Purpose: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2+ locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies.Patients and Methods: This was a phase II, open-label, multicenter, single-arm study of patients with HER2+ (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety.Results: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%–66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6–8.9) and 13.9 months (95% CI, 9.1–NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred.Conclusions: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2+ locally advanced or mUC who had failed at least one line of systemic chemotherapy.

PURPOSE: To evaluate the efficacy and safety of disitamab vedotin (DV, RC48-ADC), a novel humanized anti–human epidermal growth factor receptor 2 (HER2) antibody conjugated with monomethyl auristatin E, in patients with HER2-positive locally advanced or metastatic urothelial carcinoma (UC) refractory to standard or regular therapies. PATIENTS AND METHODS: The data analyzed and reported are from two phase II, open-label, multicenter, single-arm studies (RC48-C005 and RC48-C009) in patients with HER2-positive (immunohistochemistry 3+ or 2+) locally advanced or metastatic UC who have progressed on at least one previous line of systemic chemotherapy. Patients received DV treatment (2 mg/kg IV infusion, once every 2 weeks). The primary end point was objective response rate (ORR) assessed by a blinded independent review committee (BIRC). Progression-free survival (PFS), overall survival (OS), and safety were also assessed. RESULTS: One hundred and seven patients were enrolled in total. The overall confirmed ORR by BIRC was 50.5% (95% CI, 40.6 to 60.3). Consistent results were observed in prespecified subgroups including patients with liver metastasis and patients previously treated with anti–PD-1/L1 therapies. By the cutoff date of May 10, 2022, the median duration of response was 7.3 months (95% CI, 5.7 to 10.8). The median PFS and OS were 5.9 months (95% CI, 4.3 to 7.2) and 14.2 months (95% CI, 9.7 to 18.8), respectively. The most common treatment-related adverse events (TRAEs) were peripheral sensory neuropathy (68.2%), leukopenia (50.5%), AST increased (42.1%), and neutropenia (42.1%). Fifty-eight (54.2%) patients experienced grade ≥3 TRAEs, including peripheral sensory neuropathy (18.7%) and neutropenia (12.1%). CONCLUSION: DV demonstrated a promising efficacy with a manageable safety profile in patients with HER2-positive locally advanced or metastatic UC who had progressed on at least one line of systemic chemotherapy.

BACKGROUND: It has been reported that antidiabetic drugs affect the risk of cancer and the prognosis of patients with diabetes, but few studies have demonstrated the influence of different antidiabetic agents on outcomes after anticancer therapy among patients with cancer. The objective of this study was to evaluate the influence of the antidiabetic drugs metformin and insulin on the prognosis of patients with advanced nonsmall cell lung cancer (NSCLC) plus type 2 diabetes who received first‐line chemotherapy.METHODS: Data on patients with NSCLC who had diabetes from 5 hospitals in China during January 2004 to March 2009 were reviewed retrospectively. Ninety‐nine patients were included in the final analysis. The influence of metformin and insulin on chemotherapy response rates and survival in these patients was evaluated.RESULTS: Chemotherapy with metformin (Group A) produced superior results compared with insulin (Group B) and compared with drugs other than metformin and insulin (Group C) in terms of both progression‐free survival (PFS) (8.4 months vs 4.7 months vs 6.4 months, respectively; P = .002) and overall survival (OS) (20.0 months vs 13.1 months vs 13.0 months, respectively; P = .007). Although no significant differences in the response rate (RR) were observed between these 3 groups, when groups B and C (ie, the nonmetformin group) were combined, there was a tendency for better disease control in Group A than that in nonmetformin group. No significant difference in survival was observed between chemotherapy with insulin (Group B) versus other drugs (Group C).CONCLUSIONS: The current data suggested that metformin may improve chemotherapy outcomes and survival for patients who have NSCLC with diabetes. Cancer 2011;. © 2011 American Cancer Society.

Immune checkpoint inhibitors (ICIs), as one of the innovative types of immunotherapies, including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors, have obtained unprecedented benefit in multiple malignancies. However, the immune response activation in the body organs could arise immune-related adverse events (irAEs). Checkpoint inhibitor colitis (CIC) is the most widely reported irAEs. However, some obscure problems, such as the mechanism concerning gut microbiota, the confusing differential diagnosis with inflammatory bowel disease (IBD), the optimal steroid schedule, the reintroduction of ICIs, and the controversial prognosis features, influence the deep understanding and precise diagnosis and management of CIC. Herein, we based on these problems and comprehensively summarized the relevant studies of CIC in patients with NSCLC, further discussing the future research direction of this specific pattern of irAEs.

Owing to the limitations of the present efforts on drug discovery against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the lack of the understanding of the biological regulation mechanisms underlying COVID-19, alternative or novel therapeutic targets for COVID-19 treatment are still urgently required. SARS-CoV-2 infection and immunity dysfunction are the two main courses driving the pathogenesis of COVID-19. Both the virus and host factors are potential targets for antiviral therapy. Hence, in this study, the current therapeutic strategies of COVID-19 have been classified into “target virus” and “target host” categories. Repurposing drugs, emerging approaches, and promising potential targets are the implementations of the above two strategies. First, a comprehensive review of the highly acclaimed old drugs was performed according to evidence-based medicine to provide recommendations for clinicians. Additionally, their unavailability in the fight against COVID-19 was analyzed. Next, a profound analysis of the emerging approaches was conducted, particularly all licensed vaccines and monoclonal antibodies (mAbs) enrolled in clinical trials against primary SARS-CoV-2 and mutant strains. Furthermore, the pros and cons of the present licensed vaccines were compared from different perspectives. Finally, the most promising potential targets were reviewed, and the update of the progress of treatments has been summarized based on these reviews.

Immune checkpoint inhibitors (ICIs) that target cytotoxic T lymphocyte antigen 4, programmed cell death-1, and PD-ligand 1 have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. ICIs are increasingly being used in early cancer settings and in combination with various other types of therapies, including targeted therapy, radiotherapy, and chemotherapy. However, despite the excellent therapeutic effect of ICIs, these medications typically result in a broad spectrum of toxicity reactions, termed immune-related adverse events (irAEs). Of all irAEs, cardiotoxicity, uncommon but with high mortality, has not been well recognized. Herein, based on previous published reports and current evidence, we summarize the incidence, diagnosis, clinical manifestations, underlying mechanisms, treatments, and outcomes of ICI-associated cardiotoxicity and discuss possible management strategies. A better understanding of these characteristics is critical to managing patients with ICI-associated cardiotoxicity.