Purificación Estévez-García

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.

Atezolizumab Combined With Platinum and Maintenance Niraparib for Recurrent Ovarian Cancer With a Platinum-Free Interval >6 Months: ENGOT-OV41/GEICO 69-O/ANITA Phase III Trial

PURPOSE To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer. METHODS The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270 ) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1. RESULTS Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1–positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs. CONCLUSION Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

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.