The temporal evolution in disease phenotype of COVID-19 hospitalisation, intensive care and case fatality rates in cancer patients across the United Kingdom (UKCCP)

Background: People living with cancer are reported to be at increased risk of hospitalization and death following infection with acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This is proposed to be dependent on a combination of intrinsic patient and cancer factors such as cancer subtype, and emerging SARS-CoV-2 variants with differing pathogenicity. However, COVID-19 phenotype evolution across the pandemic from 2020 has not yet been systematically evaluated in cancer patients. Method(s): This study is a population-scale real-world evaluation of Coronavirus outcomes in the United Kingdom for cancer patients from 1st November 2020-31st August 2022. The cancer cohort comprises individuals from Public Health England's national cancer dataset, excluding individuals less than 18 years old. Case-outcome rates, including hospitalization, intensive care and casefatality rates were used to assess the evolution in disease phenotype of COVID-19 in cancer patients. Multivariable logistic regression models were fitted to compare risk of Coronavirus outcomes in the cancer cohort relative to the non-cancer population during the Omicron wave in 2022. Result(s): The cancer cohort comprised of 198,819 positive SARS-CoV-2 tests from 127,322 individual infections. Coronavirus case-outcome rates were evaluated by reference to 18,188,573 positive tests from 15,801,004 individual infections in the non-cancer population. From 2020 to 2022, the SARS-CoV-2 disease phenotype became less severe in both patients with cancer and the non-cancer population, though cancer patients remain at higher risk. In 2022, the relative risk of Coronavirus hospital admission, inpatient hospitalization, intensive care admission and mortality in cancer patients was 3.02x, 2.10x, 2.53x and 2.54x compared to the non-cancer population following multivariable adjustment, respectively. Higher risk of hospital admission and inpatient hospitalization were associated with receipt of B/T cell antibody and/or targeted therapy which also corresponded with an increased risk of Coronavirus mortality. Conclusion(s): The disease phenotype of SARS-CoV-2 in cancer patients in 2022 has evolved significantly from the disease phenotype in 2020. Direct effects of the virus in terms of SARS-CoV-2 hospitalization, intensive care and case fatality rates have fallen significantly over time. However, relative to the general population, people living with cancer and hematological malignancies remain at elevated risk. In order to mitigate the indirect effects of the SARS-CoV-2 pandemic in terms of disruption to cancer care, there should be increased focus on preventative measures. Used in conjunction with vaccination and early treatment programs, this will maximize quality of life for those with cancer during the ongoing pandemic and ensure the best cancer outcomes.

Real-world outcomes in patients treated with trametinib for low grade serous ovarian carcinoma

Background: In the UK, trametinib (T) is recommended for the treatment of recurrent or progressive low grade serous ovarian cancer (LGSOC) following endocrine therapy (ET) and at least one platinum (Plat) based chemotherapy (ChT) regimen, as an alternative to cytotoxic ChT under interim COVID-19 arrangements. Methods: We conducted a multicentre retrospective study of patients (pts) treated with T in the UK. Eligible pts were adults with recurrent LGSOC who commenced T prior to November 2020. Results: Twenty-eight pts were included (median age 53.5, 19-75). 93% had stage 3-4 disease at presentation. Prior to commencing T, pts received a median of 1.5 lines of ChT (range 0-8) and 1 line (0-3) of ET. Four pts had received ≥3 lines of ChT. Thirty-six per cent had platinum resistant disease (relapse <6 months from last Plat ChT). Median follow up from start of T was 7.1 months (m). Median duration of treatment was 5.0m. Best response was partial response (PR) in 21%, stable disease (SD) in 32%, progressive disease (PD) in 36% and unavailable in 11%. 46% remain on T, 18% are on a subsequent systemic therapy and 29% have died. Treatment was stopped due to PD in 36%, at a median time of 4m. Duration of T therapy was longer in pts without prior Plat resistance (p=0.0219), though response was not significantly associated with Plat sensitivity (p=0.0716). Grade (G) 1-4 adverse events (AEs) were reported in 96% of pts (Table), with 46% experiencing ≥3 AEs. G3-4 AEs occurred in 29%. There were no treatment-related deaths. The most common AEs were skin toxicity (79%), diarrhoea (50%), nausea/vomiting (54%) and fatigue (36%). Treatment was stopped due to toxicity in 5 pts 18% and dosing was interrupted in 19 pts 68%. Ten pts (36%) required a dose reduction (DR), of whom 2 required a further DR. [Formula presented]. Conclusions: T is a safe and effective treatment for LGSOC, with a similar real-world response rate to that reported in GOG 0281. Low-grade toxicities were common, particularly of the skin or gastrointestinal tract, but serious toxicities were uncommon. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: R. Shotton: Financial Interests, Personal, Sponsor/Funding: Servier. M. Randhawa: Non-Financial Interests, Invited Speaker: Bayer;Non-Financial Interests, Institutional, Other, Free drug donation: GSK. S. Williams: Financial Interests, Personal, Other, Consultancy fees: Clovis;Financial Interests, Personal, Other, Consultancy fees: GSK;Financial Interests, Personal, Funding: AstraZeneca. R.M. Glasspool: Financial Interests, Personal and Institutional, Invited Speaker, Advisory Board and Speaker fees;Site PI for commercially sponsored trials: AstraZeneca;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal and Institutional, Other, Advisory Board and Speaker fees, investigator initiated trial grant;Site PI for commercially sponsored trial: Clovis;Financial Interests, Personal, Other, Advisory Board, speaker fees and funding to attend medical conferences;Site PI for commercially sponsored trials: GSK/Tesaro;Financial Interests, Personal, Other, Consultancy fees: Sotio;Financial Interests, Personal and Institutional, Other, Advisory board;Site PI for commercially sponsored trials: Immunogen;Financial Interests, Institutional, Other, Investigator Initiated Trial Grant: Boehringer Ingelheim;Financial Interests, Institutional, Other, Investigator Initiated Trial Grant and Site PI for commercially sponsored trial: Lilly/Ignyta;Non-Financial Interests, Personal, Leadership Role: NCRI Ovarian Group;Non-Financial Interests, Personal, Leadership Role: SGCTG Ovarian;Non-Financial Interests, Personal, Member: IGCS Council;Non-Financial Interests, Personal, Member: ESMO Gyn Cancer Faculty;Non-Financial Interests, Personal, Leadership Role: GCIG Meta-Analysis Group Chair;Non-Financial Interests, Personal, Leadership Role: ENGOT Early Phase;Non-Financial Interests, Personal, Advisory Board: Target Ovarian Cancer;Non-Financial Inte ests, Personal, Member: Horizons Study Expert Panel. C. Gourley: Financial Interests, Personal and Institutional, Research Grant: Novartis. A.R. Clamp: Financial Interests, Personal, Other, Research funding, speaker fees, advisory board: AstraZeneca;Financial Interests, Personal, Other, Speaker fees, advisory board: Clovis Oncology;Financial Interests, Personal, Other, Speaker fees, advisory board: GSK;Financial Interests, Personal, Other, Speaker fees, advisory board: Eisai. G.C. Jayson: Financial Interests, Personal, Research Grant: AstraZeneca. All other authors have declared no conflicts of interest.