COLUMBIA-1: A phase Ib/II, open-label, randomized, multicenter study of durvalumab plus oleclumab in combination with chemotherapy and bevacizumab as first-line (1L) therapy in metastatic microsatellite-stable colorectal cancer (MSS-mCRC)

Background: Despite advances in the treatment of mCRC combining chemotherapy regimens with biologics, most patients (pts) still progress within 11 months of receiving 1L chemotherapy. Addition of novel therapies to the standard of care (SoC) to improve antitumor activity is urgently needed. The randomized part 2 of COLUMBIA-1 (NCT04068610) evaluated the safety and efficacy of combining SoC (bevacizumab [BEV] + FOLFOX) with the PD-L1 inhibitor durvalumab (D) and the anti-CD73 monoclonal antibody oleclumab (O). Method(s): Pts with previously untreated, MSS-mCRC and ECOG PS <=1 received either SoC alone or SoC + D (1500 mg, Q4W) + O (3000 mg Q2W x4 then Q4W) in the experimental arm (EXP). The primary endpoint was objective response rate (ORR) per investigator assessed RECIST v1.1. Result(s): As of 10 Dec 2021, 52 pts were enrolled, of whom 51 were response evaluable. The confirmed ORR with SoC was 44.0% (95% confidence interval [CI], 24.4-65.1%) compared to 61.5% (95% CI, 40.6-79.8%) in the EXP arm. Median OS was not reached (SoC) vs 19.1 mos (EXP);median PFS was 11.1 mos (SoC) vs 10.9 mos (EXP;Table). Grade >=3 treatment emergent adverse events (TEAEs) occurred in 76.9% of pts in SoC and 65.4% EXP. Fatal TEAEs (all unrelated) were observed in 3 pts in the EXP arm: 1 with sepsis and 2 with intestinal perforation. One pt with intestinal perforation deemed related to BEV experienced fatal peritonitis. In the SoC arm, there was a single fatal COVID-19 TEAE. The most frequent treatment-related AEs in the EXP arm were diarrhea (38.5%), peripheral sensory neuropathy (38.5%) and fatigue (26.9%). There was no identified association between CD73 expression and clinical benefit. Conclusion(s): Addition of D + O to FOLFOX + BEV SoC showed a moderate response increase without PFS benefit vs SoC alone. Safety was consistent with known safety profiles. [Formula presented] Clinical trial identification: NCT04068610. Editorial acknowledgement: Editing support for this , under the direction of the authors, was provided by Catherine Crookes of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding(s): AstraZeneca. Disclosure: N.H. Segal: Financial Interests, Personal, Advisory Board: Immunocore, PsiOxus, Roche/Genentech, BI, Revitope, ABL Bio, Novartis, GSK, AstraZeneca, Numab;Financial Interests, Personal, Research Grant: Regeneron, Immunocore, PureTech, AstraZeneca, BMS, Merck, Pfizer, Roche/Genentech. J. Tie: Financial Interests, Personal, Invited Speaker, Honorarium: Novartis, Amgen, Merck Serono, Merck Sharp and Dohme, Pierre Fabre;Financial Interests, Personal, Advisory Board: Haystack Oncology, Amgen, Novartis, AstraZeneca, Merck Serono, Merck Sharp and Dohme, Pierre Fabre, BMS;Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Pfizer, Daiichi Sankyo, Novartis. S. Kopetz: Financial Interests, Personal, Ownership Interest: MolecularMatch, Lutris, Iylon;Financial Interests, Personal, Research Grant: Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, AstraZeneca, Novartis, Amgen, Lilly, Daiichi Sankyo;Financial Interests, Personal, Other: Genetech, EMD Serono, Merck, Holy Stone, Novartis, Lilly, BI, Boston Biomedical, AstraZeneca, Bayer Health, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Lutris, Jacobio, Pfizer, Repare Therapeutics, Inivata, GSK, Jazz Pharmaceuticals, Iylon, Xilis, AbbVie, Amal Therapeutics, Gilead, Mirati, Flame Biosciences, Servier, Carina Biotechnology, Bicara Therapeutics, Endeavor BioMedicines, Numab Pharma, Johnson and Johnson/Janssen. M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Beigene, MSD, Servier, Pierre Fabre, Amgen;Financial Interests, Personal, Advisory Board: Terumo, Roche, Merck Serono, Bayer, Daiichi Sankyo, Sotio;Financial Interests, Institutional, Research Grant: