Cristina Churruca

An ambispective, real-world multi-center study of DOstarlimab in patients with Recurrent or Advanced DNA mismatch repair deficient/microsatellite instability-high endometrial cancer (GEICO 120-R/DORA study)

Patients with advanced or recurrent endometrial cancer who experience progression following platinum-based chemotherapy have limited treatment options. The phase I GARNET trial showed the high efficacy of dostarlimab in treating mismatch repair deficient (dMMR) and/or microsatellite instability-high (MSI-H) endometrial cancer. DORA is a multi-center, ambispective, observational real-world study evaluating the efficacy and safety of dostarlimab. The study included patients with dMMR/MSI-H endometrial cancer who had experienced tumor progression on or after a platinum-based treatment and had received at least 1 cycle of dostarlimab within the Spanish Expanded Access Program. The primary endpoints were objective response rate and duration of response. A total of 129 patients from 57 of the Spanish Research Group for Gynaecological Cancer (GEICO) affiliated hospitals were enrolled, with 125 evaluable for radiological response. The median duration of dostarlimab administration was 8.8 months (interquartile range; 13.2), and 73 patients (57%) remained on therapy at the data cutoff. With a median follow-up of 11.6 months (range; 0.8-30.1), the objective response rate was 53.6% (95% CI 44.4 to 62.5). Complete response was observed in 27 patients (21.6%), and partial response in 40 (32%), with a median time to response of 2.9 months (95% CI 2.6 to 3.6). The median duration of response was not reached. The probability of maintaining the response at 12 and 24 months was 84.98% (95% CI 70.8 to 92.5) and 73.39% (95% CI 50.5 to 86.9), respectively. Treatment was discontinued due to toxicity in 4.7% of patients. Dostarlimab monotherapy in dMMR/MSI-H endometrial cancer patients shows similar efficacy in real-world practice to that observed in the GARNET trial.

Molecular Results and Potential Biomarkers Identified from the Phase 3 MILO/ENGOT-ov11 Study of Binimetinib versus Physician Choice of Chemotherapy in Recurrent Low-Grade Serous Ovarian Cancer

Abstract Purpose: We present the results of a post hoc tumor tissue analysis from the phase 3 MILO/ENGOT-ov11 study (NCT01849874). Patients and Methods: Mutation/copy-number analysis was performed on tissue obtained pre-randomization. The Kaplan–Meier method was used to estimate progression-free survival (PFS). Unbiased univariate analysis, Cox regression, and binary logistic regression were used to test associations between mutation status and outcomes, including PFS and binary response by local RECIST 1.1. Results: MILO/ENGOT-ov11 enrolled 341 patients, ranging in age from 22 to 79, from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or physician's choice of chemotherapy (PCC). The most commonly altered gene was KRAS (33%). In 135 patients treated with binimetinib with response rate (RR) data, other detected MAPK pathway alterations included: NRAS (n = 11, 8.1%), BRAF V600E (n = 8, 5.9%), RAF1 (n = 2, 1.5%), and NF1 (n = 7, 5.2%). In those with and without MAPK pathway alterations, the RRs with binimetinib were 41% and 13%, respectively. PFS was significantly longer in patients with, compared with those without, MAPK pathway alterations treated with binimetinib [HR, 0.5; 95% confidence interval (CI) 0.31–0.79]. There was a nonsignificant trend toward PFS improvement in PCC-treated patients with MAPK pathway alterations compared with those without (HR, 0.82; 95% CI, 0.43–1.59). Conclusions: Although this hypothesis-generating analysis is limited by multiple testing, higher RRs and longer PFS were seen in patients with low-grade serous ovarian cancer (LGSOC) treated with binimetinib, and to a lesser extent in those treated with PCC, who harbored MAPK pathway alterations. Somatic tumor testing should be routinely considered in patients with LGSOC and used as a future stratification factor.

Clinical outcomes and subsequent therapy in patients with platinum-sensitive recurrent ovarian cancer deriving long-term benefit from maintenance niraparib: a subgroup analysis of the GEICO-88R study.

