RESUMEN
Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).
Ongoing Phase II study randomizing vaccine OSE2101 +/- Pembrolizumab vs supportive care as maintenance in platinum-sensitive recurrent ovarian cancer.
RESUMEN
At first recurrence, platinum-sensitive ovarian cancer (PSOC) is frequently treated with platinum-based chemotherapy doublets plus bevacizumab, then single-agent bevacizumab. Most patients' disease progresses within a year after chemotherapy, emphasizing the need for novel strategies. Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate, comprises a folate receptor alpha (FRα)-binding antibody and tubulin-targeting payload (maytansinoid DM4). In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.
Most patients with ovarian cancer are initially treated with platinum-based chemotherapy. If the cancer reappears/recurs after more than 6 months following this therapy, it is called platinum-sensitive ovarian cancer (PSOC). Patients with PSOC usually receive additional platinum-based chemotherapy along with bevacizumab, a drug that reduces tumor growth by decreasing its blood supply. If patients improve or are stable on this therapy, they are usually kept on bevacizumab alone for 'maintenance therapy'. Unfortunately, this maintenance therapy does not work long-term in all patients, so better long-term treatments are needed. The GLORIOSA (NCT05445778) clinical trial will compare maintenance therapy with bevacizumab alone to maintenance therapy with bevacizumab plus a drug called mirvetuximab soravtansine-gynx (MIRV) to determine which therapy leads to better results in patients with PSOC. MIRV is made up of an antibody that binds to a specific protein (folate receptor alpha [FRα]) on cancer cells to directly deliver a cancer-killing drug. MIRV received US FDA approval to be used as a therapy for patients with ovarian cancer who are resistant to platinum-based chemotherapy and express high levels of FRα. The GLORIOSA trial will study maintenance therapy with MIRV plus bevacizumab in patients with PSOC who have not had cancer progression after second-line platinum-based chemotherapy plus bevacizumab, and whose cancer expresses high amounts of FRα. The main purpose of this trial is to determine if MIRV plus bevacizumab leads to better patient survival and decreases cancer growth and spread when compared with bevacizumab alone.
RESUMEN
Epithelial ovarian cancer (EOC) remains a highly-lethal gynecological malignancy, characterized by frequent recurrence, chemotherapy resistance and poor 5-year survival. Identifying novel predictive molecular markers remains an overdue challenge in the disease's clinical management. Herein, in silico analysis of TCGA-OV highlighted the tRNA-derived internal fragment (i-tRF-GlyGCC) among the most abundant tRFs in ovarian tumors, while target prediction and gene ontology (GO) enrichment analysis predicted its implication in key biological processes. Thereafter, i-tRF-GlyGCC levels were quantified in a screening EOC (n = 98) and an institutionally-independent serous ovarian cancer (SOC) validation cohort (n = 100, OVCAD multicenter study). Disease progression and patient death were used as clinical endpoints for the survival analysis. Internal validation was performed by bootstrap analysis and the clinical net benefit was estimated by decision curve analysis. The analysis highlighted the significant association of i-tRF-GlyGCC with advanced FIGO stages, suboptimal debulking and most importantly, with early progression and poor overall survival of EOC patients. The OVCAD validation cohort corroborated the unfavorable predictive value of i-tRF-GlyGCC in EOC. Ultimately, evaluation of i-tRF-GlyGCC with the established/clinically used prognostic markers offered superior patient risk-stratification and enhanced clinical benefit in EOC prognosis. In conclusion, i-tRF-GlyGCC assessment could aid towards personalized prognosis and support precision medicine decisions in EOC.
RESUMEN
OBJECTIVE: To evaluate lymphangiogenesis and lymph vessel space involvement in different subsets of endometrial cancer using podoplanin, a specific marker for lymphatic endothelium. METHODS: Sixty-two patients undergoing a hysterectomy with lymphadenectomy were included. Distribution of histopathologic subtypes was as follows: 30 endometrioid (48%), 18 serous (29%), 9 clear cell carcinoma (15%), and 5 carcinosarcomas (8%). Distribution of surgical stage according to the International Federation of Gynecology and Obstetrics 2009 criteria was as follows: 33 stage I (53%), 7 stage II (11%), 1 stage IIIA (2%), 15 stage IIIC1 (24%), and 6 stage IIIC2 (10%). Tumor samples were immunostained for podoplanin and the panendothelial marker, CD31. Peritumoral and intratumoral blood vessel density and lymph vessel density were assessed using an image analysis system that calculated mean vessel cross-sectional area (in micrometer squared) and vessel density (per millimeter squared). Presence of blood vessel space involvement and lymph vessel space involvement was screened for. The findings were linked with clinical outcome using Cox regression. RESULTS: Twenty-one patients (34%) experienced recurrence, and 13 (21%) died of disease. Univariate analysis showed that blood vessel space involvement was related to worse overall survival (hazard ratio, 6.59; 95% confidence interval, 1.30-120). Multivariate analyses confirmed the prognostic importance of this variable for overall survival (hazard ratio, 7.52; 95% confidence interval, 1.32-144). CONCLUSION: Blood vessel space involvement is a prognostic marker for worse survival. Although lymph vessels were stained with the most reliable marker, podoplanin, lymph vessel density and lymphovascular space involvement do not seem to be of prognostic importance.