe, documenting an improvement in all COVID-19 outcomes compared to earlier phases of the pandemic. Enhanced healthcare capacity, improved disease management, immunization campaigns alongside differential virulence of viral strains are likely contributing to improved outcomes across phases.
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Background: Trans-arterial chemoembolization (TACE) is the gold-standard for intermediate stage HCC. We hypothesised the ischemic and cytotoxic effect of TACE to boost anti-cancer immunity and to synergise with the anti PD-1 pembrolizumab (pembro). We designed a phase Ib study to test the safety and preliminary efficacy of pembro after TACE in intermediate HCC. Methods: PETAL study will enroll up to 32 patients with intermediate HCC to receive pembro 200 mg every 3 weeks for up to 1 year or until disease progression or unacceptable toxicity. The first safety-run-in phase includes 6 patients: if no dose limiting toxicities (DLTs) emerge over a 21-day window after first pembro, the others are enrolled in the expansion phase. Pembro is given within 30 days after 1 or 2 TACEs. The first phase includes 1 patient scoring Child-Pugh (CP)-B7 and the remaining have to be CP-A. Safety is the primary endpoint and is measured as the incidence of treatment-related adverse events (TRAEs), graded according to NCI CTCAEv4. Efficacy is the secondary endpoint and is evaluated as progression free survival (PFS) from first TACE, according to mRECIST criteria. Survival is estimated using Kaplan-Meier method. All the patients who have received at least one dose of pembro are evaluable for safety. Results: At the time of data cut-off, on the 14th of January 2022, 14 patients had received at least one dose of pembro. The median age was 72 (IQR: 63.3-74.6), 79% were male, 71% were cirrhotic, 29% had viral hepatis and 43% ECOG PS 1. One patient had Child-Pugh (CP) class B7 and 13 had A. The median number of nodules was 1.5 (IQR:1-2.8), and 4.1 cm (IQR: 3.7-4.5) the median diameter. Overall, 5 patients received 2 TACEs and 9 had 1. Patients received a median of 4.5 cycles (IQR: 2.3-6.5) of pembro. No DLTs emerged in the first phase. Treatment-related adverse events (TRAE) of any grade (G) were reported in 86% of participants, 21% of participants experienced G3 TRAEs, and there were no G4 or G5 TRAEs. Specific skin-related toxicity was the most frequently reported (35%) TRAE. No patients had treatment-related liver toxicity. Causes of treatment discontinuation were PD (n=7), TRAEs (n=1), clinical deterioration in the CP B patient (n=1), COVID pandemic (n=2) and withdrawal of consent (n=1);at the time of data cut-off, mPFS from first TACE was 10.8 months (95%CI: 6.63-14.97). Conclusions: Adjuvant pembro following TACE is manageable and tolerable with signs of activity. These results prompt the investigation in larger trials.
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INTRODUCTION: COVID-19 has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak had an impact on access to cancer diagnosis and treatment of LC pts compared with pre-pandemic time. METHODS: Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared with the same period in 2019. Differences between the 2 years were analyzed using the chi-square test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 versus 1637, P = 0.09). Newly diagnosed LC pts in 2020 were more likely to be diagnosed with stage IV disease (P < 0.01) and to be current smokers (someone who has smoked more than 100 cigarettes, including hand-rolled cigarettes, cigars, cigarillos, in their lifetime and has smoked in the last 28 days) (P < 0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% versus -3.2%) compared with the other months included. More LC pts were referred to a low/medium volume hospital in 2020 compared with 2019 (P = 0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (P = 0.94), symptoms onset and cytohistological diagnosis (P = 0.92), symptoms onset and treatment start (P = 0.40), and treatment start and first radiological revaluation (P = 0.36). CONCLUSIONS: Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
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COVID-19 , Lung Neoplasms , Communicable Disease Control , Humans , Italy/epidemiology , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Lung Neoplasms/therapy , PandemicsABSTRACT
Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment.
