Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial.
[en] [en] OBJECTIVE: To analyze the safety and efficacy of niraparib in patients aged ≥70 years with recurrent ovarian cancer in the ENGOT-OV16/NOVA trial.
METHODS: The trial enrolled 2 independent cohorts with histologically diagnosed recurrent ovarian, fallopian tube, or peritoneal cancer who responded to platinum rechallenge, on the basis of germline breast cancer susceptibility gene mutation (gBRCAmut) status. Patients were randomized 2:1 to receive niraparib (300 mg) or placebo once daily until disease progression. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Adverse events (AEs) of special interest were based on the known safety profile of poly(ADP-ribose) polymerase inhibitors.
RESULTS: Patients aged ≥70 years in the gBRCAmut cohort receiving niraparib (n = 14) had not yet reached a median PFS compared with a median PFS of 3.7 months for the same age group in the placebo arm (hazard ratio [HR], 0.09 [95% confidence interval (CI), 0.01 to 0.73]). Non-gBRCAmut patients aged ≥70 years receiving niraparib (n = 47) had a median PFS of 11.3 months compared with 3.8 months in the placebo arm (HR, 0.35 [95% CI, 0.18 to 0.71]). Median duration of follow-up in the niraparib arm was 17.3 months in patients ≥70 years and 17.2 months in patients <70 years. Frequency, severity of AEs, and dose reductions in the niraparib arm were similar in patients aged <70 and ≥ 70 years population. The most common grade ≥ 3 AEs in patients ≥70 years were hematologic: thrombocytopenia event (34.4%), anemia event (13.1%), and neutropenia event (16.4%).
CONCLUSIONS: For patients ≥70 years of age receiving niraparib as maintenance treatment in the ENGOT-OV16/NOVA trial, PFS benefits and incidence of any grade or serious treatment-emergent AEs were comparable to results in the younger population. Use of niraparib should be considered in this population.
Disciplines :
Oncology
Author, co-author :
Fabbro, Michel ; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Paris, France, Institut du Cancer de Montpellier, Montpellier, France. Electronic address: michel.fabbro@icm.unicancer.fr
Moore, Kathleen N; Stephenson Cancer Center, University of Oklahoma HSC, Oklahoma City, OK, USA, Sarah Cannon Research Institute, Nashville, TN, USA
Dørum, Anne; Nordic Society of Gynaecological Oncology (NSGO), Copenhagen, Denmark, Radiumhospitalet, Oslo University Hospital, Oslo, Norway
Tinker, Anna V; BC Cancer Agency, Vancouver, BC, Canada
Mahner, Sven; Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Taufkirchen, Germany, Department of Gynecology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Department of Obstetrics and Gynecology, University Hospital Munich, Ludwig-Maximilians-University of Munich, Munich, Germany
Bover, Isabel; Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spain, Hospital Son Llàtzer, Palma de Mallorca, Spain
Banerjee, Susana; National Cancer Research Institute (NCRI), London, United Kingdom, The Royal Marsden NHS Foundation Trust, London, United Kingdom
Tognon, Germana; Division of Obstetrics and Gynecology, ASST Spedali Civili di Brescia, Brescia, Italy
Goffin, Frédéric ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gynécologie-obstétrique (CHR)
Shapira-Frommer, Ronnie; Israeli Society of Gynecologic Oncology (ISGO), Hadera, Israel, Sheba Medical Center, Ramat Gan, Israel
Wenham, Robert M; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
Hellman, Kristina; Nordic Society of Gynaecological Oncology (NSGO), Copenhagen, Denmark, Karolinska University Hospital, Stockholm, Sweden
Provencher, Diane; Centre Hospitalier de L'Université de Montréal (CHUM), Montreal, QC, Canada
Harter, Philipp; Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Taufkirchen, Germany, Department of Gynecology & Gynecologic Oncology, Kliniken Essen-Mitte, Essen, Germany
Vázquez, Isabel Palacio; Grupo Español de Investigación en Cáncer de Ovario (GEICO), Madrid, Spain, Hospital Universitario Central de Asturias, Oviedo, Spain
Follana, Philippe; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Paris, France, Centre Antoine Lacassagne, Nice, France
Pineda, Mario J; Northwestern University, Chicago, IL, USA
Mirza, Mansoor R; Nordic Society of Gynaecological Oncology (NSGO), Copenhagen, Denmark, Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark
Hazard, Sebastien J; TESARO, Inc., Waltham, MA, USA
Matulonis, Ursula A; Dana-Farber Cancer Institute, Boston, MA, USA
Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial.
