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.

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