Background Cancer patients are thought to have an increased risk of developing severe Coronavirus Disease 2019 (COVID-19) infection and of dying from the disease. In this work, predictive factors for COVID-19 severity and mortality in cancer patients were investigated. Patients and Methods In this large nationwide retro-prospective cohort study, we collected data on patients with solid tumours and COVID-19 diagnosed between March 1 and June 11, 2020. The primary endpoint was all-cause mortality and COVID-19 severity, defined as admission to an intensive care unit (ICU) and/or mechanical ventilation and/or death, was one of the secondary endpoints. Results From April 4 to June 11, 2020, 1289 patients were analysed. The most frequent cancers were digestive and thoracic. Altogether, 424 (33%) patients had a severe form of COVID-19 and 370 (29%) patients died. In multivariate analysis, independent factors associated with death were male sex (odds ratio 1.73, 95%CI: 1.18-2.52), ECOG PS ≥ 2 (OR 3.23, 95%CI: 2.27-4.61), updated Charlson comorbidity index (OR 1.08, 95%CI: 1.01-1.16) and admission to ICU (OR 3.62, 95%CI 2.14-6.11). The same factors, age along with corticosteroids before COVID-19 diagnosis, and thoracic primary tumour site were independently associated with COVID-19 severity. None of the anticancer treatments administered within the previous 3 months had any effect on mortality or COVID-19 severity, except cytotoxic chemotherapy in the subgroup of patients with detectable SARS-CoV-2 by RT-PCR, which was associated with a slight increase of the risk of death (OR 1.53; 95%CI: 1.00-2.34; p = 0.05). A total of 431 (39%) patients had their systemic anticancer treatment interrupted or stopped following diagnosis of COVID-19. Conclusions Mortality and COVID-19 severity in cancer patients are high and are associated with general characteristics of patients. We found no deleterious effects of recent anticancer treatments, except for cytotoxic chemotherapy in the RT-PCR-confirmed subgroup of patients. In almost 40% of patients, the systemic anticancer therapy was interrupted or stopped after COVID-19 diagnosis.

Immune checkpoint inhibitors represent a major therapeutic advance in non-small-cell lung cancer with several approved anti-programmed death-1 and anti-programmed death-L1 immunotherapies. A majority of patients however, will not respond to immune checkpoint inhibitors and display primary resistance while a subset of initially responsive patients will present secondary resistance. Thus, there is a crucial need for biomarkers to enable better prediction and diagnosis, and to overcome such resistance. Along with improvement in the understanding of immune escape, new biomarkers are being developed, including large scale proteomic, genomic and transcriptomic approaches in tumor and blood samples. We review the novel biomarkers that have been investigated in non-small-cell lung cancer and discuss how they can rationalize therapeutic strategies.

Aims: Anti-PD-1/PD-L1 can face the issue of tumor resistance in advanced non-small cell lung cancer (aNSCLC), mostly as primary resistance to the treatment. Still, disease progression (PD) also occurs after prior durable clinical benefit (DCB). Comparison of both situations and tools to evaluate residual benefit of PD-1/PD-L1 blockade are needed to understand and manage resistance. Methods: We reviewed aNSCLCs with anti-PD-1/PD-L1 monotherapy, and disease progression per RECIST 1.1 (PD) in our center. Primary objective was comparison of post-progression survival (PPS) in primary resistance versus PD after DCB. Secondary objectives were to characterize patterns of PD after DCB; assess the feasibility and relevance of Tumor Growth Rate (TGR) in PD after DCB. Results: 148 patients were included. Median PPS were 5.2months (95% CI: 2.6-6.5) and 21.3months (95% CI: 18.5-36.3) (p<0.0001) for primary resistance and PD after DCB respectively. Multivariable hazard ratio for death in PD after DCB versus primary resistance was 0.14 (95% CI: 0.07-0.30). 76.7% of PD after DCB occurred in ≤3 lesions; 72.1% occurred only in preexisting lesions. TGR suggested a persistent benefit of PD-1/PD-L1 blockade in at least 44.2% of cases. Conclusions: PD after DCB was an independent factor of longer post-progression survival, with specific patterns of progression. TGR is a promising tool to assess residual benefit of immunotherapy.