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Article . 2023
License: CC BY NC ND
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Journal of Clinical Oncology
Article . 2023 . Peer-reviewed
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Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study

Authors: Nicoletta Colombo; Toon Van Gorp; Ursula A. Matulonis; Ana Oaknin; Rachel N. Grisham; Gini F. Fleming; Alexander B. Olawaiye; +6 Authors

Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study

Abstract

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 ).

Keywords

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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    popularity
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    influence
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
10
Top 10%
Average
Top 10%
Green
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