Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial

Purpose: Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers. Patients and methods: Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus-negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points. Results: Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life. Conclusion: The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population

Métodos de superação de dormência em sementes de flamboyant.

The flamboyant tree (Delonix regia) is known for its exuberant flowering. It shows great variation in seeds viability, depending on the cutaneous water proofing, requiring processes to break dormancy. The objective of this study was to evaluate methods of breaking the physical barrier of seeds. In the greenhouse, seeds were subjected to different treatments to overcome the cutaneous restriction: mechanical scarification on the ventral part; thermal shock with soaking seeds in water at 80 °C for 10 min; soaking the seeds in sulfuric acid, and control, without intervention. It was observed that the mechanical scarification provided the best results for dormancy breaking of the seeds.O flamboyant (Delonix regia) é reconhecido por sua exuberância na floração. Apresenta sementes com grande variação na viabilidade, em função da impermeabilidade tegumentar, necessitando de processos para superação da dormência. Neste sentido, objetivou-se com este trabalho, avaliar métodos para quebra da dormência das sementes em casa de vegetação. As sementes foram submetidas a diferentes tratamentos para superar a restrição tegumentar: escarificação mecânica na parte ventral; choque térmico com imersão das sementes em água a 80 ºC por 10 min e imersão das sementes em ácido sulfúrico, tendo como controle a semeadura sem intervenção. Observou-se que a escarificação mecânica proporcionou os melhores resultados para quebra de dormência das sementes