Keocyt, Roche, Bayer. E. Chen: Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Princip l Investigator: AstraZeneca. R. Dienstmann: Financial Interests, Personal, Speaker's Bureau: Roche, BI, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp and Dohme, Lilly, AstraZeneca;Financial Interests, Personal, Advisory Board: Roche, BI;Financial Interests, Personal, Research Grant: Merck, Pierre Fabre. A. Hollebecque: Financial Interests, Personal, Invited Speaker: Servier, Incyte, EISAI;Financial Interests, Personal, Advisory Board: Basilea, Tahio, Relay Theraeutics, QED Therapeutics, Debiopharm;Financial Interests, Institutional, Funding: Incyte;Financial Interests, Institutional, Research Grant: AstraZeneca;Non-Financial Interests, Personal, Principal Investigator, M19-345: AbbVie;Non-Financial Interests, Personal, Principal Investigator, CO42216: Roche;Non-Financial Interests, Personal, Principal Investigator, MCLA-158: Merus;Non-Financial Interests, Personal, Principal Investigator, SGNB6A: Seattle Genetics;Non-Financial Interests, Personal, Principal Investigator, TAS-120-202: Tahio;Non-Financial Interests, Personal, Principal Investigator, Krystal-10: Mirati;Non-Financial Interests, Personal, Principal Investigator, ADP-0033: Adaptimmune;Non-Financial Interests, Personal, Principal Investigator, ACT16902: Sanofi;Non-Financial Interests, Personal, Principal Investigator, C4201002: Pfizer;Non-Financial Interests, Personal, Principal Investigator, RLY-4008: Relay Therapeutics;Non-Financial Interests, Personal, Principal Investigator, CC-90011: Celgene/BMS;Non-Financial Interests, Personal, Principal Investigator, Loxo-IDH: Loxo/Lilly;Non-Financial Interests, Personal, Principal Investigator: AstraZeneca. M. Reilley: Financial Interests, Personal, Advisory Board: BMS, Helsinn, ZielBio. M.E. Elez Fernandez: Financial Interests, Personal, Invited Speaker: Novartis, Organon;Financial Interests, Personal, Advisory Board: Amgen, Bayer, F. Hoffman La Roche, Merck Serono, MSD, Pierre Fabre, Sanofi, Servier;Financial Interests, Institutional, Funding: Amgen, Array Biopharma, AstraZeneca, BeiGene, BI, BMS, Celgene, Debiopharm International SA, F. Hoffman La Roche, Genentech, HalioDX SAS, Hutchinson MediPharma International, Janssen-Cilag SA, Menarini, Merck ealth KgaA, MSD, Merus NV, Mirati, Novartis Farmaceutica SA, Pfizer, PharmaMar, Sanofi Aventis Recherche & Developpement, Servier, Taiho Pharma;Financial Interests, Personal, Other, ASCO Scientific Program Committee: Developmental Therapeutics - Immunotherapy: ASCO;Financial Interests, Personal, Other, Speaker of the ESMO Academy: ESMO;Financial Interests, Personal, Other, Coordinator of the SEOM +MIR Section of Residents and Young Assistants: SEOM;Financial Interests, Personal, Other, Travel, accommodations, expenses: Amgen, Array BioPharma, BMS, Merck Serono, Roche, Sanofi, Servier. J. Cosaert: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca;Financial Interests, Personal, Member: AstraZeneca. J. Cain: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Hernandez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. N. Hewson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. Z.A. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. M. Dressman: Financial Interests, Personal, Full or part-time Employment: AstraZeneca;Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Tabernero: Financial Interests, Personal, Advisory Role: Array BioPharma, AstraZeneca, Bayer, BI, Chugai, Daiichi Sankyo, F. Hoffman-La Roche Ltd, Genentech, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, Inspirna Inc, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandio Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Tessa Therapeutics, TheraMyc;Financial Interests, Personal, Stocks/Shares: Oniria Therapeutics;Financial Interests, Personal, Other, educational collaboration: Imedex/HMP, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, Physicians Education Resource (PER). Copyright © 2022 European Society for Medical Oncology

