Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial
Josep M Del Campo, Ursula A Matulonis, Susanne Malander, Diane Provencher, Sven Mahner, Philippe Follana, Justin Waters, Jonathan S Berek, Kathrine Woie, Amit M Oza, Ulrich Canzler, Marta Gil-Martin, Anne Lesoin, Bradley J Monk, Bente Lund, Lucy Gilbert, Robert M Wenham, Benedict Benigno, Sujata Arora, Sebastien J Hazard, Mansoor R Mirza, Josep M Del Campo, Ursula A Matulonis, Susanne Malander, Diane Provencher, Sven Mahner, Philippe Follana, Justin Waters, Jonathan S Berek, Kathrine Woie, Amit M Oza, Ulrich Canzler, Marta Gil-Martin, Anne Lesoin, Bradley J Monk, Bente Lund, Lucy Gilbert, Robert M Wenham, Benedict Benigno, Sujata Arora, Sebastien J Hazard, Mansoor R Mirza
Abstract
Purpose: In the ENGOT-OV16/NOVA trial (ClinicalTrials.gov identifier: NCT01847274), maintenance therapy with niraparib, a poly(ADP-ribose) polymerase inhibitor, prolonged progression-free survival in patients with platinum-sensitive, recurrent ovarian cancer who had a response to their last platinum-based chemotherapy. The objective of the study was to assess the clinical benefit and patient-reported outcomes in patients who had a partial response (PR) and complete response (CR) to their last platinum-based therapy.
Patients and methods: A total of 553 patients were enrolled in the trial. Of 203 patients with a germline BRCA mutation (gBRCAmut), 99 had a PR and 104 had a CR to their last platinum-based therapy; of 350 patients without a confirmed gBRCAmut (non-gBRCAmut), 173 had a PR and 177 had a CR. Post hoc analyses were carried out to evaluate safety and the risk of progression in these patients according to gBRCAmut status and response to their last platinum-based therapy. Ovarian cancer-specific symptoms and quality of life were assessed using the Functional Assessment of Cancer Therapy-Ovarian Symptom Index.
Results: Progression-free survival was improved in patients treated with niraparib compared with placebo in both the gBRCAmut cohort (PR: hazard ratio [HR], 0.24; 95% CI, 0.131 to 0.441; P < .0001; CR: HR, 0.30; 95% CI, 0.160 to 0.546; P < .0001) and the non-gBRCAmut cohort (PR: HR, 0.35; 95% CI, 0.230 to 0.532; P < .0001; CR: HR, 0.58; 95% CI, 0.383 to 0.868; P = .0082). The incidence of any-grade and grade 3 or greater adverse events was manageable. No meaningful differences were observed between niraparib and placebo in PR and CR subgroups with respect to patient-reported outcomes.
Conclusion: Patients achieved clinical benefit from maintenance treatment with niraparib regardless of response to the last platinum-based therapy.
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References
- Hanker LC, Loibl S, Burchardi N, et al. The impact of second to sixth line therapy on survival of relapsed ovarian cancer after primary taxane/platinum-based therapy. Ann Oncol. 2012;23:2605–2612.
- Ledermann JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24:vi24–vi32.
- Tapia G, Diaz-Padilla I. Molecular mechanisms of platinum resistance in ovarian cancer , in Diaz-Padilla I (ed): Ovarian Cancer: A Clinical and Translational Update. Rijeka, Croatia, InTechOpen, 2013, pp 205-223 .
- Ledermann JA, Sessa N, Colombo N, et al. eUpdate: Ovarian cancer treatment recommendations.
- National Comprehensive Cancer Network Clinical practice guidelines in oncology: Ovarian cancer, version 2.2018.
- Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1949–1961.
- Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375:2154–2164.
- Pujade-Lauraine E, Ledermann JA, Selle F, et al. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017;18:1274–1284.
- Beaumont J, Yount S, Lalla D, et al. Validation of the Functional Assessment of Cancer Therapy–Ovarian (FACT-O) Symptom Index (FOSI) in a phase II clinical trial of pertuzumab in patients with advanced ovarian cancer. J Clin Oncol. 25, 2007 (suppl; abstr 16021)
- Kayl AE, Meyers CA. Side-effects of chemotherapy and quality of life in ovarian and breast cancer patients. Curr Opin Obstet Gynecol. 2006;18:24–28.
Source: PubMed