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Background: Little is known about natural anti-SARS-CoV-2 antibody seroprevalence post COVID-19 and safety of vaccines in COVID-19 survivors with cancer. Methods: Among 2795 consecutive patients (pts) with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined natural seroprevalence of anti-SARS-CoV-2 Antibodies (SC2Ab, IgM or IgG) in pts tested post-infection. We analysed prevalence and safety of SARS-Cov-2 vaccine administration in pts who underwent clinical re-assessment at participating institutions. Results: Out of 350 pts tested for SC2Ab, 318 (90.9%) had a positive SC2Ab titre post-convalescence. Neither baseline features (sex, age, comorbidities, smoking history, tumour stage/status, anticancer-therapy and primary tumour) nor COVID-19-specific features (complications, hospitalization, sequelae) were significantly associated SC2Ab status. Receipt of COVID-19 specific therapy was higher among SC2Ab+ pts (62.6% vs 40.6%, p=0.0156). Out of 593 pts with known vaccination status, 178 (30%) had received 1 dose, whilst 38 pts (6.4%) received 2 doses of mRNA based (70.2%) or viral vector vaccine (17.4%). Vaccinated pts were more likely aged ≥65 years (59% vs 48.3%, p=0.0172), with loco-regional tumour stage (56% vs 40.8%, p=0.0014), on anti-cancer therapy at COVID-19 (49.1% vs 38.2%, p=0.0168) and history of prior hospitalisation due to COVID-19 (61.8% vs 48.3%, p=0.0029). Vaccine-related adverse events were reported for 18/56 evaluable pts (32.1%) and included injection site reactions (50%), fever (44.4%), arthralgias (33.3%), fatigue (33.3%) and allergy (5.5%). No long-term vaccine-related morbidity was reported. Conclusions: We report high seroprevalence (>90%) of SC2Ab in convalescent cancer pts who survived COVID-19 irrespective of baseline demographics, oncological characteristics and COVID-19 severity. COVID-19 vaccines appear to be safe in cancer pts with history of prior infection. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Invited Speaker: ViiV Healthcare;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Eisai;Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Nanostring tech. A. Cortellini: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Advisory Board: SunPharma;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Astellas. All other authors have declared no conflicts of interest.
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Background: Early reports from registry studies demonstrated high vulnerability of cancer patients from COVID-19, with case-fatality rates (CFR) >30% at the onset of the pandemic. With advances in disease management and increased testing capacity, the lethality of COVID-19 in cancer patients may have improved over time. Methods: The OnCovid registry lists European cancer patients consecutively diagnosed with COVID-19 in 35 centres from Jan 2020 to Feb 2021. We analysed clinical characteristics and outcomes stratified in 5 trimesters (Jan-Mar, Apr-Jun, Jul-Sep, Oct-Dec 2020 and Jan-Feb 2021) and studied predictors of mortality across 2 semesters (Jan-Jun 2020 and Jul 2020-Feb 2021). Results: At data cut-off, the 2634 eligible patients demonstrated significant time-dependant improvement in 14-days CFR with trimestral estimates of 29.8%, 20.3%, 12.5%, 17.2% and 14.5% (p<0.0001). Compared to the 2nd semester, patients diagnosed in the Jan-Jun 2020 time period were ≥65 (60.3% vs 56.1%, p=0.031) had ≥2 comorbidities (48.8% vs 42.4%, p=0.001) and non-advanced tumours (46.4% vs 56.1%, p<0.001). COVID-19 was more likely to be complicated in Jan-Jun 2020 (45.4% vs 33.9%, p<0.001), requiring hospitalization (59.8% vs 42.1%, p<0.001) and anti-COVID-19 therapy (61.7% vs 49.7%, p<0.001). The 14-days CFR for the 1st and 2nd semester was 25.6% vs 16.2% (p<0.0001), respectively. After adjusting for gender, age, comorbidities, tumour features, COVID-19 and anti-cancer therapy and COVID-19 complications, patients diagnosed in the 1st semester had an increased risk of death at 14 days (HR 1.68 [95%CI: 1.35-2.09]), but not at 3 months (HR 1.10 [95%CI: 0.94-1.29]) compared to those from the 2nd semester. Conclusions: We report a time-dependent improvement in the mortality from COVID-19 in European cancer patients. This may be explained by expanding testing capacity, improved healthcare resources and dynamic changes in community transmission over time. These findings are informative for clinical practice and policy making in the context of an unresolved pandemic. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Financial Interests, Personal, Speaker’s Bureau: ViiV Healthcare;Financial Interests, Personal, Speaker’s Bureau: Bayer;Financial Interests, Personal, Advisory Board: EISAI;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: AstraZeneca. All other authors have declared no conflicts of interest.
