Dana Chase, MD, FACOG


Associate Professor
Creighton University
University of Arizona College of Medicine
Gynecologic Oncologist, Arizona Oncology

Maintenance olaparib for patients with newly diagnosed, advanced ovarian cancer and a BRCA mutation: 5-year follow-up from SOLO1
W. Bradley, 2021. Society of Gynecologic Oncology Virtual Meeting, March 2021.

KOL Insight and Perspective

Updates in PARP inhibitor Research in Ovarian Cancer: Results presented at the Annual Society of Gynecology Oncology Meeting 2021

Background: PARP inhibitor therapy is currently approved for use in multiple different lines of treatment for ovarian cancer patients.   There are indications for maintenance in platinum-sensitive recurrent patients regardless of biomarker status as well as for treatment in BRCA-mutated patients after multiple lines of therapy.(1-7)  More recently there are several studies using PARP inhibitor therapy as maintenance after frontline treatment in women, biomarker or no biomarker (1-7).  Despite the publication of these data, follow up questions regarding long term data, safety and eligibility.  Several follow up studies were presented at the most recent Society of Gynecology Oncology Meeting in March 2021.

Results: Bradley et al presented 5 year follow up data from SOLO1, a study of maintenance Olaparib after front-line platinum treatment for metastatic BRCA-mutated ovarian cancer.  In this presentation, those patients treated with Olaparib maintenance demonstrated a 56-month median PFS versus 13.8 months in women given placebo.  The benefit of Olaparib maintenance clearly persisted past the 2-year treatment cap.  Furthermore, the benefit was seen in both lower and higher risk groups.  For example, in the lower risk group, median PFS was not even reached at 5 years of follow up, compared with 21.9 months in the placebo group.  Lower risk disease excludes patients with neoadjuvant chemotherapy and has very few patients with residual disease after surgery (<10%).   Of note, there were no new cases of MDS/AML reported.  Pujade-Lauraine et al presented follow up data exploring the use of biomarkers in patients treated with maintenance Olaparib with bevacizumab on the PAOLA-1/ENGOT-ov25 study.  Current approvals suggest using the regimen only in women with Homologous Recombination Deficient (HRD) ovarian cancer.  This perhaps conflicts real-world practice where many practitioners utilize gene panel testing to explore Homologous Recombination Repair (HRR) gene mutations which then is used to direct PARPi usage.  In this study, the authors revealed that HRR mutation (excluding BRCA) was not predictive of PFS benefit.  Matulonis et al presented long term follow-up data for the ENGOT-OV16/NOVA trial of niraparib maintenance in platinum-sensitive recurrent ovarian cancer.  Benefit was demonstrated in patients who had exposure to this regimen beyond first progression (PFS2).  Although not statistically significant (and complicated by crossover with PARPi use after study completed), there was a trend towards overall survival benefit in the BRCA mutated cohort (not identified in the non-BRCA mutated group).  Of interest, the incidence of MDS/AML remained low in the long-term follow up data at 3.5% in the niraparib arm.

Conclusions: The data presented above further demonstrates the benefit and safety of PARPi use in ovarian cancer patients

Clinical Implications: Recognizing extended benefit beyond usage of PARPi therapy with continued safety should further motivate oncologists to offer this therapy to patients.

  1. Mirza MR, Monk BJ, Herrstedt J, Oza AM, Mahner S, Redondo A, Fabbro M, Ledermann JA, Lorusso D, Vergote I, Ben-Baruch NE, Marth C, Mądry R, Christensen RD, Berek JS, Dørum A, Tinker AV, du Bois A, González-Martín A, Follana P, Benigno B, Rosenberg P, Gilbert L, Rimel BJ, Buscema J, Balser JP, Agarwal S, Matulonis UA; ENGOT-OV16/NOVA Investigators. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med. 2016 Dec 1;375(22):2154-2164. doi: 10.1056/NEJMoa1611310. Epub 2016 Oct 7. PMID: 27717299.
  2. Pujade-Lauraine E, Ledermann JA, Selle F, Gebski V, Penson RT, Oza AM, Korach J, Huzarski T, Poveda A, Pignata S, Friedlander M, Colombo N, Harter P, Fujiwara K, Ray-Coquard I, Banerjee S, Liu J, Lowe ES, Bloomfield R, Pautier P; SOLO2/ENGOT-Ov21 investigators. 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 Sep;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2. Epub 2017 Jul 25. Erratum in: Lancet Oncol. 2017 Sep;18(9):e510. PMID: 28754483.
  3. Penson RT, Valencia RV, Cibula D, Colombo N, Leath CA 3rd, Bidziński M, Kim JW, Nam JH, Madry R, Hernández C, Mora PAR, Ryu SY, Milenkova T, Lowe ES, Barker L, Scambia G. Olaparib Versus Nonplatinum Chemotherapy in Patients With Platinum-Sensitive Relapsed Ovarian Cancer and a Germline BRCA1/2 Mutation (SOLO3): A Randomized Phase III Trial. J Clin Oncol. 2020 Apr 10;38(11):1164-1174. doi: 10.1200/JCO.19.02745. Epub 2020 Feb 19. PMID: 32073956; PMCID: PMC7145583.
  4. Coleman RL, Oza AM, Lorusso D, Aghajanian C, Oaknin A, Dean A, Colombo N, Weberpals JI, Clamp A, Scambia G, Leary A, Holloway RW, Gancedo MA, Fong PC, Goh JC, O'Malley DM, Armstrong DK, Garcia-Donas J, Swisher EM, Floquet A, Konecny GE, McNeish IA, Scott CL, Cameron T, Maloney L, Isaacson J, Goble S, Grace C, Harding TC, Raponi M, Sun J, Lin KK, Giordano H, Ledermann JA; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Oct 28;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6. Epub 2017 Sep 12. Erratum in: Lancet. 2017 Oct 28;390(10106):1948. PMID: 28916367; PMCID: PMC5901715.
  5. Moore K, Colombo N, Scambia G, Kim BG, Oaknin A, Friedlander M, Lisyanskaya A, Floquet A, Leary A, Sonke GS, Gourley C, Banerjee S, Oza A, González-Martín A, Aghajanian C, Bradley W, Mathews C, Liu J, Lowe ES, Bloomfield R, DiSilvestro P. Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2018 Dec 27;379(26):2495-2505. doi: 10.1056/NEJMoa1810858. Epub 2018 Oct 21. PMID: 30345884.
  6. González-Martín A, Pothuri B, Vergote I, DePont Christensen R, Graybill W, Mirza MR, McCormick C, Lorusso D, Hoskins P, Freyer G, Baumann K, Jardon K, Redondo A, Moore RG, Vulsteke C, O'Cearbhaill RE, Lund B, Backes F, Barretina-Ginesta P, Haggerty AF, Rubio-Pérez MJ, Shahin MS, Mangili G, Bradley WH, Bruchim I, Sun K, Malinowska IA, Li Y, Gupta D, Monk BJ; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2391-2402. doi: 10.1056/NEJMoa1910962. Epub 2019 Sep 28. PMID: 31562799.
  7. Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. doi: 10.1056/NEJMoa1911361. PMID: 31851799.