Initia Oncology, Valencia, Spain
Andres Poveda , Stephanie Lheureux , Nicoletta Colombo , David Cibula , Kristina Lindemann , Johanne I Weberpals , Maria Bjurberg , Ana Oaknin , Magdalena Sikorska , Antonio Gonzalez Martin , Radoslaw Madry , María Jesus Rubio , Jonathan A. Ledermann , Richard Davidson , Christopher Blakeley , James Bennett , Jessica Brown , Alan Barnicle , Erik Skof
Background: In the Phase II Study 19 trial (NCT00753545; Ledermann et al Lancet Oncol 2014), maintenance olaparib improved progression-free survival (PFS) vs placebo in PSR OC pts, including non-BRCAm pts. A significant PFS benefit was also seen with maintenance olaparib vs placebo in gBRCAm PSR OC pts in the Phase III SOLO2 trial (NCT01874353; Pujade-Lauraine et alLancet Oncol 2017). To investigate olaparib maintenance monotherapy in non-gBRCAm PSR OC pts who had received ≥2 prior lines of platinum-based chemotherapy (PBC), we performed the Phase IIIb, single-arm, OPINION study (NCT03402841). Methods: Pts had high-grade serous or endometrioid OC and were in complete response (CR) or partial response (PR) to PBC. Pts received maintenance olaparib (tablets; 300 mg bid) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS (modified RECIST v1.1). Secondary endpoints included PFS by homologous recombination deficiency (HRD) and somatic BRCA mutation (sBRCAm) status determined by central Myriad tumor and germline testing; and time to first subsequent treatment (TFST). The primary analysis was planned for 18 months (mo) after the last patient was enrolled. Results: 279 pts were enrolled from 17 countries (mean age: 64 years); 253 pts (90.7%) were confirmed non-gBRCAm. At data cut-off (Oct 2, 2020), median PFS was 9.2 mo (95% CI 7.6–10.9), with 210 PFS events (75.3% maturity). 65.3%, 38.5% and 24.3% of pts were progression-free (PF) at 6, 12 and 18 mo, respectively. The Table shows PFS in key subgroups. Median TFST was 13.9 mo (95% CI 11.5–16.4). Median exposure to olaparib was 9.4 mo (range 0.0–31.9). Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 29.0% of pts and serious TEAEs in 19.7% of pts. TEAEs led to dose interruption, dose reduction and treatment discontinuation in 47.0%, 22.6% and 7.5% of pts, respectively. Conclusions: Our findings support the use of olaparib maintenance therapy in non-gBRCAm PSR OC pts, consistent with our interim analysis and previous trials in this setting. Clinical trial information: NCT03402841
Subgroup | Events, n (%) | Median PFS, mo (95% CI) | PF at 18 mo, % (95% CI) | |
---|---|---|---|---|
Myriad HRD/BRCAm status | HRD+ve* including sBRCAm, n=121 HRD+ve excluding sBRCAm, n=94 sBRCAm, n=27 HRD-ve, n=115 | 80 (66) 67 (71 13 (48) 96 (83) | 11.1 (9.2–14.6) 9.7 (8.1–13.6) 16.4 (12.8–NE) 7.3 (5.5–9.0) | 36.3 (27.6–45.1) 32.5 (23.1–42.3) 49.3 (28.9–66.7) 11.3 (5.9–18.6) |
Prior platinum regimens | 2, n=165 >2, n=114 | 127 (77) 83 (73) | 9.2 (7.4–11.1) 9.0 (7.2–10.9) | 23.7 (17.2–30.7) 25.3 (17.5–33.9) |
Response to last PBC | CR/NED, n=92 PR, n=184 | 60 (65) 147 (80) | 13.7 (9.3–16.4) 7.4 (5.6–9.1) | 36.3 (26.3–46.4) 18.7 (13.2–25.0) |
Enrollment age | <65, n=132 ≥65, n=147 | 100 (76) 110 (75) | 9.2 (7.8–12.8) 9.0 (7.2–10.8) | 26.2 (18.9–34.2) 22.6 (15.9–30.1) |
*Genomic instability score ≥42 NE, not evaluable; NED, no evidence of disease.
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Abstract Disclosures
2020 ASCO Virtual Scientific Program
First Author: Andres Poveda
2022 ASCO Annual Meeting
First Author: Ding Ma
2020 ASCO Virtual Scientific Program
First Author: Andres Poveda
2021 ASCO Annual Meeting
First Author: Cara Amanda Mathews