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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: Estrogen receptors (ER) are predictive of endocrine responsiveness. However, 30% of ER+ BC patients will relapse despite adjuvant ET and 10 to 20% of metastatic lesions loose the expression of ER. The early identification of endocrine resistant patients may help to improve treatment strategies, especially in the light of innovative drugs recently approved. In the ET-FES trial we evaluated 18F-FES CT/PET as a prediction tool for endocrine responsiveness in ER+ MBC. The ET-FES study was funded by the ERANET-Transcan project. Methods: MBC patients with ER+/HER2- disease, were eligible for the ET/FES study. All patients underwent a baseline [18]F-FES PET/CT in addition to conventional procedures. Patients were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2 and received ET;patients with SUV <2 were randomized to receive ET or chemotherapy (CT). The prognostic role of [18]F-FES PET/CT was assessed for PFS and OS by univariate and multivariate analyses. The primary endpoint was disease progression rate (DPR) at 6 months. Results: From April 2015 to October 2020 146 patients, from 7 EU centers were enrolled: of them, 115 with a mean SUV >2 received ET and 30 with SUV <2 were included in the randomized study. Median follow up was 18.4 months (range 8.0 to 38.3 months) in endocrine sensitive patients (SUV > 2) versus 10.1 months (range 8.0 to 36.8) in patients with SUV <2. Overall, at the time of this analysis 67 patients (45.9%) had disease progression and 37 (25.3%) died. DPR at 6 months was 57% in patients with SUV >2 vs 50% in SUV <2 randomized to ET and 57% in case of CT. DPR at 12 months was 35% vs 17% and 14%, respectively. Median PFS was 7.3 months (IQR 3.8 – 17.3) vs 5.2 (IQR 3.1 – 9.4) vs 7.7 months (IQR 3.0 – 14.0), respectively. OS rate at 12 months was 31% versus 17% versus 14%. Conclusions: The ET-FES clinical trial was prematurely interrupted, due to COVID-19 pandemic. The discriminating ability of this assay was high, leading to a personalized endocrine approach;a considerable proportion of patients with a mean SUV >2 is still on ET. Clinical trial identification: EudraCT 2013-000287-29. Legal entity responsible for the study: Alessandra Gennari - Università del Piemonte Orientale. Funding: AIRC. Disclosure: All authors have declared no conflicts of interest.
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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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We sought to determine parameters of the acute phase response, a feature of innate immunity activated by infectious noxae and cancer, deranged by Covid-19 and establish oncological indices' prognostic potential for patients with concomitant cancer and Covid-19. Between 27/02 and 23/06/2020, OnCovid retrospectively accrued 1,318 consecutive referrals of patients with cancer and Covid-19 aged 18 from the U.K., Spain, Italy, Belgium, and Germany. Patients with myeloma, leukemia, or insufficient data were excluded. The neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), prognostic nutritional index (PNI), modified Glasgow prognostic score (mGPS), and prognostic index (PI) were evaluated for their prognostic potential, with the NLR, PLR, and PNI risk stratifications dichotomized around median values and the pre-established risk categorizations from literature utilized for the mGPS and PI. 1,071 eligible patients were randomly assorted into a training set (TS, n=529) and validation set (VS, n=542) matched for age (67.9±13.3 TS, 68.5±13.5 VS), presence of 1 comorbidity (52.1% TS, 49.8% VS), development of 1 Covid-19 complication (27% TS, 25.9% VS), and active malignancy at Covid-19 diagnosis (66.7% TS, 61.6% VS). Among all 1,071 patients, deceased patients tended to categorize into poor risk groups for the NLR, PNI, mGPS, and PI (P<0.0001) with a return to pre-Covid-19 diagnosis NLR, PNI, and mGPS categorizations following recovery (P<0.01). In the TS, higher mortality rates were associated with NLR>6 (44.6% vs 28%, P<0.0001), PNI<40 (46.6% vs 20.9%, P<0.0001), mGPS (50.6% for mGPS2 vs 30.4% and 11.4% for mGPS1 and 0, P<0.0001), and PI (50% for PI2 vs 40% for PI1 and 9.1% for PI0, P<0.0001). Findings were confirmed in the VS (P<0.001 for all comparisons). Patients in poor risk categories had shorter median overall survival [OS], (NLR>6 30 days 95%CI 1-63, PNI<40 23 days 95%CI 10-35, mGPS2 20 days 95%CI 8-32, PI2 23 days 95%CI 1-56) compared to patients in good risk categories, for whom median OS was not reached (P<0.001 for all comparisons). The PLR was not associated with survival. Analyses of survival in the VS confirmed the NLR (P<0.0001), PNI (P<0.0001), PI (P<0.01), and mGPS (P<0.001) as predictors of survival. In a multivariable Cox regression model including all inflammatory indices and pre-established prognostic factors for severe Covid-19 including sex, age, comorbid burden, malignancy status, and receipt of anti-cancer therapy at Covid-19 diagnosis, the PNI was the only factor to emerge with a significant hazard ratio [HR] in both TS and VS analysis (TS HR 1.97, 95%CI 1.19-3.26, P=0.008;VS HR 2.48, 95%CI 1.47- 4.20, P=0.001). We conclude that systemic inflammation drives mortality from Covid-19 through hypoalbuminemia and lymphocytopenia as measured by the PNI and propose the PNI as the OnCovid Inflammatory Score (OIS) in this context.
