ABSTRACT
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
ABSTRACT
Introduction: Older adults comprise an increasing proportion of emergency general surgery (EGS) admissions and face high morbidity and mortality. We created a geriatric surgical service with geriatric and palliative expertise to mitigate risks of hospitalization most hazardous to older patients. In this study, we identified geriatric surgical service interventions most relevant to EGS patients. Methods: We conducted a retrospective chart review of patients >75 years admitted to the EGS service at our urban tertiary care hospital with a score >3 by the FRAIL scale, a five-point frailty screening instrument, or history of dementia. The geriatric surgical service, led by a dually-board certified geriatric and palliative care specialist, consulted on these patients from January 2020-January 2021;a hiatus was taken for the COVID-19 pandemic. Consults included a comprehensive geriatric assessment and calculated a modified Rockwood Frailty Index. Hospital admission characteristics and consultation components were collected via chart review. Results: Forty patients were evaluated (median age 82 years (IQR 78-89), 55.0% female). The most common admission diagnosis was small bowel obstruction (32.5%). 62.5% of patients underwent >1 surgical procedure. Median time to geriatric consult from admission was 3 days (IQR 1.0-4.3). By Frailty Index, 58% were moderately or severely frail. Interventions included medication changes (97.5%), symptom management (82.5%), delirium prevention and management (65.0%), mobility and function recommendations (65.0%), serious illness conversations (55.0%), and code status change (17.5%). Conclusion: Geriatric service involvement identifies and addresses a high burden of both geriatric and palliative care needs in older adult EGS patients.
ABSTRACT
Introduction: Before the COVID-19 pandemic, 20-30% of family members had symptoms of Post-Traumatic Stress Disorder (PTSD) or anxiety, while 15-30% had symptoms of depression. Interventions supporting family members have reduced burden of these symptoms. COVID-19 has resulted in prolonged ICU stays, high morbidity/mortality, and hospital policies severely limiting family presence at the bedside. We hypothesized the combination of prolonged critical illness and the necessary reduction of family presence would lead to high rates of PTSD, anxiety, and depression;likely higher than observed in previous studies. Methods: This was a multicenter study including 12 US hospitals, 8 academic and 4 community-based hospitals. A consecutive sample of family members of all patients with COVID-19 receiving ICU admission during the spring US peak in 2020 were called 3-4 months after the patients' ICU admission, except for New York City hospitals where a random sample was generated given the large number of hospitalizations. Consented participants completed the Impact-of- Events Scale-6 (IES-6;scored 0-30, higher scores indicate more symptoms of PTSD), Hospital-Anxiety- Depression Score (HADS, scored 0-20 for anxiety and 0-20 for depression, higher scores indicate more symptoms), and a subset of questions from Family-Satisfaction in the ICU-27 (FS-ICU27;scored on a Likert scale 1 to 5, with higher scores indicating more positive responses) selected as most likely impacted by restrictive family presence.Results: There were 945 eligible family members during the study period. Of those, 594 were contacted and 269 (45.3%) consented and completed surveys. The mean IES-6 score was 12.6 (95% CI 11.8- 13.4) with 65.4% having a score of 10 or greater, consistent with high levels of symptoms of PTSD. The mean score on the HADS-anxiety was 9.4 (95% CI 8.8-10.1) with 59.5% having a score of 8 or greater, consistent with high levels of symptoms of anxiety. Finally, the mean score for the HADS-depression was 8.0 (95% CI 7.3-8.7) with 47.6% having scores of 8 or greater, consistent with high level of symptoms of depression. The mean response for the FSICU27 questions of “I felt I had control” was 3.5 (95% CI 3.3-3.6), “I felt supported” was 3.8 (95% CI 3.6-4.0), and “I felt included” was 4.3 (95% CI 4.2-4.4).Conclusion: The consequences of a family member admitted to the ICU with COVID-19 infection are significant. We identify rates of PTSD, anxiety, and depression higher than recorded in non-COVID population. Further analysis is warranted to understand modifiable risk factors for developing these symptoms.