Immune checkpoint inhibitor therapy and outcomes from SARS-CoV-2 infection in patients with cancer: A joint analysis of OnCovid and ESMO-CoCARE registries

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

Clinical effectiveness of SARS-CoV-2 vaccines and booster doses in patients with cancer: An analysis from the European OnCovid registry

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.

Clinical assessment of the Omicron outbreak in Europe and trends in morbidity and mortality from COVID-19 and cancer

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.

The acute phase response identifies cancer patients with adverse outcomes from SARS-CoV-2 infection as quantified by the OnCovid Inflammatory Score

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.

The impact of COVID-19 on cancer care and oncology clinical research: an experts' perspective.

The coronavirus disease-19 (COVID-19) pandemic promises to have lasting impacts on cancer clinical trials that could lead to faster patient access to new treatments. In this article, an international panel of oncology experts discusses the lasting impacts of the pandemic on oncology clinical trials and proposes solutions for clinical trial stakeholders, with the support of recent data on worldwide clinical trials collected by IQVIA. These lasting impacts and proposed solutions encompass three topic areas. Firstly, acceleration and implementation of new operational approaches to oncology trials with patient-centric, fully decentralized virtual approaches that include remote assessments via telemedicine and remote devices. Geographical differences in the uptake of remote technology, including telemedicine, are discussed in the article, focusing on the impact of the local adoption of new operational approaches. Secondly, innovative clinical trials. The pandemic has highlighted the need for new trial designs that accelerate research and limit risks and burden for patients while driving optimization of clinical trial objectives and endpoints, while testing is being minimized. Areas of considerations for clinical trial stakeholders are discussed in detail. In addition, the COVID-19 pandemic has exposed the underrepresentation of minority groups in clinical trials; the approach for oncology clinical trials to improve generalizability of efficacy and outcomes data is discussed. Thirdly, a new problem-focused collaborative framework between oncology trial stakeholders, including decision makers, to leverage and further accelerate the innovative approaches in clinical research developed during the COVID-19 pandemic. This could shorten timelines for patient access to new treatments by addressing the cultural and technological barriers to adopting new operational approaches and innovative clinical trials. The role of the different stakeholders is described, with the aim of making COVID-19 a catalyst for positive change in oncology clinical research and eventually in cancer care.

Time-dependent improvement in the clinical outcomes from COVID-19 in cancer patients: An updated analysis of the OnCovid registry

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.

Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients

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

MONEO: A phase II study of avelumab (Av) plus FLOT in the peri-operative treatment for patients (pts) with resectable gastric or gastroesophageal junction cancer (GC)

Background: GC represents a worldwide problem;radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21;ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5 of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study.

Determinants of enhanced vulnerability to Covid-19 in U.K. cancer patients: Results from the OnCovid study

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.

Has COVID-19 had a greater impact on female than male oncologists? Results of the ESMO Women for Oncology (W4O) Survey.

BACKGROUND: European Society for Medical Oncology Women for Oncology (ESMO W4O) research has previously shown under-representation of female oncologists in leadership roles. As early reports suggested disproportionate effects of the COVID-19 pandemic on women, the ESMO W4O Committee initiated a study on the impact of the pandemic on the lives of female and male oncologists. METHODS: A questionnaire was sent to ESMO members and put on the ESMO website between 8 June 2020 and 2 July 2020. Questions focused on the working (hospital tasks, laboratory tasks, science) and home (household management, childcare, parent care, personal care) lives of oncologists during and after COVID-19-related lockdowns. RESULTS: Of 649 respondents, 541 completed the questionnaire. Of these, 58% reported that COVID-19 had affected their professional career, 83% of whom said this was in a negative way (85% of women versus 76% of men). Approximately 86% reported that COVID-19 had changed their personal life and 82% their family life. Women were again significantly more affected than men: personal life (89% versus 78%; P = 0.001); family life (84% versus 77%; P = 0.037). During lockdowns, women reported increased time spent on hospital and laboratory tasks compared with men (53% versus 46% and 33% versus 26%, respectively) and a significantly higher proportion of women than men spent less time on science (39% versus 25%) and personal care (58% versus 39%). After confinement, this trend remained for science (42% versus 23%) and personal care (55% versus 36%). CONCLUSIONS: The COVID-19 pandemic has adversely affected the professional and home lives of oncologists, especially women. Reduced research time for female oncologists may have long-lasting career consequences, especially for those at key stages in their career. The gender gap for promotion to leadership positions may widen further as a result of the pandemic.

Determinants of mortality from SARS-CoV-2 infection in European cancer patients

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.

