Efficacy and safety of olaparib according to age in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer: Analysis of the phase III SOLO2/ENGOT-Ov21 study

Published:January 31, 2022DOI:


      • Olaparib maintenance in BRCA1/2-mutated PSOC results in time without toxicity of more than one year irrespective of age.
      • No significant age-dependent differences were detected in terms of efficacy, safety, and QoL with olaparib treatment.
      • Discontinuation rates for toxicity, frequency of AML/MDS, and no clear OS effects warrant close monitoring in older patients.



      Olaparib has significantly improved outcome and patient-centered endpoints in BRCA1/2-mutated patients with recurrent platinum-sensitive ovarian cancer (PSOC). Specific information on efficacy and safety of olaparib for older patients appears of special interest.


      295 patients from the SOLO2 trial randomly assigned to olaparib or placebo were categorized according to age-cutoff at 65 years. Efficacy, tolerability, and quality of life (QoL) of olaparib relative to placebo within in each age group was analyzed.


      Baseline characteristics were similar in patients ≥65 years (N = 62;21.0%) compared to patients <65 years (N = 233;78.9%). No significant difference in the magnitude of progression-free survival (PFS) benefit from olaparib for older patients (N = 40, hazard ratio [HR]≥65 0.43, 95%-confidence interval [CI] 0.24–0.81) as compared with younger patients (N = 155, HR<65 0.31 (95%-CI 0.22–0.43) was seen (interaction P = 0.33). The overall survival (OS)benefit seen in younger patients in the olaparib arm was not observed in older patients. Older and younger patients had comparable safety profiles and QoL scores although higher discontinuation rates for toxicity, and higher frequency of AML/MDS were noted in the older subset. TWiST analysis revealed clinically meaningful duration of good QoL on olaparib for both age groups (≥65: 13.5 vs <65: 18.4 months, P = 0.05).


