Predictors of long-term progression-free survival (PFS) in niraparib-treated patients (pts) from the PRIMA/ENGOT-OV26/GOG-3012 study.

person Whitney Graybill Medical University of South Carolina, Charleston, SC info_outline Whitney Graybill, Beatriz Pardo, David M. O'Malley, Ignace Vergote, Bradley J. Monk, Annika Auranen, Larry J. Copeland, Roberto Sabbitini, Thomas J Herzog, Philippe Follana, Bhavana Pothuri, Elena Ioana Braicu, Colleen McCormick, Alfonso Yubero-Esteban, Richard G. Moore, Peter Vuylsteke, Nicoline Raashouu-Jensen, Whitney York, John Hartman, Antonio Gonzalez Martin

Authors person Whitney Graybill Medical University of South Carolina, Charleston, SC info_outline Whitney Graybill, Beatriz Pardo, David M. O'Malley, Ignace Vergote, Bradley J. Monk, Annika Auranen, Larry J. Copeland, Roberto Sabbitini, Thomas J Herzog, Philippe Follana, Bhavana Pothuri, Elena Ioana Braicu, Colleen McCormick, Alfonso Yubero-Esteban, Richard G. Moore, Peter Vuylsteke, Nicoline Raashouu-Jensen, Whitney York, John Hartman, Antonio Gonzalez Martin Organizations Medical University of South Carolina, Charleston, SC, Institut Català d’Oncologia L’Hospitalet de Llobregat, Hospital Duran i Reynals, IDIBELL, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Barcelona, Spain, Division of Gynecologic Oncology, Ohio State University, James Comprehensive Cancer Center, Columbus, OH, Gynecological Oncology, University Hospitals Leuven, Leuven, Belgium, Division of Gynecological Oncology, HonorHealth Research Institute, University of Arizona College of Medicine, Phoenix and Creighton University School of Medicine, Phoenix, AZ, Tampere University Hospital, Tays Cancer Centre and Nordic Society of Gynaecological Oncology (NSGO), Tampere, Finland, Division of Gynecologic Oncology, The Ohio State University, James Comprehensive Cancer Center, Columbus, OH, AOU Policlinico di Modena, Modena and Multicenter Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO), Modena, Italy, Division of Gynecologic Oncology, The University of Cincinnati Cancer, Cincinnati, OH, Centre Antoine Lacassagne, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers de l’Ovaire et du sein (GINECO), Nice, France, Gynecologic Oncology (GOG) and Departments of Obstetrics/Gynecology and Medicine, Division of Gynecologic Oncology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY, Charité Universitätsmedizin and Arbeitsgemeinschaft Gynäkologische Onkologi (AGO), Berlin, Germany, University of New Mexico, Albuquerque, NM, Hospital Clínico Universitario Lozano Blesa, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Zaragoza, Spain, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Wilmot Cancer Institute, University of Rochester Medical Center, University of Rochester, Rochester, NY, Centre Hospitalier Universitaire Université Catholique de Louvain Namur (Sainte-Elisabeth), Namur, Belgium, Herlev Hospital and Nordic Society of Gynaecological Oncology (NSGO), Herlev, Denmark, GSK, Philadelphia, PA, Medical Oncology Department, Cancer Center Clínica Universidad de Navarra, Madrid, Program in Solid Tumours, CIMA, Pamplona, and Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spain Abstract Disclosures Research Funding Pharmaceutical/Biotech Company GSK Background: Niraparib was approved as maintenance therapy for pts with advanced ovarian cancer (OC) after complete or partial response (CR/PR) to first-line (1L) platinum-based chemotherapy (CT) based on results from the PRIMA study. In this post hoc analysis, we identified factors associated with long-term PFS. Methods: PRIMA is a phase 3, randomized study of pts with newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer at high risk for relapse with CR/PR after 1L platinum-based CT. Pts were randomized 2:1 to niraparib 200 or 300 mg or placebo QD, and stratified by best response to 1L CT (CR/PR), neoadjuvant CT (yes/no), and homologous recombination deficiency (HRD) status (deficient [HRd]/proficient or not determined [HRp/nd]). Investigator-assessed PFS was dichotomized in niraparib-treated pts with progressive disease (PD)/censoring <2 years vs PD/censoring ≥2 years after randomization (data cut, Nov 17, 2021). Logistic regression modeling using backward elimination (significance level=0.15) was used to identify baseline covariates associated with long-term PFS. Results: Of 487 niraparib-treated pts, 152 (31%) had PD/censoring ≥2 years after randomization. Odds ratios (OR) for PFS ≥2 years by baseline subgroup are shown (Table). The logistic regression model showed that BRCA mutation and HRD status, International Federation of Gynecology and Obstetrics (FIGO) stage, fallopian tube as the site of the primary tumor, and absence of baseline nontarget lesions were associated with longer PFS. Eastern Cooperative Oncology Group (ECOG) performance score, body mass index, age, time from CT to randomization, number of target lesions, best response after CT, number of CT cycles, type of debulking surgery, and residual disease were not associated with PFS ≥2 years. Safety has been reported previously ( Ann Oncol. 2022;33[suppl 7]:S789). Conclusions: Results suggest that long-term PFS in pts treated with niraparib may be associated with BRCA/HRd biomarker status, FIGO stage, primary tumor site, and number of baseline non-target lesions. These data are hypothesis generating. Clinical trial information: NCT02655016. Variable OR a (95% CI) N=487 P Value BRCA /HRD status BRCA 1/HRd, n=105 BRCA 2/HRd, n=47 BRCA wt/nd + HRd, n=95 BRCA wt + HRp/nd,* n=240 3.73 (2.191–6.335) 10.75 (5.158–22.407) 2.49 (1.422–4.372) 1.00 <0.0001 <0.0001 0.0014 FIGO stage III, n=318 IV,* n=169 1.62 (1.019–2.568) 1.000 0.0412 Primary tumor site Primary peritoneal, n=34 Fallopian tube, n=65 Ovarian*, n=388 0.53 (0.208–1.332) 0.54 (0.275–1.052) 1.000 0.1755 0.0700 Baseline nontarget lesions 0, n=331 1, n=90 ≥2,* n=66 4.67 (2.076–10.485) 2.20 (0.857–5.649) 1.000 0.0002 0.1010 *Reference variable. a Higher OR indicates more likely to remain progression free; eg, OR of 1.63 is 63% more likely to remain progression free for ≥2 years vs reference. wt, wild type.

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