The SARS-CoV-2 pandemic significantly affected oncology practice across the globe. There is uncertainty as to the contribution of patients9 demographics and oncologic features to severity and mortality from COVID-19 and little guidance as to the role of anticancer and anti–COVID-19 therapy in this population. In a multicenter study of 890 patients with cancer with confirmed COVID-19, we demonstrated a worsening gradient of mortality from breast cancer to hematologic malignancies and showed that male gender, older age, and number of comorbidities identify a subset of patients with significantly worse mortality rates from COVID-19. Provision of chemotherapy, targeted therapy, or immunotherapy did not worsen mortality. Exposure to antimalarials was associated with improved mortality rates independent of baseline prognostic factors. This study highlights the clinical utility of demographic factors for individualized risk stratification of patients and supports further research into emerging anti–COVID-19 therapeutics in SARS-CoV-2–infected patients with cancer. Significance: In this observational study of 890 patients with cancer diagnosed with SARS-CoV-2, mortality was 33.6% and predicted by male gender, age ≥65, and comorbidity burden. Delivery of cancer therapy was not detrimental to severity or mortality from COVID-19. These patients should be the focus of shielding efforts during the SARS-CoV-2 pandemic. This article is highlighted in the In This Issue feature, p. 1426

Cervical cancer still represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. These figures are unacceptable since cervical cancer, an human papillomavirus-related malignancy, is a largely preventable disease by means of well-established screening and vaccination programs. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches represent a dismal prognosis population. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment landscape of this disease achieving historical overall survival improvements in both the post-platinum and frontline settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to earlier stages of the disease, as the locally advanced setting, whose standard of care has not changed in the last decades with still modest outcomes. As more innovative immunotherapy approaches are in clinical early development in advanced cervical cancer, promising efficacy data are emerging that may shape the future of this disease. This review summarizes the main treatment advances carried out in the field of immunotherapy throughout the past years.

Gastrointestinal stromal tumor (GIST) represents a paradigm for clinically effective targeted inhibition of oncogenic driver mutations in cancer. Five drugs are currently positioned as the standard of care for the treatment of advanced or metastatic GIST patients. This is the result of continuous, deep understanding of KIT and PDGFRA GIST oncogenic drivers as well as the resistance mechanisms associated to tumor progression. However, the complexity of GIST molecular heterogeneity is an evolving field, and critical questions remain open. Specifically, the clinical benefit of approved and/or investigated targeted agents is strikingly modest at advanced stages of the disease when compared with the activity of first-line imatinib. Ripretinib is a novel switch-pocket inhibitor with broad activity against KIT and PDGFRA oncoproteins and has recently demonstrated antitumoral activity across phase I to phase III clinical trials. Therefore, ripretinib has emerged as a new standard of care for advanced, multi-resistant GIST patients. Based on this data, the Food and Drug Administration has granted in 2020 the approval of ripretinib for GIST patients after progression to imatinib, sunitinib and regorafenib. This, in turn, constitutes a major breakthrough in sarcoma drug development, as there have not been new treatment approvals in GIST for nearly a decade. Herein, we provide a critical review on the preclinical and clinical development of ripretinib in GIST. Furthermore, we seek to assess the biological and clinical impact of this new standard of care on the course of the disease, aiming to provide an insight on future treatments strategies for the next coming years.

Background Patients with cancer are particularly susceptible to SARS-CoV-2 infection. The systemic inflammatory response is a pathogenic mechanism shared by cancer progression and COVID-19. We investigated systemic inflammation as a driver of severity and mortality from COVID-19, evaluating the prognostic role of commonly used inflammatory indices in SARS-CoV-2-infected patients with cancer accrued to the OnCovid study. Methods In a multicenter cohort of SARS-CoV-2-infected patients with cancer in Europe, we evaluated dynamic changes in neutrophil:lymphocyte ratio (NLR); platelet:lymphocyte ratio (PLR); Prognostic Nutritional Index (PNI), renamed the OnCovid Inflammatory Score (OIS); modified Glasgow Prognostic Score (mGPS); and Prognostic Index (PI) in relation to oncological and COVID-19 infection features, testing their prognostic potential in independent training (n=529) and validation (n=542) sets. Results We evaluated 1071 eligible patients, of which 625 (58.3%) were men, and 420 were patients with malignancy in advanced stage (39.2%), most commonly genitourinary (n=216, 20.2%). 844 (78.8%) had ≥1 comorbidity and 754 (70.4%) had ≥1 COVID-19 complication. NLR, OIS, and mGPS worsened at COVID-19 diagnosis compared with pre-COVID-19 measurement (p<0.01), recovering in survivors to pre-COVID-19 levels. Patients in poorer risk categories for each index except the PLR exhibited higher mortality rates (p<0.001) and shorter median overall survival in the training and validation sets (p<0.01). Multivariable analyses revealed the OIS to be most independently predictive of survival (validation set HR 2.48, 95% CI 1.47 to 4.20, p=0.001; adjusted concordance index score 0.611). Conclusions Systemic inflammation is a validated prognostic domain in SARS-CoV-2-infected patients with cancer and can be used as a bedside predictor of adverse outcome. Lymphocytopenia and hypoalbuminemia as computed by the OIS are independently predictive of severe COVID-19, supporting their use for risk stratification. Reversal of the COVID-19-induced proinflammatory state is a putative therapeutic strategy in patients with cancer.

Cervical cancer represents a major public health problem, being the fourth most common cancer in incidence and mortality in women worldwide. Patients with recurrent, persistent, or metastatic disease unsuitable for curative therapeutic approaches have a dismal prognosis. Until recently, these patients were only candidates for cisplatin-based chemotherapy plus bevacizumab. However, the introduction of immune checkpoint inhibitors has revolutionized the treatment of this disease, achieving historical overall survival improvements in both the post-platinum and front-line settings. Interestingly, the clinical development of immunotherapy in cervical cancer is currently advancing to the locally advanced setting, although preliminary efficacy outcomes in this setting have been disappointing so far. Moreover, promising data are emerging from early-phase trials on novel immunotherapy approaches, such as human papillomavirus therapeutic vaccines and adoptive cell therapy. This review summarizes the main clinical trials carried out in the field of immunotherapy in the last several years.