Influence of recent administration and type of oncological treatment (T) in survival of oncological patients (p) with COVID-19: Experience of Vall d'Hebron University Hospital

Background: SARS-CoV-2 outbreak has impacted on the management of oncological p, leading to treatment delays in a considerable number of cases. The aim of this study was to evaluate if oncological T affected negatively COVID-19 outcome. Methods: We retrospectively analyzed clinical data from p with solid tumors under active systemic T (received in the last 6 months) that were diagnosed with SARS-CoV-2 infection (defined as positive PCR) between March and 11th May 2020 in our center. Study endpoint was death due to COVID-19. We divided the patients in two groups;those who had received treatment in the last 4 weeks and those who had not. Descriptive and univariate analysis were performed to detect the effect of T type and other variables on COVID-19 related mortality. Results: A total of 70 p were included with a median follow-up of 28 days (10-47) and active oncological T had been administered in the past 4 weeks to 44 p. Median age was 66 (IQR 56-74), 23 p (52.27%) were female and 41 (93.2%) had a baseline ECOG≤1. The most frequent primary site was lung tumor (12 p [27.3%]), followed by breast (11 p [25%]) and gastrointestinal (5 p [11.4%]). Thirty-one p (70.5%) had metastatic disease and 13 (29.5%) were included in clinical trials. Twenty-four p (54.5%) received chemotherapy (CT), 14 (31.8%) targeted therapies, 9 (20.4%) immunotherapy (IT), 5 (11.4%) radiotherapy and 6 (13.6%) hormonotherapy. A total of 13 p (29.5%) received different combinations of oncological T. Death due to COVID-19 occurred in 5/22 (22.7%) p receiving CT and 6/21 (28.5%) p in the non-CT (p>0.05). Only 1/9 (11.1%) p treated with IT died compared to 11/35 (31.4%) p in the rest of the cohort (p>0.05). Age>71, comorbidities such as chronic obstructive pulmonary disease and ECOG status>2 were associated to a higher mortality. The distribution of these variables between the anticancer T groups was not different. Conclusions: Our results suggest that CT and other anticancer T might not worsen COVID-19 related mortality;nevertheless, the number of patients was small. and decision making has to be individualized. Our findings may warrant further investigation in larger studies. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: E. Felip: Advisory/Consultancy, Speaker Bureau/Expert testimony: AbbVie;AstraZeneca;Blueprint medicines;Boehringer Ingelheim;Bristol-Myers Squibb;Celgene;Eli Lilly;Guardant Health;Janssen;Medscape;Merck KGaA;Novartis;Pfizer;Roche;Takeda;Touchtime;Research grant/Funding (self), Research grant/Funding (institution): Fundación Merck Salud;Oncology Innovation EMD Serono. J. Carles: Advisory/Consultancy, Speaker Bureau/Expert testimony: Johnson & Johnson;Bayer;Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Astellas Pharma;Advisory/Consultancy: Pfizer;Sanofi;MSD Oncology;Advisory/Consultancy, Research grant/Funding (self): Roche;Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZéneca;Speaker Bureau/Expert testimony: Asofarma;Research grant/Funding (self), Travel/Accommodation/Expenses: BMS;ravel/Accommodation/Expenses: Ipsen;Roche;Research grant/Funding (self): AB Science;Aragon Pharmaceuticals;Pharmaceuticals;INC;Blueprint Medicines Corporation;N Immunotherapeutics INC;Boehringer Ingelheim España, S.A.;Clovis Oncology;Cougar Biotechnology INC;Deciphera Pharmaceuticals LLC;Exelixis INC;F. Hoffmann-La Roche LTD;Genentech INC;Glaxosmithkline;Incyte Corporation;Janssen-Cilag International NV;Karyopharm Therapeutics INC;Laboratoires Leurquin Mediolanum SAS. J. Tabernero: Honoraria (self): Array Biopharma;AstraZeneca;Bayer;BeiGene;Boehringer Ingelheim;Chugai;Genentech;Genmab A/S;Halozyme;Imugene Limited;Inflection Biosciences Limited;Ipsen;Kura Oncology;Lilly;MSD;Merck Serono;Menarini;Merrimack;Merus;Molecular Partners;Novartis;Peptomyc;Pfizer;Pharmacyclics;ProteoDesign SL;Rafael Pharmaceuticals;F. Hoffmann-La Roche Ltd;): Sanofi;eaGen;Seattle Genetics, Servier, Symphogen, Taiho, VCN Biosciences, Biocartis, Foundation Medicine, HalioDX SAS and Roche Diagnostics. All other authors have declared no conflicts of interest.