Findings from a subgroup analysis of the phase III PAOLA-1/ENGOT-ov25 study presented by Fujiwara et al at the ESMO Asia Virtual Congress 2020 showed that the addition of olaparib to bevacizumab maintenance following standard platinum-based therapy plus bevacizumab provided a progression-free survival benefit over bevacizumab alone in a Japanese subset of patients with advanced ovarian cancer (Abstract 236O).
Previously reported findings from this study (by Ray-Coquard et al in The New England Journal of Medicine) 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 progression-free survival benefit (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.49–0.72).
Trial Details
The PAOLA-1/ENGOT-ov25 study enrolled patients with newly diagnosed, FIGO (International Federation of Gynecology and Obstetrics) stage III or IV, high-grade serous or endometrioid ovarian, 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.
Following 2:1 random assignment—where patients were stratified by first-line treatment outcome and tumor BRCA mutation status—in the Japanese 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 1 every 3 weeks for up to 15 months, and 9 patients received bevacizumab alone.
Twenty percent of patients in the olaparib/bevacizumab arm and 22% of patients in the bevacizumab-alone arm had a tumor BRCA mutation; 67% of patients in each arm had homologous recombination deficiency (HRD)-positive status.
The primary endpoint was investigator-assessed progression-free survival per modified Response Evaluation Criteria in Solid Tumors version 1.1.
Results
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 progression-free survival per investigator assessment was 27.4 months (95% confidence interval [CI] = 11.1–not reached) vs 19.4 months (95% CI = 3.1–24.0) in the respective treatment arms (hazard ratio [HR] = 0.34, 95% CI = 0.11–1.00). Median progression-free survival according to blinded independent central review was 27.2 months vs 18.3 months, respectively (HR = 0.40, 95% CI = 0.13–1.23).
By investigator assessment, progression-free survival events occurred in 53% of patients receiving olaparib/bevacizumab vs 89% of patients receiving bevacizumab alone. According to blinded independent central review, progression-free survival events occurred in 47% vs 78% of patients, respectively.
Grade ≥ 3 adverse events were reported by 73% of patients receiving olaparib/bevacizumab compared with 33% of patients receiving bevacizumab alone. The most commonly reported of these were anemia in five and leukopenia in four patients treated with olaparib/bevacizumab. No cases of myelodysplastic syndrome, acute myeloid leukemia, or new primary malignancies were observed.
Dose interruptions due to an adverse event occurred in 73% of patients receiving olaparib/bevacizumab vs 44% of patients receiving bevacizumab alone, and discontinuations were reported for 27% vs 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 Japanese 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 adverse event was generally higher in the subset than in the overall population. They noted that the subgroup analysis was limited by the small number of patients.
Disclosure: This study was funded by ARCAGY Research, AstraZeneca, Merck & Co, and F. Hoffmann-La Roche. For full disclosures of the study authors, visit oncologypro.esmo.org.
