4350 - Time to second progression (PFS2) and second subsequent therapy (TSST) for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm) treated with maintenance (mt) olaparib (ola) – Phase III SOLO1 trial

Background

SOLO1 (NCT01844986; GOG-3004) pts with newly diagnosed, advanced OC and a BRCAm treated with mt ola had a substantial progression-free survival benefit vs placebo (pbo) (HR 0.30 [95% CI 0.23–0.41], P < 0.001; Moore et al. NEJM 2018). The impact of first line use of PARP inhibitors (PARPi) on subsequent therapy is of clinical interest. Secondary objectives included PFS2 and TSST, which indicate the effect of treatment beyond first progression.

Methods

Pts were randomized 2:1 to ola 300 mg bid or pbo for up to 2 years or until disease progression. After first progression, PFS2 was assessed every 12 weeks (radiological, CA125 or clinical progression).

Results

There were 121 PFS2 events (HR 0.50, 95% CI 0.35–0.72, median PFS2 was not reached (NR) [ola] vs 41.9 months [m; pbo]). Median TSST was NR (ola) vs 40.7 m (pbo; HR 0.45, 95% CI 0.32–0.63). Based on Kaplan-Meier estimates, at 36 m, the proportions of ola pts free from second progression or second therapy were 15 and 18 percentage points higher respectively, than the proportions of pbo pts (Table).Table: 995PD

Of 198 pts who progressed, 91/102 in the ola arm and 94/96 in the pbo arm had a subsequent therapy or therapies: the most common therapies were platinum (plat)-based chemotherapy (chemo) (n = 58 [64%] vs n = 50 [53%]), including plat with bevacizumab (bev) (n = 22 [24%] vs n = 15 [16%]); PARPi, including plat followed by PARPi (n = 20 [22%] vs n = 49 [52%]); and non-plat chemo (excluding regimens with bev) (n = 35 [38%] vs n = 26 [28%]). In the ola arm, 10 pts had ola as part of their first subsequent therapy (9 had ola as mt following plat-based chemo) and 3 progressed for a second time. In the pbo arm, 44 (47%) pts who had subsequent therapy had ola outside the study.

Conclusions

Mt ola increases both PFS2 and TSST vs pbo. The benefit of mt ola in newly diagnosed OC continues beyond first progression.

Clinical trial identification

NCT01844986.

Editorial acknowledgement

Laura Smart, from Mudskipper Business, Ltd, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Legal entity responsible for the study

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Funding

AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, U.S.A. (MSD).

Disclosure

A. Oaknin: Advisory / Consultancy: Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab. K. Moore: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Immunogen; Advisory / Consultancy: VBL Therapeutics; Advisory / Consultancy: Merck; Advisory / Consultancy: Janssen; Advisory / Consultancy: Aravive; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Eisai; Advisory / Consultancy: Samumed; Advisory / Consultancy: Oncomed. N. Colombo: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Tesaro; Honoraria (self), Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Pfizer. M. Friedlander: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: MSD; Advisory / Consultancy: Lilly; Advisory / Consultancy: Takeda; Non-remunerated activity/ies: AbbVie. A. Floquet: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self), Advisory / Consultancy: Tesaro. A. Leary: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Biocad; Advisory / Consultancy: Seattle Genetics. G.S. Sonke: Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Roche; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis. C. Gourley: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Tesaro; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): 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 (self): Novartis; Research grant / Funding (self): Aprea. S. Banerjee: Honoraria (self), Research grant / Funding (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. A.M. Oza: Non-remunerated activity/ies, Steering committee: AstraZeneca; Non-remunerated activity/ies, Steering committee: Clovis Oncology; Non-remunerated activity/ies, Steering committee: Tesaro. A. González-Martín: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab; Advisory / Consultancy: MSD; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar. C. Aghajanian: Honoraria (self): Tesaro; Honoraria (self): ImmunoGen; Honoraria (self): Clovis Oncology. E.S. Lowe: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. R. Bloomfield: 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.