Abstract 739P
Background
The randomized phase III PAOLA-1 study (NCT02477644) showed that addition of olaparib to bev maintenance improved progression-free survival (PFS) in pts with advanced OC (Ray-Coquard et al. NEJM 2019). We evaluated maintenance olaparib plus bev in the older subgroup of PAOLA-1 pts.
Methods
We collected clinical and molecular data from older pts (≥65 y). PFS in older pts was compared with younger pts (<65 y) and predictive factors explored. Safety was assessed in these subgroups.
Results
Of 806 randomized pts, 292 (36%) were ≥65 y (Table). Median age: older pts, 69 y (range 65–87 y); younger pts, 56 y (range 26–64 y). A lower proportion of older vs younger pts had an ECOG performance status of 0 (62% vs 75%), upfront surgery (39% vs 57%) and, of pts who had upfront surgery, a lower proportion had complete macroscopic resection (54% vs 62%). Older pts were less likely to have a BRCA1/2 mutation (BRCAm) (17% vs 36% of younger pts) or a homologous recombination deficiency (HRD)-positive status (36% vs 55%) and were more likely to be HRD-negative (46% vs 28%). Data cut off was 22 March 2019. After a median follow-up (in censored pts) of 22.1 months (mo) in older pts and 24.0 mo in younger pts, similar PFS was observed in the older and younger pt subgroups (Table). In older pts, greater PFS benefits with olaparib were seen in those with a BRCAm or who were HRD-positive. Incidence of grade ≥3 adverse events (AEs) was 64% in older pts (olaparib arm, 65% vs placebo arm, 62%) and 50% in younger pts (52% vs 46%). In the olaparib arm, there was one treatment-related AE with an outcome of death (in a younger pt) and three cases of myelodysplastic syndrome (1 older pt; 2 younger pts). Table: 739P
| Subgroups | Pts, n | Olaparib + bev (N=537) | Placebo + bev (N=269) | |
| ≥65 y | 292 | 205 (38%) | 87 (32%) | |
| <65 y | 514 | 332 (62%) | 182 (68%) | |
| Median PFS, mo | HR (95% CI) | |||
| ≥65 y | 292 | 21.6 | 16.6 | 0.55 (0.41–0.75) |
| <65 y | 514 | 22.9 | 16.9 | 0.61 (0.49–0.77) |
| ≥65 y subgroup (n=292) | ||||
| HRD positive | 104 | NE | 16.7 | 0.21 (0.12–0.39) |
| BRCAm | 51 | NE | 20.3 | 0.22 (0.07–0.62) |
| HRD positive/BRCA wt | 51 | NE | 16.5 | 0.23 (0.10–0.52) |
| HRD negative | 133 | 16.6 | 16.5 | 0.80 (0.52–1.25) |
| Complete debulking surgery* | 157 | NE | 18.8 | 0.43 (0.27–0.69) |
| Residual disease after surgery or no surgery | 135 | 16.6 | 11.4 | 0.67 (0.45–1.01) |
∗Including primary and interval debulking surgery; BRCA wt, BRCA wild type; CI, confidence interval; HR, hazard ratio; NE, not evaluable.
.Conclusions
Despite a lower rate of complete surgical debulking, older pts achieved a similar PFS benefit vs younger pts (including in the BRCAm and both HRD positive cohorts) when olaparib was added to first-line maintenance bev, with a comparable safety profile.
Clinical trial identification
NCT02477644.
Editorial acknowledgement
Editorial assistance was provided by Esmie Wescott, PhD, from Mudskipper Business Limited, funded by AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Legal entity responsible for the study
AstraZeneca.
Funding
ARCAGY Research, AstraZeneca, Merck & Co., Inc. and Hoffmann-La Roche Ltd.
