Better late than never: Brachytherapy is more important than timing in treatment of locally advanced cervical cancer.

PURPOSE: To evaluate the utilization of brachytherapy and duration of treatment on overall survival for locally advanced cervical cancer. METHODS: The National Cancer Database (NCDB) was queried to identify stage II-IVA cervical cancer patients diagnosed in the United States between 2004 and 2015 who were treated with definitive chemoradiation therapy. We defined standard of care (SOC) treatment as receiving external beam radiation therapy (EBRT) and concurrent chemotherapy, brachytherapy (BT), and completing treatment within 8 weeks, and compared SOC treatment to non-SOC. The primary outcome was overall survival (OS). We also evaluated the effect of sociodemographic and clinical variables on receiving SOC. RESULTS: We identified 10,172 women with locally advanced cervical cancer primarily treated with chemotherapy and concurrent EBRT of which 6047 (59.4%) patients received brachytherapy, and only 2978 (29.3%) completed treatment within 8 weeks (SOC). Receipt of SOC was associated with significantly improved overall survival (median OS 131.0 mos vs 95.5 mos, 78.1 mos, 49.2 mos; p < 0.0001). Furthemore, in patients whose treatment extended beyond 8 weeks, brachytherapy was still associated with an improved survival (median OS 95.5 vs 49.2 mos, p < 0.0001). More advanced stage, Non-Hispanic Black race, lower income, lack of insurance or government insurance, less education, and rural residence were associated with decreased likelihood of receiving SOC. CONCLUSIONS: Completing standard of care concurrent chemoradiation therapy and brachytherapy in the recommended 8 weeks was associated with a superior overall survival. Patients who received brachytherapy boost show superior survival to patients receiving EBRT alone, regardless of treatment duration. Disparities in care for vulnerable populations highlight the challenges and importance of care coordination for patients with cervical cancer.

A T-cell engaging bispecific antibody with a tumor-selective bivalent folate receptor alpha binding arm for the treatment of ovarian cancer.

The use of T-cell engagers (TCEs) to treat solid tumors is challenging, and several have been limited by narrow therapeutic windows due to substantial on-target, off-tumor toxicities due to the expression of low levels of target antigens on healthy tissues. Here, we describe TNB-928B, a fully human TCE that has a bivalent binding arm for folate receptor alpha (FRα) to selectively target FRα overexpressing tumor cells while avoiding the lysis of cells with low levels of FRα expression. The bivalent design of the FRα binding arm confers tumor selectivity due to low-affinity but high-avidity binding to high FRα antigen density cells. TNB-928B induces preferential effector T-cell activation, proliferation, and selective cytotoxic activity on high FRα expressing cells while sparing low FRα expressing cells. In addition, TNB-928B induces minimal cytokine release compared to a positive control TCE containing OKT3. Moreover, TNB-928B exhibits substantial ex vivo tumor cell lysis using endogenous T-cells and robust tumor clearance in vivo, promoting T-cell infiltration and antitumor activity in mouse models of ovarian cancer. TNB-928B exhibits pharmacokinetics similar to conventional antibodies, which are projected to enable favorable administration in humans. TNB-928B is a novel TCE with enhanced safety and specificity for the treatment of ovarian cancer.