American Cancer Society, Key Statistics for Ovarian Cancer. 2018 https://www.cancer.org/cancer/ovarian-cancer/about/key-statistics.html#references. (Accessed 1 June 2018)
Howlader, N., Noone, A.M., Krapcho, M., Miller, D., Bishop, K., Kosary, C.L., et al. (eds.) SEER Cancer Statistics Review, 1975-2014, National Cancer Institute, 2017, Bethesda, MD https://seer.cancer.gov/csr/1975_2014/.
Thigpen, T., Brady, M.F., Omura, G.A., Creasman, W.T., McGuire, W.P., Hoskins, W.J., et al. Age as a prognostic factor in ovarian carcinoma: the gynecologic oncology group experience. Cancer 71 (1993), 606–614.
Freyer, G., Tew, W.P., Moore, K.N., Treatment and trials: ovarian cancer in older women. Am. Soc. Clin. Oncol. Educ. Book, 2013, 227–235.
Tinquaut, F., Freyer, G., Chauvin, F., Gane, N., Pujade-Lauraine, E., Falandry, C., Prognostic factors for overall survival in elderly patients with advanced ovarian cancer treated with chemotherapy: results of a pooled analysis of three GINECO phase II trials. Gynecol. Oncol. 143 (2016), 22–26.
Uyar, D., Frasure, H.E., Markman, M., von Gruenigen, V.E., Treatment patterns by decade of life in elderly women (≥70 years of age) with ovarian cancer. Gynecol. Oncol. 98 (2005), 403–408.
Gibson, S.J., Fleming, G.F., Temkin, S.M., Chase, D.M., The application and outcome of standard of care treatment in elderly women with ovarian cancer: a literature review over the last 10 years. Front. Oncol., 6, 2016, 63.
Hilpert, F., du Bois, A., Greimel, E.R., Hedderich, J., Krause, G., Venhoff, L., et al. Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged ≥70 years with advanced ovarian cancer–a study by the AGO OVAR Germany. Ann. Oncol. 18 (2007), 282–287.
von Gruenigen, V.E., Huang, H.Q., Beumer, J.H., Lankes, H.A., Tew, W., Herzog, T., et al. Chemotherapy completion in elderly women with ovarian, primary peritoneal or fallopian tube cancer–an. NRG Oncology/Gynecologic Oncology Group study Gynecol. Oncol., 144, 2017, 459–467.
National Comprehensive Cancer Network (NCCN), NCCN Clinical Practice Guidelines in Oncology: Senior Adult Oncology. V2.2017 ed2017.
Mirza, M.R., Monk, B.J., Herrstedt, J., Oza, A.M., Mahner, S., Redondo, A., et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N. Engl. J. Med. 375 (2016), 2154–2164.
Dumas, L., Ring, A., Butler, J., Kalsi, T., Harari, D., Banerjee, S., Improving outcomes for older women with gynaecological malignancies. Cancer Treat. Rev. 50 (2016), 99–108.
Balducci, L., Extermann, M., Management of cancer in the older person: a practical approach. Oncologist 5 (2000), 224–237.
Dockery, L.E., Tew, W.P., Ding, K., Moore, K.N., Tolerance and toxicity of the PARP inhibitor olaparib in older women with epithelial ovarian cancer. Gynecol. Oncol. 147 (2017), 509–513.
Schram, A.M., Aghajanian, C.A., Hyman, D.M., Niraparib in recurrent ovarian cancer. N. Engl. J. Med. 376 (2017), 801–802.
Feng, Z., Hu, W., Teresky, A.K., Hernando, E., Cordon-Cardo, C., Levine, A.J., Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 16633–16638.
