811MO - Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1

Background

Newly diagnosed advanced OC pts are at high risk of relapse and 5-y survival is 30–50%. Delay of recurrence, prolonged survival and, for some patients, increased chance of cure are goals of treatment in this setting. In SOLO1 (NCT01844986; GOG-3004) pts with OC and a BRCAm who were in response after first-line platinum-based chemotherapy derived significant progression-free survival (PFS) benefit from maintenance olaparib vs placebo (pbo; median 41 months [m] f/u; median not reached vs 13.8 m; HR 0.30; P<0.001; Moore et al. NEJM 2018). We report data from 5-y f/u (data cut-off 5 March 2020).

Methods

Pts received maintenance olaparib (tablets; 300 mg bid) or pbo for up to 2 y or until progression. PFS and recurrence-free survival (RFS) were investigator-assessed by modified RECIST v1.1. For pts in complete response (CR) at baseline, RFS was defined post hoc as time from randomization to disease recurrence (new lesions by imaging) or death.

Results

260 pts were randomized to olaparib; 131 to pbo (median treatment duration 24.6 vs 13.9 m, respectively). After a median of 4.8 and 5.0 y of f/u, median PFS was 56 vs 14 m (Table). Among pts in CR at baseline, risk of disease recurrence or death was reduced by 63%. Additional secondary endpoints will be reported. Table: 811MO

*Pts had CR at baseline based on electronic case report form data.^†Kaplan–Meier estimates. CI, confidence interval; HR, hazard ratio; NR, not reachedThe safety profile of olaparib was consistent with previous observations. No new cases of myelodysplastic syndrome or acute myeloid leukaemia were reported and incidence of new primary malignancies remained balanced between arms (olaparib, 7/260 [3%]; pbo, 5/130 [4%]).

Conclusions

For pts with a BRCAm and newly diagnosed advanced OC the benefit derived from 2 y of maintenance olaparib was sustained beyond the end of treatment and after 5 y almost half of pts were progression-free vs 20% with pbo. Over 50% of pts in CR after first-line platinum-based chemotherapy remained free from relapse 5 y later. 5-y f/u is the longest for any PARP inhibitor in this setting and no new safety signals were observed.

Clinical trial identification

NCT01844986.

Editorial acknowledgement

Medical writing assistance was provided by Elin Pyke, MChem, Mudskipper Business Limited, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A.

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

Disclosure

S. Banerjee: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Clovis Oncology; Honoraria (self): Merck; Honoraria (self): PharmaMar; Honoraria (self): Roche; Honoraria (self): Seattle Genetics; Honoraria (self): Nucana. K.N. Moore: Advisory/Consultancy: AbbVie; Advisory/Consultancy: Aravive; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy, Research grant/Funding (self): GSK/Tesaro; Advisory/Consultancy: Genentech/Roche; Advisory/Consultancy: Immunogen; Advisory/Consultancy: Mersana; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy: Myriad; Advisory/Consultancy: Terveda; Advisory/Consultancy: VBL Therapeutics; Research grant/Funding (self): PTC Therapeutics; Research grant/Funding (self): Lilly. N. Colombo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Pfizer. A. Oaknin: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: PharmaMar; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Tesaro; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy: Genmab. M. Friedlander: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Beigene; Advisory/Consultancy: MSD; Advisory/Consultancy: Lilly; Advisory/Consultancy: Takeda; Non-remunerated activity/ies: AbbVie. A. Floquet: Advisory/Consultancy, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy: GSK; Advisory/Consultancy, Travel/Accommodation/Expenses, Non-remunerated activity/ies: MSD; Travel/Accommodation/Expenses, Non-remunerated activity/ies: Roche. A. Leary: Honoraria (self), Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Clovis Oncology; Advisory/Consultancy: Biocad; Advisory/Consultancy: Seattle Genetics. G.S. Sonke: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Roche. C. Gourley: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Tesaro; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Nucana; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Clovis Oncology; Honoraria (self), Advisory/Consultancy: Foundation One; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Sierra Oncology; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Aprea. A. Oza: Non-remunerated activity/ies: AstraZeneca; Non-remunerated activity/ies: Clovis Oncology; Non-remunerated activity/ies: Tesaro. A. González Martín: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Non-remunerated activity/ies, Principal investigator of PRIMA study sponsored by Tesaro: Tesaro; Advisory/Consultancy: Clovis; Advisory/Consultancy: Pfizer/Merck; Advisory/Consultancy: ImmunoGen; Advisory/Consultancy, Speaker Bureau/Expert testimony: PharmaMar; Advisory/Consultancy: MSD; Advisory/Consultancy: Genmab; Advisory/Consultancy: Oncoinvent; Officer/Board of Directors, Chairman GEICO (Grupo Español Investigación Cáncer de Ovario): GEICO; Officer/Board of Directors, Chairman ENGOT (European Network for Gynecological Oncologic Trials): ENGOT. C. Aghajanian: Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): AbbVie; Advisory/Consultancy, Research grant/Funding (institution): Clovis; Advisory/Consultancy: Eisai/Merck; Advisory/Consultancy: ImmunoGen, Inc.; Advisory/Consultancy: Mersana; Advisory/Consultancy: Roche; Advisory/Consultancy: Tesaro. W. Bradley: Advisory/Consultancy: Inovio. E. Holmes: Full/Part-time employment: AstraZeneca. E.S. Lowe: Shareholder/Stockholder/Stock options, Full/Part-time employment: AstraZeneca. P. DiSilvestro: Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Tesaro. All other authors have declared no conflicts of interest.