To describe characteristics, clinical outcomes, and subsequent therapies in patients receiving long-term maintenance niraparib in the Spanish expanded-access program. This retrospective observational study (NCT04546373) described patient characteristics, treatment exposure, and clinical outcomes in patients receiving maintenance niraparib for high-grade serous platinum-sensitive recurrent ovarian cancer. Subgroup analyses in patients receiving niraparib for ≥1 year ("long-term responders") were prespecified; additional post hoc analyses explored outcomes in patients treated for ≥2 years ("sustained long-term responders"). In this real-world population of 316 patients (predominantly BRCA wildtype), 107 (34%) were long-term responders and 61 (19%) were sustained long-term responders. Compared with patients discontinuing niraparib within 1 year, the long-term responders subgroup included a higher proportion with primary debulking surgery and no residual disease after cytoreductive surgery and a lower proportion with >4 prior lines of systemic therapy, International Federation of Gynecology and Obstetrics stage IV disease, measurable disease at niraparib initiation, and Eastern Cooperative Oncology Group performance status 1. Tolerability was similar regardless of treatment duration. After discontinuing niraparib, the most frequently administered regimens were platinum-based. Response rates to the first post-niraparib line were 37% to 44%, and median progression-free survival was 7.0 months in non-long-term responders and 7.9 months in long-term responders. Median overall survival was 56.9 months in long-term responders (49.1 months' median follow-up) and was not reached in the sustained long-term responders subgroup. Mature results from the GEICO-88R study continue to support the effectiveness and tolerability of maintenance niraparib in platinum-sensitive recurrent ovarian cancer. A subset of patients experienced long-term disease control. The efficacy of subsequent treatment appeared similar irrespective of niraparib duration.

Addressing unmet needs in long-term survivors of ovarian cancer (ENGOT ov40/NOGGO S13/GEICO 71-R/Expression VI): insights from a Spanish cohort

Ovarian cancer remains a significant global health concern. Contemporary therapeutics have led to an increased number of long-term survivors. This research investigates the unmet needs of long-term ovarian cancer survivors in Spain, focusing on persistent side effects, patient concerns, lifestyle changes, and ongoing challenges. This is a multi-center, cross-sectional, observational study, assessing the results from the international North-Eastern German Society of Gynecological Oncology survey, Expression VI - Long-term survival with ovarian cancer in Spain. Participants were identified during follow-up visits at oncology departments. A structured questionnaire of 68 items, including demographic, clinical, psychosocial, and lifestyle domains, was completed anonymously in printed format, with implied consent through survey completion. A total of 250 long-term ovarian cancer survivors from Spain, defined as patients diagnosed of malignant ovarian cancer with a survival ≥8 years since diagnosis (median age at diagnosis 52 years; median survival time 11 years), completed the survey. A substantial number of participants continued to experience long-term side effects, including gastrointestinal (90%), dermatologic (91.6%), and neurologic symptoms, such as memory problems (15.1%) and concentration difficulties (10.8%). Nearly half of the survivors (47.3%) expressed concerns about nervousness, 43.6% reported ongoing pain, and 40% struggled with sleep disturbances. Lifestyle changes after cancer diagnostic were significant, with 56.5% of smoker participants quitting or reducing smoking and 41.6% adopting healthier diets. Finally, our results indicate that most participants received some form of follow-up, primarily through blood biomarker monitoring (87.0%) and imaging tests (73.0%). This study highlights the persistent challenges among long-term ovarian cancer survivors in Spain, stressing the need for more comprehensive, tailored aftercare. These findings may be generalized to other regions, emphasizing the importance of addressing ongoing side effects and unmet care needs to improve survivors' long-term quality of life. Enhanced follow-up care, patient support, and effective communication are essential components of this effort.

A Study of MEK162 vs. Physician's Choice Chemotherapy in Patients With Low-grade Serous Ovarian, Fallopian Tube or Peritoneal Cancer

The MILO Study (MEK Inhibitor in Low-grade Serous Ovarian Cancer) is a Phase 3 study during which patients with recurrent or persistent low-grade serous (LGS) carcinomas of the ovary, fallopian tube or primary peritoneum will receive either investigational study drug MEK162 or a chemotherapy chosen by the physician (liposomal doxorubicin, paclitaxel or topotecan). Patients will be followed to compare the effectiveness of the study drug to that of the selected chemotherapies. Patients may be eligible to crossover from physician's choice chemotherapy to MEK162 if they meet certain inclusion criteria including centrally confirmed disease progression. Approximately 360 patients from North America, Europe and Australia will be enrolled in this study.