Abstract 740P
Background
Maintenance olaparib is a standard of care for PSR OC patients (pts), including those without a BRCA1 and/or BRCA2 mutation (BRCAm). The OPINION (NCT03402841) primary analysis showed clinical benefit with maintenance olaparib monotherapy in non-gBRCAm pts, and by homologous recombination deficiency (HRD) genomic instability status, compared with historical placebo controls (Poveda et al. ASCO 2021). Here, we assessed exploratory biomarkers beyond HRD that may be predictive of response in non-gBRCAm PSR OC.
Methods
279 pts were enrolled and received olaparib maintenance (tablets; 300 mg bid). Tumour tissue samples were analysed by Myriad MyChoice HRD Plus assay to determine homologous recombination repair gene mutation (non-BRCA HRRm; qualifying alteration detected in at least 1 of 13 prespecified HRR genes, excluding BRCAm) and TP53 mutation status. TP53 mutations were classified as disruptive (D) or non-disruptive (ND) relative to the degree of p53 protein function and structure disturbance, and wild type (WT) if no TP53 mutation was observed. Progression-free survival (PFS) by subgroup was investigator-assessed (modified RECIST v1.1).
Results
12% of pts (34/279) had a non-BRCA HRRm (8 RAD51C; 7 BRIP1; 7 RAD51D; 3 CDK12; 2 FANCL; 2 PALB2; 1 ATM; 1 BARD1; 1 RAD51B; 1 CHEK2 and RAD51D; 1 PPP2R2A and RAD51C). At data cut-off (2 Oct 2020), median PFS was 14.8 and 7.6 months (mo) for non-BRCA HRRm and non-HRRm subgroups, respectively. In the TP53(D), TP53(ND) and TP53(WT) subgroups, median PFS was 8.1, 10.8 and 10.7 mo, respectively (Table). Table: 740P
| Subgroup | Pts, n | PFS events, n (%) | Median PFS, mo (95% CI) | PF at 12 mo,% (95% CI) | PF at 18 mo,% (95% CI) | |
| Full analysis set | 279 | 210 (75) | 9.2 (7.6–10.9) | 38.5 (32.7–44.3) | 24.3 (19.2–29.7) | |
| Non-BRCA HRRm status | HRRm Non HRRm | 34 198 | 18 (53) 163 (82) | 14.8 (10.8–NE) 7.6 (7.2–9.1) | 60.1 (41.3–74.6) 29.7 (23.3–36.3) | 43.5 (25.9–59.8) 17.5 (12.4–23.5) |
| TP53 mutation status | D ND WT | 131 117 19 | 103 (79) 82 (70) 14 (74) | 8.1 (7.2–10.3) 10.8 (8.1–13.7) 10.7 (7.2–13.6) | 34.9 (26.7–43.3) 43.4 (34.1–52.3) 42.1 (20.4–62.5) | 19.0 (12.5–26.6) 31.0 (22.5–39.8) 24.1 (7.8–45.1) |
CI, confidence interval; NE, not evaluable; PF, progression-free.
.Conclusions
Despite limitations in subgroup size, clinical benefit with maintenance olaparib was observed in non-gBRCAm pts with PSR OC, irrespective of biomarker status. Pts with a non-BRCA HRRm achieved longer PFS benefit compared with the non HRRm subgroup. TP53 mutation status was not predictive of olaparib sensitivity in this setting.
Clinical trial identification
NCT03402841.
Editorial acknowledgement
Medical writing assistance was provided by Rachel Dodd, 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
AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
K. Lindemann: Financial Interests, Personal, Advisory Role, Consulting/advidory: AstraZeneca, GSK and Esai; Financial Interests, Personal, Research Grant: GSK. N. Colombo: Financial Interests, Personal, Advisory Role, Advisory/consulting: Roche, Pharmamar, AstraZeneca, MSD/Merk, Clovis Oncology, Tesaro, GSK, Novartis, Pfizer, Takeda, BIOCAD, Immunogen, Mersana, Eisai, Oncxerna. A. González-Martín: Financial Interests, Personal, Research Grant, Funding for ENGOT Ov41 trial /ANITA: ROCHE & GSK; Financial Interests, Personal, Advisory Role, Consulting: Alkermes, Amgen, AstraZeneca, Clovis, GSK, Genmab, Mersana, Roche, MSD, Inmunogen, Oncoinvent, Pharmamar, Sotio, Takeda; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Clovis, GSK, Roche, MSD; Financial Interests, Personal, Other, Travel grant: AstraZeneca, GSK, Roche, MSD, Pharmamar; Financial Interests, Personal, Leadership Role, Chairman: GEICO; Financial Interests, Personal, Leadership Role, Chairman (2018-2020): ENGOT. R. Davidson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. C. Blakeley: Financial Interests, Personal, Full or part-time Employment, Recently retired: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Bennett: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Barnicle: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Poveda: Financial Interests, Personal, Advisory Role, Consulting/advisory roles: AstraZeneca, Clovis Oncology, GlaxoSmithKline, Roche, Tesaro. All other authors have declared no conflicts of interest.