      Results of this large phase III cohort of BRCA1/2-mutated PSOC patients treated with olaparib underline impressive efficacy of olaparib maintenance irrespective of age. Although toxicity and tolerability did not raise significant concerns, some caution, close monitoring, and follow-up needs to be exercised for older patients given higher discontinuation rates, frequency of AML/MDS, and no clear effects on OS.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Gynecologic Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Wilson M.K.
        • Pujade-Lauraine E.
        • Aoki D.
        • et al.
        Fifth ovarian cancer consensus conference of the Gynecologic Cancer InterGroup: recurrent disease.
        Ann. Oncol. 2017; 28: 727-732
        • Ledermann J.
        • Harter P.
        • Gourley C.
        • et al.
        Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.
        N. Engl. J. Med. 2012; 366: 1382-1392
        • Ledermann J.
        • Harter P.
        • Gourley C.
        • et al.
        Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial.
        Lancet Oncol. 2014; 15: 852-861
        • Mirza M.R.
        • Monk B.J.
        • Herrstedt J.
        • et al.
        Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer.
        N. Engl. J. Med. 2016; 375: 2154-2164
        • Coleman R.L.
        • Oza A.M.
        • 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
        • Pujade-Lauraine E.
        • Ledermann J.A.
        • 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
        • Poveda A.
        • Floquet A.
        • Ledermann J.A.
        • et al.
        Olaparib tablets as maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a final analysis of a double-blind, randomised, placebo-controlled, phase 3 trial.
        Lancet Oncol. 2021; 22: 620-631
        • Howlader N.
        • Noone A.M.
        • Krapcho M.
        • et al.
        SEER Cancer Statistics Review, 1975-2014.
        National Cancer Institute, Bethesda, MD2018
        • Hilpert F.
        • du Bois A.
        • Greimel E.R.
        • et al.
        Feasibility, toxicity and quality of life of first-line chemotherapy with platinum/paclitaxel in elderly patients aged >or=70 years with advanced ovarian cancer--a study by the AGO OVAR Germany.
        Ann. Oncol. 2007; 18: 282-287
        • Hauke J.
        • Hahnen E.
        • Schneider S.
        • et al.
        Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883).
        J. Med. Genet. 2019; 56: 574-580
        • VanderWalde N.
        • Jagsi R.
        • Dotan E.
        • et al.
        NCCN guidelines insights: older adult oncology, version 2.2016.
        J. Natl. Compr. Cancer Netw. 2016; 14: 1357-1370
        • Friedlander M.
        • Gebski V.
        • Gibbs E.
        • et al.
        Health-related quality of life and patient-centred outcomes with olaparib maintenance after chemotherapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT Ov-21): a placebo-controlled, phase 3 randomised trial.
        Lancet Oncol. 2018; 19: 1126-1134
        • Ledermann J.A.
        • Harter P.
        • Gourley C.
        • et al.
        Quality of life during olaparib maintenance therapy in platinum-sensitive relapsed serous ovarian cancer.
        Br. J. Cancer. 2016; 115: 1313-1320
        • Bouchardy C.
        • Rapiti E.
        • Blagojevic S.
        • et al.
        Older female cancer patients: importance, causes, and consequences of undertreatment.
        J. Clin. Oncol. 2007; 25: 1858-1869
        • Fourcadier E.
        • Tretarre B.
        • Gras-Aygon C.
        • et al.
        Under-treatment of elderly patients with ovarian cancer: a population based study.
        BMC Cancer. 2015; 15: 937
        • Pignata S.
        • Ferrandina G.
        • Scarfone G.
        • et al.
        Poor outcome of elderly patients with platinum-sensitive recurrent ovarian cancer: results from the SOCRATES retrospective study.
        Crit. Rev. Oncol. Hematol. 2009; 71: 233-241
        • Hilpert F.
        • Wimberger P.
        • du Bois A.
        • et al.
        Treatment of elderly ovarian cancer patients in the context of controlled clinical trials: a joint analysis of the AGO Germany experience.
        Onkologie. 2012; 35: 76-81
        • Falandry C.
        • Savoye A.M.
        • Stefani L.
        • et al.
        EWOC-1: a randomized trial to evaluate the feasibility of three different first-line chemotherapy regimens for vulnerable elderly women with ovarian cancer (OC): a GCIG-ENGOT-GINECO study.
        J. Clin. Oncol. 2019; 37: 5508
        • Dockery L.E.
        • Tew W.P.
        • Ding K.
        • et al.
        Tolerance and toxicity of the PARP inhibitor olaparib in older women with epithelial ovarian cancer.
        Gynecol. Oncol. 2017; 147: 509-513
        • Trillsch F.
        • Woelber L.
        • Eulenburg C.
        • et al.
        Treatment reality in elderly patients with advanced ovarian cancer: a prospective analysis of the OVCAD consortium.
        J. Ovarian Res. 2013; 6: 42
        • Kuchenbaecker K.B.
        • Hopper J.L.
        • Barnes D.R.
        • et al.
        Risks of breast, ovarian, and contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
        JAMA. 2017; 317: 2402-2416
        • Fabbro M.
        • Moore K.N.
        • Dorum A.
        • et al.
        Efficacy and safety of niraparib as maintenance treatment in older patients (>/=70years) with recurrent ovarian cancer: results from the ENGOT-OV16/NOVA trial.
        Gynecol. Oncol. 2019; 152: 560-567
        • Matulonis U.A.
        • Walder L.
        • Nottrup T.J.
        • et al.
        Niraparib maintenance treatment improves time without symptoms or toxicity (TWiST) versus routine surveillance in recurrent ovarian cancer: a TWiST analysis of the ENGOT-OV16/NOVA trial.
        J. Clin. Oncol. 2019; 37: 3183-3191
        • van Dongen-Leunis A.
        • Redekop W.K.
        • Uyl-de Groot C.A.
        Which questionnaire should be used to measure quality-of-life utilities in patients with acute leukemia? An evaluation of the validity and interpretability of the EQ-5D-5L and preference-based questionnaires derived from the EORTC QLQ-C30.
        Value Health. 2016; 19: 834-843
        • Rowen D.
        • Young T.
        • Brazier J.
        • et al.
        Comparison of generic, condition-specific, and mapped health state utility values for multiple myeloma cancer.
        Value Health. 2012; 15: 1059-1068
        • Bhat G.
        • Karakasis K.
        • Oza A.M.
        Measuring quality of life in ovarian cancer clinical trials-can we improve objectivity and cross trial comparisons?.
        Cancers (Basel). 2020; 12
        • Sehouli J.
        • Tome O.
        • Dimitrova D.
        • et al.
        A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO).
        J. Cancer Res. Clin. Oncol. 2017; 143: 541-550
        • Havrilesky L.J.
        • Alvarez Secord A.
        • Ehrisman J.A.
        • et al.
        Patient preferences in advanced or recurrent ovarian cancer.
        Cancer. 2014; 120: 3651-3659
        • Morice P.M.
        • Leary A.
        • Dolladille C.
        • et al.
        Myelodysplastic syndrome and acute myeloid leukaemia in patients treated with PARP inhibitors: a safety meta-analysis of randomised controlled trials and a retrospective study of the WHO pharmacovigilance database.
        Lancet Haematol. 2021; 8: e122-e134
        • Ma X.
        • Does M.
        • Raza A.
        • et al.
        Myelodysplastic syndromes: incidence and survival in the United States.
        Cancer. 2007; 109: 1536-1542
        • Shenolikar R.
        • Durden E.
        • Meyer N.
        • et al.
        Incidence of secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in patients with ovarian or breast cancer in a real-world setting in the United States.
        Gynecol. Oncol. 2018; 151: 190-195