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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.
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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: There is uncertainty as to the contribution of cancer patients' features on severity and mortality from Covid-19 and little guidance as to the role of anti-cancer and anti-Covid-19 therapy in this population. Method(s): OnCovid is a retrospective observational study conducted across 19 European centers that recruited cancer patients aged >18 and diagnosed with Covid-19 between 26/02 and 01/04/2020. Uni- and multivariable regression models were used to evaluate predictors of Covid-19 severity and mortality. Result(s): We identified 890 patients from UK (n=218, 24%), Italy (n=343, 37%), Spain (n=323, 36%) and Germany (n=6, 1%). Most patients were male (n=503, 56%) had a diagnosis of solid malignancy (n=753, 84%) and 556 (62%) had active disease. Mean (+/-SD) patient age was 68+/-13 years, and 670 (75%) had >1 co-morbidity, most commonly hypertension (n=386, 43%). Commonest presenting symptoms were fever (n=569, 63%) and cough (n=448, 50%), beginning 6.3 (+/-9.5 SD) days before diagnosis. Most patients (n=565, 63%) had >1 complication from Covid-19, including respiratory failure (n=527, 59%) and acute respiratory distress syndrome (n=127, 22%). In total, 110 patients (14%) were escalated to high-dependency or intensive care. At time of analysis, 299 patients had died (33%). Multi-variate logistic regression identified male gender, age>65 (p<0.0001) presence of >2 comorbidities (p=0.001) active malignancy (p=0.07) as predictors of complicated Covid-19. Mortality was associated with active malignancy (p<0.0001), age>65 and co-morbid burden (p=0.002). Provision of chemotherapy, targeted therapy or immunotherapy was not associated with higher mortality. Exposure to anti-malarials alone (chloroquine/hydroxychloroquine, n=182, p<0.001) or in combination with anti-virals (n=195, p<0.001) or tocilizumab (n=51, p=0.004) was associated with improved mortality compared to patients who did not receive any of these therapies (n=446) independent of patients' gender, age, tumour stage and severity of Covid-19. Conclusion(s): This study highlights the clinical utility of demographic factors for individualized risk-stratification of patients and supports further research into emerging anti Covid-19 therapeutics in SARS-Cov-2 infected cancer patients. Clinical trial identification: NCT04393974. Legal entity responsible for the study: Imperial College London. Funding(s): Has not received any funding. Disclosure: D.J. Pinato: Speaker Bureau/Expert testimony: ViiV Healthcare;Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy: MiNa Therapeutics;Advisory/Consultancy: Eisai;Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Research grant/Funding (institution): MSD. All other authors have declared no conflicts of interest.Copyright © 2020 European Society for Medical Oncology
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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.
Subject(s)
COVID-19 , Neoplasms , Anti-Inflammatory Agents , Humans , Inflammation , SARS-CoV-2ABSTRACT
Introduction or background: During COVID-19 outbreak, helmet noninvasive ventilation (hNIV) and helmet continuous positive airway pressure (hCPAP) have been used with the purpose of early supporting patients with acute respiratory distress syndrome (ARDS) considering the frequent lack of Intensive Care Units (ICU) beds. Rimini province is one of the Italian areas more severely affected. In order to face the increasing number of patients needing respiratory support, in our hospital, 11 monitored beds in Infectious Disease Department's negative pressure rooms have been set up. The management of respiratory failure has been entrusted to the pulmonologists. Aims and objectives: The aim of the study is to evaluate the effectiveness of early hNIV/hCPAP used to avoid or to safely postpone intubation while waiting for a bed in ICU. Methods: We evaluated data collected in 59 patients (14 female and 45 male) with COVID-19 related ARDS admitted in Rimini Hospital Infectious Disease Department to be subjected to hCPAP/hNIV. (Table 1). Results: 36/59 patients (61%) treated with hCPAP survived without intubation. 10 patients were declared do not intubate for comorbidities and received hCPAP as a ceiling treatment, 3/10 survived. 16 patients were intubated (13 in election and 3 for complications), 5/16 died in ICU. To date 47/59 patients (79%) are still alive. Conclusions: During COVID-19 outbreak hCPAP avoided intubation for 36/59 (61%) patients, for others 8 the intubation was elective and postponed. Thanks to the early use of hCPAP, 36 ICU beds could be used to treat other patients with ARDS.
