دورية أكاديمية
Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial.
| العنوان: | Niraparib, Dostarlimab, and Bevacizumab as Combination Therapy in Pretreated, Advanced Platinum-Resistant Ovarian Cancer: Findings From Cohort A of the OPAL Phase II Trial. |
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| المؤلفون: | Liu JF; Dana-Farber Cancer Institute, Boston, MA., Gaillard S; Johns Hopkins University, Baltimore, MD., Wahner Hendrickson AE; Mayo Clinic, Rochester, MN., Yeku O; Massachusetts General Cancer Center, Boston, MA., Diver E; Stanford Women's Cancer Center, Palo Alto, CA., Gunderson Jackson C; Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK., Arend R; University of Alabama at Birmingham, Birmingham, AL., Ratner E; Yale University, New Haven, CT., Samnotra V; GSK, Waltham, MA., Gupta D; GSK, Waltham, MA., Chung J; GSK, Waltham, MA., Zhang H; GSK, Waltham, MA., Compton N; GSK, Brentford, United Kingdom., Baines A; GSK, Stevenage, United Kingdom., Bacqué E; GSK, Waltham, MA., Liu X; GSK, Waltham, MA., Felicetti B; GSK, Stevenage, United Kingdom., Konecny GE; University of California Los Angeles, Los Angeles, CA. |
| المصدر: | JCO precision oncology [JCO Precis Oncol] 2024 May; Vol. 8, pp. e2300693. |
| نوع المنشور: | Journal Article; Clinical Trial, Phase II; Multicenter Study |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society of Clinical Oncology Country of Publication: United States NLM ID: 101705370 Publication Model: Print Cited Medium: Internet ISSN: 2473-4284 (Electronic) Linking ISSN: 24734284 NLM ISO Abbreviation: JCO Precis Oncol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Alexandria, VA : American Society of Clinical Oncology, [2017]- |
| مواضيع طبية MeSH: | Ovarian Neoplasms*/drug therapy , Bevacizumab*/therapeutic use , Indazoles*/therapeutic use , Piperidines*/therapeutic use , Piperidines*/adverse effects , Drug Resistance, Neoplasm* , Antineoplastic Combined Chemotherapy Protocols*/therapeutic use, Humans ; Female ; Middle Aged ; Aged ; Adult ; Aged, 80 and over ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cohort Studies |
| مستخلص: | Purpose: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). Methods: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. Results: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA -mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA , HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. Conclusion: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA , or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently. |
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| سلسلة جزيئية: | ClinicalTrials.gov NCT03574779 |
| المشرفين على المادة: | 0 (niraparib) 0 (dostarlimab) |
| تواريخ الأحداث: | Date Created: 20240516 Date Completed: 20240516 Latest Revision: 20240905 |
| رمز التحديث: | 20240905 |
| مُعرف محوري في PubMed: | PMC11371093 |
| DOI: | 10.1200/PO.23.00693 |
| PMID: | 38754056 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2473-4284 |
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| DOI: | 10.1200/PO.23.00693 |