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Background: The long-term impact of COVID-19 in cancer patients (pts) is undefined. Methods: Among 2795 consecutive pts with COVID-19 and cancer registered to OnCovid between 01/2020 and 02/2021, we examined clinical outcomes of pts reassessed post COVID-19 recovery. Results: Among 1557 COVID-19 survivors, 234 (15%) reported sequelae including respiratory symptoms (49.6%), fatigue (41%) and cognitive/psychological dysfunction (4.3%). Persisting COVID-19 sequelae were more likely found in males (p=0.0407) aged ≥65 years (p=0.0489) with ≥2 comorbidities (p=0.0006) and positive smoking history (p=0.0004). Sequelae were associated with history of prior hospitalisation (p<0.0001), complicated disease (p<0.0001) and COVID-19 therapy (p=0.0002). With a median post-COVID-19 follow up of 128 days (95%CI 113-148), multivariable analysis of survival revealed COVID-19 sequelae to be associated with an increased risk of death (HR 1.76, 95%CI 1.16-2.66) after adjusting for sex, age, comorbidities, tumour characteristics, anticancer therapy and COVID-19 severity. Out of 473 patients who were on systemic anticancer therapy (SACT) at COVID-19 diagnosis;62 (13.1%) permanently discontinued therapy and 75 (15.8%) received SACT adjustments, respectively. Discontinuations were due to worsening performance status (45.1%), disease progression (16.1%) and residual organ disfunction (6.3%). SACT adjustments were pursued to avoid hospital attendance (40%), prevent immunosuppression (57.3%) or adverse events (20.3%). Multivariable analyses showed permanent discontinuation to be associated with an increased risk of death (HR 4.2, 95%CI: 1.62-10.7), whereas SACT adjustments did not adversely affect survival. Conclusions: Sequelae post-COVID-19 affect up to 15% of patients with cancer and adversely influence survival and oncological outcomes after recovery. SACT adjustments can be safely pursued to preserve oncological outcomes in patients who remain eligible to treatment. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: A. Cortellini: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Astellas;Financial Interests, Personal, Advisory Board: Sun Pharma. D.J. Pinato: Financial Interests, Personal, Advisory Board: ViiV Healthcare;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Eisai;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca. All other authors have declared no conflicts of interest.
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Background: Despite high contagiousness and rapid spread, SARS-Cov-2 has led to heterogeneous outcomes across affected nations. Within Europe, the United Kingdom is the most severely affected country, with a death toll in excess of 100.000 as of February 2021. We aimed to compare the national impact of Covid19 on the risk of death in UK cancer patients versus those in continental Europe (EU). Methods: We performed a retrospective analysis of the OnCovid study database, a European registry of cancer patients consecutively diagnosed with Covid-19 in 27 centres from February 27 to September 10, 2020. We analysed case fatality rates and risk of death at 30 days and 6 months stratified by region of origin (UK versus EU). We compared patient characteristics at baseline, oncological and Covid-19 specific therapy across cohorts and tested these in multivariable Cox regression models to identify predictors of adverse outcome in UK versus EU patients. Results: Compared to EU patients (n = 924), UK patients (n = 468) were characterised by higher case fatality rates (40.38% versus 26.5%, p < 0.0001), higher risk of death at 30 days (hazard ratio, HR 1.64 [95%CI 1.36-1.99]) and 6 months after Covid-19 diagnosis (47.64% versus 33.33%, p < 0.0001, HR 1.59 [95%CI 1.33-1.88]). UK patients were more often males, of older age and more co-morbid than EU counterparts (p < 0.01). Receipt of anti-cancer therapy was lower in UK versus EU patients (p < 0.001). Despite equal proportions of complicated Covid-19, rates of intensive care admission and use of mechanical ventilation, UK cancer patients were less likely to receive anti-Covid-19 therapies including corticosteroids, anti-virals and interleukin-6 antagonists (p < 0.0001). Multivariable analyses adjusted for imbalanced prognostic factors confirmed the UK cohort to be characterised by worse risk of death at 30 days and 6 months, independent of patient's age, gender, tumour stage and status, number of co-morbidities, Covid-19 severity, receipt of anti-cancer and anti-Covid-19 therapy. Rates of permanent cessation of anti-cancer therapy post Covid-19 were similar in UK versus EU. Conclusions: UK cancer patients have been more severely impacted by the unfolding of the Covid-19 pandemic despite societal risk mitigation factors and rapid deferral of anti-cancer therapy. The increased frailty of UK cancer patients highlights high-risk groups that should be prioritised for anti-SARS-Cov-2 vaccination. Continued evaluation of long-term outcomes is warranted.
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Inflammation is an established driver of severe SARS-CoV-2 infection and a mechanism linked to the increased susceptibility to fatal COVID-19 demonstrated by patients with cancer. As patients with cancer exhibit a higher level of inflammation compared with the general patient population, patients with cancer and COVID-19 may uniquely benefit from strategies targeted at overcoming the unrestrained pro-inflammatory response. Targeted and non-targeted anti-inflammatory therapies may prevent end-organ damage in SARS-CoV-2-infected patients with cancer and decrease mortality. Here, we review the clinical role of selective inhibition of pro-inflammatory interleukins, tyrosine kinase modulation, anti-tumor necrosis factor agents, and other non-targeted approaches including corticosteroids in their roles as disease-modulating agents in patients with COVID-19 and cancer. Investigation of these therapeutics in this highly vulnerable patient group is posited to facilitate the development of tailored therapeutics for this patient population, aiding the transition of systemic inflammation from a prognostic domain to a source of therapeutic targets.
