Compared with previous standards of care (including chemotherapy, radiotherapy, and surgery), cancer immunotherapy has brought significant improvements for patients in terms of survival and quality of life. Immunotherapy has now firmly established itself as a novel pillar of cancer care, from the metastatic stage to the adjuvant and neoadjuvant settings in numerous cancer types. In this review article, we highlight how the history of cancer immunotherapy paved the way for discoveries that are now part of the standard of care. We also highlight the current pitfalls and limitations of cancer checkpoint immunotherapy and how novel research in the fields of personalized cancer vaccines, autoimmunity, the microbiome, the tumour microenvironment, and metabolomics is aiming to solve those challenges.
Introduction Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free units. Nevertheless, the frequency and relevance of nosocomial transmission of COVID-19 in patients with cancer remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify predictive factors for COVID-19 severity in patients with cancer. Methods Patients with cancer and a laboratory-confirmed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3 rd and May 23 rd , 2020 in the provinces of Quebec and British Columbia in Canada. Patient’s baseline characteristics including age, sex, comorbidities, cancer type, and type of anti-cancer treatment were collected. The exposure of interest was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 ≥ 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission and/or mechanical ventilation. Results A total of 252 patients (N=249 adult, and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=233). One-hundred-and-six patients (42.1%) received active anti-cancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 25 days, 33 (13.1%) required admission to the ICU, and 71 (28.2%) died. Forty-seven (19.1%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs unreached, HR 2.3, 95% CI 1.2-4.4, p=0.0006). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Interpretation Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free units. We also validated that age and advanced cancer were negative predictive factors for COVID-19 severity in patients with cancer.
BackgroundPatients with cancer who are infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to develop severe illness and die compared with those without cancer. The impact of immune checkpoint inhibition (ICI) on the severity of COVID-19 illness is unknown. The aim of this study was to investigate whether ICI confers an additional risk for severe COVID-19 in patients with cancer.MethodsWe analyzed data from 110 patients with laboratory-confirmed SARS-CoV-2 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe and Australia. The primary objective was to describe the clinical course and to identify factors associated with hospital and intensive care (ICU) admission and mortality.FindingsThirty-five (32%) patients were admitted to hospital and 18 (16%) died. All patients who died had advanced cancer, and only four were admitted to ICU. COVID-19 was the primary cause of death in 8 (7%) patients. Factors independently associated with an increased risk for hospital admission were ECOG ≥2 (OR 39.25, 95% CI 4.17 to 369.2, p=0.0013), treatment with combination ICI (OR 5.68, 95% CI 1.58 to 20.36, p=0.0273) and presence of COVID-19 symptoms (OR 5.30, 95% CI 1.57 to 17.89, p=0.0073). Seventy-six (73%) patients interrupted ICI due to SARS-CoV-2 infection, 43 (57%) of whom had resumed at data cut-off.InterpretationCOVID-19–related mortality in the ICI-treated population does not appear to be higher than previously published mortality rates for patients with cancer. Inpatient mortality of patients with cancer treated with ICI was high in comparison with previously reported rates for hospitalized patients with cancer and was due to COVID-19 in almost half of the cases. We identified factors associated with adverse outcomes in ICI-treated patients with COVID-19.
Objectives The aim of this study was to compare the efficacy and safety of FOLFIRINOX (5-FU/leucovorin, irinotecan, and oxaliplatin) and gemcitabine/nab-paclitaxel (GnP) in patients with advanced pancreatic cancer. Methods Patients with newly diagnosed advanced pancreatic cancer in Saskatchewan, Canada, from 2011 to 2016, who received FOLFIRINOX or GnP were assessed. A Cox proportional multivariate analysis was performed to evaluate prognostic variables. Results One hundred nineteen eligible patients with median age of 61 years and male/female ratio of 70:49 were identified. Seventy-seven percent had metastatic disease. Of 119 patients, 86 (72%) received FOLFIRINOX and 33 (28%) were treated with GnP. Median progression-free survival of the FOLFIRINOX group was 6.0 months [95% confidence interval (CI), 4.5–7.5] versus 4.0 months (95% CI, 2.9–5.1) with GnP (P = 0.39). The median overall survival of the FOLFIRINOX group was 9.0 months (95% CI, 7–11) compared with 9.0 months (95% CI, 4.2–13.8) with GnP (P = 0.88). On multivariate analysis, albumin [hazard ratio (HR), 0.63; 95% CI, 0.41–0.97], male sex (HR, 0.65; 95% CI, 0.43–0.97), and second-line therapy (HR, 0.50; 95% CI, 0.28–0.86) were correlated with survival. Conclusions Our results showed that real-world patients with advanced pancreatic cancer treated with FOLFIIRNOX or GnP had comparable survival with different safety profile.
