Abstract 531P
Background
The Phase IIIb, single-arm OPINION study reported a median progression-free survival (PFS) of 9.2 months (mo) with maintenance olaparib in pts with non-gBRCAm PSR OC (Poveda et al. Gynecol Oncol 2022). Here, we report final OS and updated safety data.
Methods
Pts with non-gBRCAm PSR OC and ≥2 prior lines of platinum-based chemotherapy (PBC) in complete or partial response to their last PBC received maintenance olaparib (300 mg bid) until progression/unacceptable toxicity. OS was a secondary endpoint. Ad hoc subgroup analyses included OS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status according to central Myriad tumor and germline testing.
Results
In total, 279 pts were enrolled and received olaparib (median [range] age: 65 [40–85] years); 253 (90.7%) pts were retrospectively confirmed as non-gBRCAm. At data cutoff (Sep 17, 2021), 46 (16.5%) pts remained on therapy; discontinuation was mainly due to disease progression (n=196; 70.3%). Overall, there were 146 deaths (52.3% maturity); median follow-up in censored pts was 33.1 mo. Median OS was 32.7 (95% confidence interval [CI], 29.5–35.3) mo; 24- and 30-mo Kaplan–Meier OS rates were 65.8% and 54.9%, respectively. OS by HRD status and platinum sensitivity is in the Table. With a median total duration of therapy of 9.6 mo, grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 82 (29.4%) pts, and serious TEAEs in 58 (20.8%). TEAEs led to dose interruption and reduction in 139 (49.8%) and 65 (23.3%) pts, respectively; TEAEs led to olaparib discontinuation in 23 (8.2%) pts. In total, two cases of myelodysplastic syndrome were reported, with no new cases since the primary analysis. There were no new safety findings. Table: 531P
OS in key subgroups in OPINION
| Subgroup | Events, n/N (%) | 30-mo Kaplan–Meier OS rate, % (95% CI) | |
| HRD and sBRCAm status | HRD positive* including sBRCAm | 50/121 (41.3) | 66.7 (57.5–74.3) |
| HRD positive* excluding sBRCAm | 41/94 (43.6) | 65.6 (55.0–74.3) | |
| sBRCAm | 9/27 (33.3) | 70.4 (49.4–83.9) | |
| HRD negative | 77/115 (67.0) | 38.9 (29.9–47.8) | |
| Platinum sensitivity | Partial (6–12 mo) † | 55/88 (62.5) | 40.2 (29.9–50.3) |
| Full (≥12 mo) † | 87/185 (47.0) | 62.6 (55.1–69.2) |
*Genomic instability score ≥42; †PFS from last dose of penultimate PBC
Conclusions
OS and updated safety data from OPINION further support the use of maintenance olaparib in pts with non-gBRCAm PSR OC.
Clinical trial identification
NCT03402841.
Editorial acknowledgement
Medical writing assistance was provided by Adam Gill, MRes, at Cence, and was funded by AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
Disclosure
A.M. Poveda Velasco: Financial Interests, Personal, Advisory Board: Roche, Tesaro/GSK, PharmaMar, Clovis, MSD, AstraZeneca, GSK; Financial Interests, Personal, Invited Speaker: AstraZeneca. S. Lheureux: Financial Interests, Personal, Advisory Role: AstraZeneca, Eisai, GlaxoSmithKline, Merck, Novocure; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eisai, GlaxoSmithKline; Financial Interests, Institutional, Funding: AstraZeneca,GlaxoSmithKline, Merck, Regeneron, Repare, Roche. N. Colombo: Financial Interests, Personal, Advisory Board, Various: Roche, PharmaMar, AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GSK, Pfizer, Takeda, BIOCAD, ImmunoGen, Mersana; Financial Interests, Personal, Invited Speaker, Congress, Symposia, Lectures: AstraZeneca, Tesaro; Financial Interests, Personal, Invited Speaker, Lectures: Novartis; Financial Interests, Personal, Advisory Board, Lectures: Eisai; Financial Interests, Personal, Advisory Board, Advisory role: Nuvation Bio, Pieris; Financial Interests, Personal, Advisory Board, Advisory Role: Onxerna; Financial Interests, Institutional, Research Grant: AstraZeneca, PharmaMar, Roche; Non-Financial Interests, Other, Sterring committee member Clinical Guidelines: ESMO; Non-Financial Interests, Leadership Role, Chair, Scientific Committee: ACTO( Alleanza contro il tumore ovarico). D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Sotio, Novocure, MSD, GSK, Akesobio, Seagen; Financial Interests, Personal, Invited Speaker: AstraZeneca. J. Weberpals: Financial Interests, Personal, Funding: AstraZeneca. A.J. Gonzalez Martin: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Clovis, GSK, Genmab, Alkermes, Sutro, Roche, Sotio, PharmaMar, Oncoinvent, Novartis, Mersana, MSD, Macrogenics; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis, Roche, Novocure, MSD; Financial Interests, Institutional, Invited Speaker, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Invited Speaker, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Invited Speaker, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Invited Speaker, ENGOT PI of AVB-500 phase III trial: ARAVIVE. R. Madry: Financial Interests, Personal, Advisory Role: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GlaxoSmithKline, Roche; Financial Interests, Personal, Other, Travel: AstraZeneca, Roche; Other, Institutional, Other, Receipt of materials or services: AstraZeneca, Roche. J.A. Ledermann: Financial Interests, Personal, Funding: AstraZeneca and Merck/ MSD; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline, MSD, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis Oncology, Eisai, GlaxoSmithKline,MSD, Pfizer, Regeneron; Financial Interests, Personal, Leadership Role: ESGO (Vice President), ESMO (Editor, Gynaecological Clinical Practice Guidelines). O. Ozgoren: 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. H. Marshall: Financial Interests, Personal, Advisory Role: AstraZeneca. Z. Bashir: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. All other authors have declared no conflicts of interest.