Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

\ua92019 American Association for Cancer Research.PURPOSE: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623). PATIENTS AND METHODS: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity. RESULTS: Of the 55 patients, 51% had received ≥2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab + doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0+-9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0+-9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed. CONCLUSIONS: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer

PURPOSE: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623). PATIENTS AND METHODS: Patients with recurrent or metastatic cervical cancer received tisotumab vedotin 2.0 mg/kg every 3 weeks until progressive disease, unacceptable toxicity, or consent withdrawal. The primary objective was safety and tolerability. Secondary objectives included antitumor activity. RESULTS: Of the 55 patients, 51% had received ≥2 prior lines of treatment in the recurrent or metastatic setting; 67% had prior bevacizumab + doublet chemotherapy. Fifty-one percent of patients had squamous cell carcinoma. The most common grade 3/4 treatment-emergent adverse events (AEs) were anemia (11%), fatigue (9%), and vomiting (7%). No grade 5 treatment-related AEs occurred. Investigator-assessed confirmed objective response rate (ORR) was 24% [95% confidence interval (CI): 13%-37%]. Median duration of response (DOR) was 4.2 months (range: 1.0+ -9.7); four patients responded for >8 months. The 6-month progression-free survival (PFS) rate was 29% (95% CI: 17%-43%). Independent review outcomes were comparable, with confirmed ORR of 22% (95% CI: 12%-35%), median DOR of 6.0 months (range: 1.0+ -9.7), and 6-month PFS rate of 40% (95% CI: 24%-55%). Tissue factor expression was confirmed in most patients; no significant association with response was observed. CONCLUSIONS: Tisotumab vedotin demonstrated a manageable safety profile and encouraging antitumor activity in patients with previously treated recurrent or metastatic cervical cancer

Injury and Poisoning Profile in Anabolic Steroid Users

Study objective: This study investigated the 1-year risk of injuries and poisonings among anabolic androgenic steroid users compared with controls from the general population. Methods: In a cohort study conducted in Denmark, 1,189 anabolic androgenic steroid users were identified through a national antidoping program and matched with 59,450 controls. Participants were followed for 1 year. Data on hospital contacts, educational length, and occupational status were retrieved from nationwide registries. The primary outcomes were the incidence of injuries and poisonings. The secondary outcomes differentiated between fracture and nonfracture injuries, and medicinal versus nonmedicinal causes of poisonings, and described specific causes of injury-related hospital contacts. Results: Anabolic androgenic steroid users had significantly higher incidences of injuries and poisonings compared with controls. The risk difference for any injury was 7.8% (95% confidence interval [CI] 5.5 to 10.2) and the adjusted hazard ratio (aHR) was 1.46 (95% CI 1.29 to 1.66). Specifically, the risk of fractures was more than doubled among anabolic androgenic steroid users (aHR of 2.23, 95% CI 1.72 to 2.89), with head injuries being particularly prevalent. The risk difference for any poisoning was 1.2% (95% CI 0.5 to 1.9) and the aHR was 2.98 (95% CI 1.82 to 4.90). Medicinal poisoning was the most common poisoning among anabolic androgenic steroid users, with an aHR of 3.53 (95% CI 1.94 to 6.41). Conclusion: Anabolic androgenic steroid use is associated with an increased risk of both injuries and poisonings, thereby quantifying a substantial risk of external harm among users.</p