Background: ICI are widely used in the treatment of various cancer types. It has been hypothesized that ICI could confer an increased risk of severe acute lung injury or other complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We analyzed data from 113 patients with laboratory-confirmed COVID-19 while on treatment with ICI without chemotherapy in 19 hospitals in North America, Europe, and Australia. Data collected included details on symptoms, comorbidities, medications, treatments and investigations for COVID-19, and outcomes (hospital admission, ICU admission, and mortality). Results: The median age was 63 years (range 27–86); 40 (35%) patients were female. Most common malignancies were melanoma (n=64, 57%), non-small cell lung cancer (n=19, 17%), and renal cell carcinoma (n=11, 10%); 30 (27%) patients were treated for early (neoadjuvant/adjuvant) and 83 (73%) for advanced cancer. Most patients received anti-PD-1 (n=85, 75%), combination anti-PD-1 and anti-CTLA-4 (n=15, 13%), or anti-PD-L1 (n=8, 7%) ICI. Comorbidities included cardiovascular disease (n=31, 27%), diabetes (n=17, 15%), and pulmonary disease (n=14, 12%). Symptoms were present in 68 (60%) patients; 46 (68%) had fever, 40 (59%) cough, and 23 (34%) dyspnea. Overall, ICI was interrupted in 58 (51%) patients. At data cutoff, 33 (29%) patients were admitted to hospital, 6 (5%) to ICU, and 9 (8%) patients died. COVID-19 was the primary cause of death in 7 patients, 3 of whom were admitted to ICU. Cancer types in patients who died were melanoma (2), non-small cell lung cancer (2), renal cell carcinoma (2), and others (3); all (9) patients had advanced cancer. Administered treatments were oxygen therapy (8), mechanical ventilation (2), vasopression (2), antibiotics (7), antiviral drugs (4), glucocorticoids (2), and anti-IL-6 (2). Of all hospitalized patients, 20 (61%) had been discharged and 4 (12%) were still in hospital at data cutoff. Conclusion: The mortality rate of COVID-19 in patients on ICI is higher than rates reported for the general population without comorbidities but may not be higher than rates reported for the cancer population. Despite these preliminary findings, COVID-19 patients on ICI may not have symptoms and a proportion may continue ICI. Correlative analyses are ongoing and will be presented. Citation Format: Aljosja Rogiers, Carlo Tondini, Joe M. Grimes, Megan H. Trager, Sharon Nahm, Leyre Zubiri, Neha Papneja, Arielle Elkrief, Jessica Borgers, April Rose, Johanna Mangana, Michael Erdmann, Ines Pires da Silva, Christian Posch, Axel Hauschild, Lisa Zimmer, Paola Queirolo, Caroline Robert, Karijn Suijkerbuijk, Paolo A. Ascierto, Paul Lorigan, Richard Carvajal, Osama E Rahma, Mario Mandala, Georgina V. Long. Clinical characteristics and outcomes of coronavirus 2019 disease (COVID-19) in cancer patients treated with immune checkpoint inhibitors (ICI) [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S02-01.
Background: Studies suggest that patients with cancer are more likely to experience severe outcomes from COVID-19. Therefore, cancer centers have undertaken efforts to care for patients with cancer in COVID-free zones. Nevertheless, nosocomial transmission of COVID-19 in patients with cancer likely occurs, but the frequency and relevance of these events remain unknown. The goal of this study was to determine the incidence and impact of hospital-acquired COVID-19 in this population and identify prognostic factors for COVID-19 severity in patients with cancer. Methods: Patients with cancer and a laboratory-confirmed or presumed diagnosis of COVID-19 were prospectively identified using provincial registries and hospital databases between March 3rd and May 23rd, 2020, in the provinces of Quebec and British Columbia. Patients’ baseline characteristics including age, sex, comorbidities, cancer type, and type of anticancer treatment were collected. The primary outcome was incidence of hospital-acquired infection defined by diagnosis of SARS-CoV-2 5 days after hospital admission for COVID-unrelated cause. Co-primary outcomes were death or composite outcomes of severe illness from COVID-19 such as hospitalization, supplemental oxygen, intensive-care unit (ICU) admission, and/or mechanical ventilation. Results: A total of 253 patients (N=250 adult and N=3 pediatric) with COVID-19 and cancer were identified, and the majority were residents of Quebec (N=236). Ninety patients (35.6%) received active anticancer treatment in the last 3 months prior to COVID-19 diagnosis. During a median follow-up of 23 days, 209 (82.6%) required hospitalization, 38 (15%) required admission to ICU, and 71 (28%) died. Forty-seven (19%) had a diagnosis of hospital-acquired COVID-19. Median overall survival was shorter in those with hospital-acquired infection, compared to a contemporary community-acquired population (27 days vs. 71 days, HR 2.2, 95% CI 1.2-4.0, p=0.002). Multivariate analysis demonstrated that hospital-acquired COVID-19, age, ECOG status, and advanced stage of cancer were independently associated with death. Conclusion: Our study demonstrates a high rate of nosocomial transmission of COVID-19, associated with increased mortality in both univariate and multivariate analysis in the cancer population, reinforcing the importance of treating patients with cancer in COVID-free zones. We also validated that age, poor ECOG, and advanced cancer were negative prognostic factors for COVID-19 in patients with cancer. Citation Format: Arielle Elkrief, Antoine Desilets, Neha Papneja, Lena Cvetkovic, Catherine Groleau, Yahia Abdelali Lakehal, Layla Shbat, Corentin Richard, Julie Malo, Wiam Belkaid, Erin Cook, Stephane Doucet, Thai Hoa Tran, Patrice Savard, Kevin Jao, Nathalie Daaboul, Eric Bhang, Jonathan Loree, Wilson Miller, Donald Vinh, Nathaniel Bouganim, Gerald Batist, Caroline Letendre, Bertrand Routy. High mortality among hospital-acquired COVID-19 infection in patients with cancer: An observational cohort study from Quebec and British Columbia [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S12-01.
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