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COVID-19 , Neoplasms , Anti-Inflammatory Agents , Humans , Inflammation , SARS-CoV-2ABSTRACT
Background: The prospective, multicenter, observational INVIDIa-2 study was designed to investigate the clinical efficacy of influenza vaccination in advanced cancer patients receiving immune checkpoint inhibitors (ICIs) from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until April 30, 2020. All ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the INVIDIa-2 study prospectively recorded all the COVID-19 ILI events. Methods: Patients were included in this non-prespecified COVID-19 preliminary analysis if potentially exposed to Sars-Cov-2 infection, namely alive on January 31, 2020, when the Italian government declared the National emergency. The incidence of confirmed COVID-19 was assessed among patients with ILI symptoms, describing the hospitalization rate and mortality. Cases with clinicalradiological diagnosis of COVID-19 without laboratory confirmation (COVID-like ILIs), were also reported. The COVID-incidence was exploratively compared basing on influenza vaccination. Results: 1260 patients receiving ICI were enrolled between October 2019 and January 2020;955 patients were analyzed according to the inclusion criterion. Of them, 66 patients had ILI from January 31, to April 30, 2020. 9 were COVID-19 ILIs with laboratory test confirmation. The COVID-19 ILI incidence was 0.9% (9/955 cases), with hospitalization rate of 100% and mortality rate of 67%. Including 5 COVID-like ILIs, the overall COVID-19 incidence was 1.5% (14/955), with hospitalization in 100% of cases and mortality rate of 64%. COVID-19 incidence was 1.2% for patients vaccinated against influenza (6/482 cases) and 1.7%, among unvaccinated patients (8/473 including 3 confirmed COVID-19 and 5 COVID-like), p = 0.52. The difference was not statistically significant, and the clinical trend in favor of vaccinated patients was lost when considering only confirmed COVID-19 (1.2% in vaccinated vs 0.6% in unvaccinated patients, p = 0.33), probably due to the greater presence of male and elderly patients in the vaccinated group (p = 0.009). Conclusions: We obtained the first prospective epidemiological data about symptomatic COVID-19 in advanced cancer patients receiving ICIs. The overall symptomatic COVID-incidence is meaningful, requiring hospitalization in all cases and leading to a high mortality rate, likely due advanced cancer more than to ICI therapy [Mengyuan Dai, Cancer Discov 2020].
ABSTRACT
Background: At the last update of the TERAVOLT registry, patients with thoracic malignancies and COVID-19showed a high mortality rate (35.5% overall and 31% due to COVID-19) compared to the general population and toother solid tumors. Major determinants of mortality were age, Eastern Cooperative Oncology Group PerformanceStatus (ECOG-PS), and previous administration of chemotherapy. No cancer-specific data are available with respectto small-cell lung cancer (SCLC) and other rare thoracic malignancies. Methods: TERAVOLT is an international, multicenter observational registry launched to collect data on patients withthoracic malignancies diagnosed with COVID-19 infection. Risk factors for hospitalization and mortality wereidentified by Wilcoxon rank sum tests (continuous variables) or χ2 tests (categorical variables). Here we present thesubgroup analyses of SCLC and other rare thoracic malignancies, including malignant pleural mesothelioma (MPM), thymic carcinoma/thymoma, and carcinoid/neuroendocrine lung tumors. Results: As of June 4th, 2020, a total of 581 patients with COVID-19 and thoracic cancers have been entered;among them, 66 (11%) were SCLC, 22 (4%) were MPM, 18 (3%) were thymic carcinoma/thymoma, 12 (2%) werecarcinoid/neuroendocrine lung tumors, and 442 (76%) NSCLC;21 were an unknown type. Among SCLC patients,54% were > 65 years old, 56% were males, 98% were current/former smokers, 31% had an ECOG-PS ≥ 2, 67%had stage IV disease, 82% were on current oncologic treatment at the COVID-19 diagnosis, and 58% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Among other non-NSCLCpatients, 56% were > 65 years old, 56% were males, 69% were current/former smokers, 24% had an ECOG-PS ≥ 2,50% had stage IV disease, 52% were on current oncologic treatment at the COVID-19 diagnosis, and 37% werereceiving chemotherapy alone or in combination with immune checkpoint inhibitors. Overall, 79.7% of the patientsrequired hospitalization, 15.4% were admitted to an ICU, and 39.8% died (36.2% due to COVID-19). Among SCLCpatients, 74.2% required hospitalization, 14.3% were admitted to an ICU, and 42.2% died (37.5% due to COVID-19).Among SCLC patients, age > 65 years old (p=0.81), gender (p=0.71), smoking status (p=1.0), ECOG-PS ≥2(p=0.17), disease stage of IV (p=0.37), and having received chemotherapy alone or with checkpoint inhibitors(p=0.84) were not associated with mortality. Conclusions: This analysis confirmed that patients with thoracic malignancies have a high mortality and risk forhospitalization due to COVID-19 overall. SCLC patients showed the highest mortality rate among thoracic cancerpatients.