Findings from a subgroup analysis of the phase III PAOLA-1/ENGOT-ov25 study presented at the ESMO Asia Virtual Congress 2020, held from 20 to 22 November 2020, show that the addition of olaparib to bevacizumab maintenance following standard platinum-based therapy plus bevacizumab provided a progression-free survival (PFS) benefit over bevacizumab alone in the Japan subset of patients with advanced ovarian cancer.
Professor Keiichi Fujiwara of the Gynaecologic Oncology Department at the Saitama Medical University International Medical Centre in Saitama, Japan presented data from the Japanese subset of patients participating in the international phase III PAOLA-1/ENGOT-ov25 study (NCT02477644).
Previously reported findings from this study demonstrated that patients with newly diagnosed advanced ovarian cancer receiving maintenance olaparib in addition to standard first-line platinum-based chemotherapy plus bevacizumab had a statistically significant PFS benefit (hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.49–0.72).1
The PAOLA-1/ENGOT-ov25 study enrolled patients with newly diagnosed, FIGO (International Federation of Gynecology and Obstetrics) stage III–IV, high-grade serous or endometrioid ovarian cancer, fallopian tube, or primary peritoneal cancer who had no evidence of disease or were in clinical complete or partial response following first-line treatment with platinum-based chemotherapy plus bevacizumab.
Folllowing 2:1 randomisation, where patients were stratified by first-line treatment outcome and tumour BRCA mutation status, in the Japan subset 15 patients received oral olaparib tablets at 300 mg twice daily for up to 24 months plus bevacizumab at 15 mg/kg on day one every 3 weeks for up to 15 months and nine patients received bevacizumab alone.
Patient characteristics were generally well balanced; 20% of patients in the olaparib/bevacizumab arm and 22% of patients in the bevacizumab-alonearm had a tumour BRCA mutation and 67% of patients in each arm had homologous recombination deficiency (HRD)-positive status.
The primary endpoint was investigator-assessed PFS per modified RECIST v1.1.
PFS was prolonged with the addition of olaparib according to both investigator and BICR assessment
With a median follow-up time of 27.7 months in the olaparib/bevacizumab arm and 24.0 months in the bevacizumab alone arm, median PFS per investigator assessment was 27.4 months (95% CI 11.1–not reached) versus 19.4 months (95% CI 3.1–24.0) in the respective treatment arms (HR, 0.34; 95% CI, 0.11–1.00). Median PFS according to blinded independent central review (BICR) was 27.2 months versus 18.3 months, respectively (HR 0.40; 95% CI 0.13–1.23).
By investigator assessment PFS events occurred in 53% of patients receiving olaparib/bevacizumab versus 89% of patients receiving bevacizumab alone and according to BICR, PFS events occurred in 47% versus 78% of patients, respectively.
Adverse events (AEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥3 (version 4.03) were reported by 73% of patients receiving olaparib/bevacizumab compared with 33% of patients receiving bevacizumab alone. The most commonly reported of these were anaemia in five and leukopenia in four patients treated with olaparib/bevacizumab. No cases of myelodysplastic syndrome, acute myeloid leukaemia or new primary malignancies were observed.
Dose interruptions due to an AE occurred in 73% of patients receiving olaparib/bevacizumab versus 44% of patients receiving bevacizumab alone, and discontinuations were reported for 27% versus 11% of patients in the respective groups. Sixty percent of patients treated with olaparib/bevacizumab had dose reductions.
The authors found that patients in the Japan subset of PAOLA-1, demonstrated efficacy results that were generally consistent with those in the overall population, but that the proportion of patients experiencing a Grade ≥3 AEwas generally higher in the subset than in the overall population.
They noted that the subgroup analysis was limited by the small number of patients.
This study was funded by ARCAGY Research, AstraZeneca, Merck & Co., and F. Hoffmann-La Roche.
- Ray-Coquard I, et al. N Engl J Med 2019;381:2416-2428. DOI: 10.1056/NEJMoa1911361.
236O – Fujiwara K, Fujiwara H, Yoshida H, et al. Olaparib (ola) plus bevacizumab (bev) as maintenance (mx) therapy in patients (pts) with newly diagnosed advanced ovarian carcinoma (OC): Japan subset of the PAOLA-1 trial. ESMO Asia Virtual Congress 2020 (20-22 November).