
PURPOSE Despite therapeutic advances, outcomes for patients with platinum-resistant/refractory ovarian cancer remain poor. Selective glucocorticoid receptor modulation with relacorilant may restore chemosensitivity and enhance chemotherapy efficacy. METHODS This three-arm, randomized, controlled, open-label phase II study (ClinicalTrials.gov identifier: NCT03776812 ) enrolled women with recurrent, platinum-resistant/refractory, high-grade serous or endometrioid epithelial ovarian, primary peritoneal, or fallopian tube cancer, or ovarian carcinosarcoma treated with ≤4 prior chemotherapeutic regimens. Patients were randomly assigned 1:1:1 to (1) nab-paclitaxel (80 mg/m2) + intermittent relacorilant (150 mg the day before, of, and after nab-paclitaxel); (2) nab-paclitaxel (80 mg/m2) + continuous relacorilant (100 mg once daily); or (3) nab-paclitaxel monotherapy (100 mg/m2). Nab-paclitaxel was administered on days 1, 8, and 15 of each 28-day cycle. The primary end point was progression-free survival (PFS) by investigator assessment; objective response rate (ORR), duration of response (DOR), overall survival (OS), and safety were secondary end points. RESULTS A total of 178 women were randomly assigned. Intermittent relacorilant + nab-paclitaxel improved PFS (hazard ratio [HR], 0.66; log-rank test P = .038; median follow-up, 11.1 months) and DOR (HR, 0.36; P = .006) versus nab-paclitaxel monotherapy, while ORR was similar across arms. At the preplanned OS analysis (median follow-up, 22.5 months), the OS HR was 0.67 ( P = .066) for the intermittent arm versus nab-paclitaxel monotherapy. Continuous relacorilant + nab-paclitaxel showed numerically improved median PFS but did not result in significant improvement over nab-paclitaxel monotherapy. Adverse events were comparable across study arms, with neutropenia, anemia, peripheral neuropathy, and fatigue/asthenia being the most common grade ≥3 adverse events. CONCLUSION Intermittent relacorilant + nab-paclitaxel improved PFS, DOR, and OS compared with nab-paclitaxel monotherapy. On the basis of protocol-prespecified Hochberg step-up multiplicity adjustment, the primary end point did not reach statistical significance ( P < .025). A phase III evaluation of this regimen is underway (ClinicalTrials.gov identifier: NCT05257408 ).
Paclitaxel, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Ovarian Epithelial, Quimioteràpia combinada, 3211 Oncology and carcinogenesis, Albumins, Antineoplastic Combined Chemotherapy Protocols, Humans, 1112 Oncology and Carcinogenesis, FUNCTION ITEM BANK, Oncology & Carcinogenesis, Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ovarian Epithelial; Chronic Disease; Female; Humans; Ovarian Neoplasms; Paclitaxel, Platí, Ovarian Neoplasms, Science & Technology, Other subheadings::Other subheadings::Other subheadings::/drug therapy, 1103 Clinical Sciences, ORIGINAL REPORTS, Ovaris - Càncer - Tractament, Oncology, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas, Chronic Disease, Female, DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms, Life Sciences & Biomedicine, TAXANE, GLUCOCORTICOID-RECEPTOR EXPRESSION
Paclitaxel, TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada, Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia, ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Ovarian Epithelial, Quimioteràpia combinada, 3211 Oncology and carcinogenesis, Albumins, Antineoplastic Combined Chemotherapy Protocols, Humans, 1112 Oncology and Carcinogenesis, FUNCTION ITEM BANK, Oncology & Carcinogenesis, Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Ovarian Epithelial; Chronic Disease; Female; Humans; Ovarian Neoplasms; Paclitaxel, Platí, Ovarian Neoplasms, Science & Technology, Other subheadings::Other subheadings::Other subheadings::/drug therapy, 1103 Clinical Sciences, ORIGINAL REPORTS, Ovaris - Càncer - Tractament, Oncology, ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias de las glándulas endocrinas::neoplasias ováricas, Chronic Disease, Female, DISEASES::Neoplasms::Neoplasms by Site::Endocrine Gland Neoplasms::Ovarian Neoplasms, Life Sciences & Biomedicine, TAXANE, GLUCOCORTICOID-RECEPTOR EXPRESSION
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