ABSTRACT
Background: The severity of SARS-CoV-2 infection (COVID-19) is predicted by advancing age and co-morbidities. The relative contribution of cancer in influencing the course of COVID-19 is poorly understood. We designed the OnCOVID study to investigate natural history of COVID-19 disease in cancer patients. Methods: This retrospective, multi-center observational study conducted across 8 tertiary centers in Europe recruited cancer patients aged >/= 18 and diagnosed with COVID-19 between February 26th and April 1st, 2020. Descriptive statistics, univariable and multivariable Cox regression models were used to assess patient’s main characteristics and to evaluate the factors associated to COVID-19 related mortality. Results: We identified 204 patients from United Kingdom (n=97, 48%), Italy (n=56, 27%) and Spain (n=51, 25%). Most patients were male (n=127, 62%) had a diagnosis of solid malignancy (n=184, 91%) and 103 (51%) had non-metastatic disease. Mean (±SD) patient age was 69±13 years, and 161 (79%) had >/= 1 co-morbidity, most commonly hypertension (n=88, 43%) and diabetes (n=46, 23%). Commonest presenting symptoms were fever (n=136, 67%) and cough (n=119, 58%), beginning 3.8 (±4.5 SD) days before diagnosis. Most patients (n=141, 69%) had >/= 1 complication from COVID-19, including respiratory failure (n=128, 63%) and acute respiratory distress syndrome (n=49, 24%). In total, 36 patients (19%) patients were escalated to high-dependency or intensive care. At time of analysis, 59 patients had died (29%), 53 were discharged from hospital (26%) and 92 (45%) were in-hospital survivors. Mortality was higher in patients aged >/= 65 (36% versus 16%), in those with >/= 2 co-morbidities (40% versus 18%) and developing >/= 1 complication from COVID-19 (38% versus 4%, p=0.004). Multi-variable analyses confirmed age >/= 65 and >/= 2 co-morbidities to predict for patient mortality independent of tumor stage, active malignancy or anti-cancer therapy. Conclusions: In the early outbreak of SARS-CoV-2 infection in Europe co-morbid burden and advancing age predicted for adverse disease course in cancer patients. Risk stratification based on these factors should inform personalized oncological decision making during the COVID-19 pandemic. Legal entity responsible for the study: Imperial College London. Funding: Has not received any funding. Disclosure: D.J. Pinato: Speaker Bureau/Expert testimony, received lecture fees : ViiV Healthcare;Speaker Bureau/Expert testimony, received lecture fees : Bayer Healthcare;Travel/Accommodation/Expenses: BMS;Advisory/Consultancy: Mina Therapeutics;EISAI;Roche;Astra Zeneca;Research grant/Funding (institution): MSD;BMS. A. Patriarca: Advisory/Consultancy: Takeda;Sanofi. G. Gaidano: Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen;Abbvie;Advisory/Consultancy: AstraZeneca;Sunesys. J. Brunet: Advisory/Consultancy: MSD;AstraZeneca. J. Tabernero: Advisory/Consultancy: Array Biopharma;Astra Zeneca;Bayer;Beigene;Boehringer Ingelheim;Chugai;Genentech;GenMab;Halozyme;Inflection Biosciences Limited;Ipsen;Kura;Lilly;MSD;Menarini;Merck Serono;Merrimack;Merus;Molecular Partners;Novartis;Peptomics;Pfizer;Pharmacyclics;Rafael Pharmaceuticals;ProteoDesign SL;F. Hoffmann-La Roche Ltd;Sanofi;Servier;Seagen;Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. A. Prat:Honoraria (self), Advisory/Consultancy: Pfeizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis;Roche;Honoraria (self): MSD Oncology;Lilly;Honoraria (self), Travel/Accommodation/Expenses: Daiichi Sankyo;Advisory/Consultancy: BMS;Amgen;NanoString Technologies. A. Gennari: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche;Eli Lilly;EISAI;Advisory/Consultancy: Pierre Fabre;MSD;Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Daiichi Sankyo;Speaker Bureau/Expert testimony: Teva;Gentili;Pfizer;AstraZeneca;Celgene. All other authors have declared no onflicts of interest.