ABSTRACT
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.
ABSTRACT
Background: Immune checkpoint inhibitors targeting PD-1 and PD-L1 have significantly impacted treatment of Non-Small Cell Lung Cancer (NSCLC). KEYNOTE-189 demonstrated first-line pembrolizumab plus pemetrexed-platinum improves progressionfree survival (PFS) and overall survival (OS) in metastatic nonsquamous NSCLC, regardless of tumour PD-L1 expression [1]. Translating evidence from trials to real-world patient populations can be challenging as a significant proportion of patients in daily practice are often under-represented in randomised control trials due to strict inclusion and exclusion criteria. We aimed to compare real-world data with outcomes from KEYNOTE-189. Methods: We performed a retrospective analysis of 56 patients with metastatic nonsquamous NSCLC without targetable mutations, treated with first line pembrolizumab, pemetrexed and platinum. Data were collected from electronic records between October 2018 and January 2021 in 2 London cancer centres. Results: Our cohort comprised 56 patients with median age 61 years, 75% with smoking history, 59% male and 41% female. PD-L1 expression was <1% in 57% of patients. Median follow-up was 8.7 months. All patients received at least one cycle and 53% completed 4 cycles of chemoimmunotherapy. Treatment was stopped early or pemetrexed maintenance treatment was omitted due to COVID-19 in 4 patients (7%). Median PFS was 7.1 months (range 1.8 to 26.3) and median OS was 8.7 months (range 1.8 to 26.3). OS at 12 months was reached by 21 patients (38%). Adverse events were observed in 30 patients (54%), including grade 3-5 adverse events in 15 patients (27%). Conclusions: Median PFS was similar in our cohort compared to KEYNOTE-189, but not as substantial as that reported in their updated analysis. OS was lower in our cohort, however a significant proportion of our patients recently commenced treatment and had shorter duration follow-up. Safety outcomes were superior in our cohort compared to KEYNOTE-189. Disclosure: No significant relationships.
ABSTRACT
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.
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.