Disclosure
R. Sabatier: Financial Interests, Personal, Research Grant: ESAI and AstraZeneca; Financial Interests, Personal, Advisory Role: GSK, Pfizer, Roche and Novartis; Non-Financial Interests, Personal, Other: Pfizer, Roche, GSK, Novartis and AstraZeneca. F. Joly: Financial Interests, Personal, Invited Speaker, Advisory board: GSK, Clovis, AstraZeneca, Janssen, BMS, MSD, Astellas, Sanofi, Ipsen, Amgen; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, Astellas; Non-Financial Interests, Personal, Leadership Role: GSK, Clovis, Janssen, BMS; Non-Financial Interests, Personal, Advisory Role: GSK, Clovis, Janssen, BMS. E.M. Guerra-Alia: Financial Interests, Personal, Advisory Role, advisory or consultancy honorarium: AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche; Financial Interests, Personal, Expert Testimony: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, PharmaMar, Roche, GSK; Financial Interests, Personal, Other, Travel grant: Roche, Tesaro, a GSK Company and Baxter. G. Bogner: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche and GSK; Financial Interests, Personal, Funding, Medical conferences: AstraZeneca, Roche and GSK. I. Vergote: Financial Interests, Institutional, Advisory Role: Amgen, AstraZeneca, Clovis Oncology, Carrick Therapeutics, Deciphera Pharmaceuticals, Elevar Therapeutics, F Hoffmann-La Roche, Genmab, GSK, Immunogen, Jazzpharma, Mersana, Millenium Pharmaceuticals, Merck, Novocure, Octimet Oncology NV, Oncoinvent AS, S; Financial Interests, Personal, Other, Research contract: Oncoinvent AS and Genmab; Financial Interests, Personal, Sponsor/Funding: Amgen and Roche; Financial Interests, Personal, Other, Travel grant: Amgen, Merck, Roche, AstraZeneca and Tesaro. N. Colombo: Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro and PharmaMar; Financial Interests, Personal, Advisory Role: Roche/Genentech, PharmaMar, AstraZeneca, Clovis Oncology, Pfizer, Merck Oncology, Takeda, Tesaro, and BioCadand GSK. S. Hietanen: Financial Interests, Personal, Advisory Board: GSK and AstraZeneca. U. Canzler: Financial Interests, Personal, Invited Speaker, Honoraria: Lilly. F. Marmé: Financial Interests, Personal, Other, Honoraria/expenses: AstraZeneca, GSK/Tesaro, Clovis, MSD, Novartis, Pfizer, Lilly, Roche, Gilead/Immunomedics, Eisai, Celgene, GenicHealth and Myriad Genetics; Financial Interests, Personal, Advisory Board: AstraZeneca, GSK/Tesaro, Clovis, MSD, Novartis, Pfizer, Lilly, Roche, Gilead/Immunomedics, Amgen, Eisai, Celgene, PharmaMar, Janssen-Cilag, GenicHealth, Myriad Genetics and Seagen; Financial Interests, Personal, Research Grant: AstraZeneca, GSK/Tesaro, Clovis, MSD, Novartis, Pfizer, Roche, Gilead/Immunomedics, PharmaMar, GBG and AGO Studiengruppe. E. Pujade-Lauraine: Financial Interests, Personal, Other, Personal fees: AstraZeneca, Tesaro, Clovis, Roche, Incyte, and Pfizer; Non-Financial Interests, Personal, Other: AstraZeneca, Tesaro, and Roche; Financial Interests, Personal, Full or part-time Employment: ARCAGY Research. I.L. Ray-Coquard: Financial Interests, Personal, Other, Honoraria: Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Institutional, Other, Honoraria: GSK, MSD, Roche and BMS; Financial Interests, Personal, Advisory Role: Abbvie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersena, Merck Sereno, Novartis, Amgen, Tesaro and Clovis; Financial Interests, Personal, Research Grant: MSD, Roche and BMS; Financial Interests, Institutional, Research Grant: MSD, Roche, BMS, Novartis, AstraZeneca and Merck Sereno; Financial Interests, Personal, Other, Travel grant: Roche and AstraZeneca and GSK. All other authors have declared no conflicts of interest.