Maintenance Olaparib/Bevacizumab Provides Substantial PFS, PFS2 Benefit in HRD+ Ovarian Cancer, Irrespective of Disease Stage

The addition of olaparib (Lynparza) to bevacizumab (Avastin) provided a substantial progression-free survival (PFS) and second PFS (PFS2) benefit over bevacizumab alone in the maintenance treatment of patients with homologous recombination deficiency (HRD)–positive, newly diagnosed advanced ovarian cancer, regardless of International Federation of Gynecology and Obstetrics (FIGO) disease stage, according to data from an exploratory analysis of the phase 3 PAOLA-1/ENGOT-ov25 trial (NCT02477644).¹

Results, which were presented in a poster session during the 2021 ASCO Annual Meeting, showed that at a median follow-up of 24.8 months, the median PFS was 39.3 months (95% CI, 36.0–not evaluable [NE]) with olaparib/bevacizumab in patients with HRD-positive tumors and stage III disease vs 19.9 months (95% CI, 17.7-23.4) with bevacizumab alone (HR, 0.32; 95% CI, 0.22-0.47).

In patients with HRD-positive tumors and stage IV disease, the median PFS with the combination was 25.1 months (95% CI, 22.0-37.2) vs 12.8 months (95% CI, 10.4-15.8) with bevacizumab alone (HR, 0.32; 95% CI, 0.20-0.52).

Moreover, in patients with lower risk disease, defined as those with stage III disease who did not have residual disease following up-front surgery, the median PFS2 was not reached with the doublet vs 44.3 months (95% CI, 37.9–NE) with bevacizumab alone.

In those with higher risk disease, defined as those with stage III disease who have residual disease following up-front surgery or who received neoadjuvant chemotherapy or those who have stage IV disease, the median PFS2 with the combination was 50.3 months (95% CI, 34.6-50.3) vs 32.6 months (95% CI, 25.7-42.2) with bevacizumab alone (HR, 0.66; 95% CI, 0.47-0.93).

“Remarkably, the 2- and 3-year PFS2 rates were greater than 90% with maintenance olaparib plus bevacizumab in lower risk patients with HRD-positive tumors who benefitted from complete resection during up-front surgery,” Patricia Pautier, MD, lead study author and head of the Medical Day Hospital Unit at the Institut Gustave Roussy Cancer Campus, said during a poster presentation on the data.

In the PAOLA-1/ENGOT-ov25 study, the addition of olaparib to bevacizumab in the first-line maintenance treatment of patients with HRD-positive, advanced high-​grade ovarian cancer resulted in a significant improvement in PFS. The benefit was most pronounced in those with HRD positivity, including those with BRCA mutations (HR, 0.33; 95% CI, 0.25-0.45). In this subgroup of patients, the median PFS was 37.2 months and 17.7 months in the investigative and control arms, respectively. In those with HRD-positive tumors without BRCA mutations, the median PFS was 28.1 months and 16.6 months in the investigative and control arms, respectively (HR, 0.43; 95% CI, 0.28-0.66).²

These data supported the May 2020 FDA approval of olaparib plus bevacizumab for maintenance treatment; the regimen has also been approved in other countries like Europe and Japan. In the analysis presented during the meeting, investigators sought to explore the efficacy of the regimen in patients with HRD-positive tumors by FIGO disease stage and surgical outcome.

Patients enrolled to the study had newly diagnosed, FIGO stage III to stage IV high-grade serous or endometroid ovarian, fallopian tube, and/or peritoneal cancer. Patients received first-line treatment with up-front or interval surgery, platinum/taxane-based chemotherapy, and 2 or more cycles of bevacizumab.

Study participants were randomized 2:1 to receive either olaparib at 300 mg twice daily for 2 years plus bevacizumab, or placebo plus bevacizumab. Patients were stratified based on BRCA mutational status and first-line treatment outcome. Of the 806 patients who were randomized on study, 48% (n = 387) had HRD-positive status; 70% (n = 272) had stage III disease, and 30% (n = 115) had stage IV disease.

Age, BRCA mutational status, and surgical status were found to be well balanced between the treatment arms within each subgroup. However, a higher proportion of patients with stage IV disease had residual disease following surgery in the bevacizumab-alone arm vs the combination arm, at 38.9% and 29.7%, respectively.

Additional data showed that in those with HRD positivity and stage III disease, The 2-year PFS rate with olaparib/bevacizumab was 72% vs 36% with bevacizumab alone. In those with HRD positivity and stage IV disease, the 2-year PFS rates in the investigative and control arms were 52% and 17%, respectively.

When looking at patients with lower risk disease, the PFS2 rates at 2 years in the investigative and control arms were 94.7% vs 90.6%, respectively; at 3 years, these rates were 91.9% vs 65.7%, respectively. In patients with higher risk disease, the 2-year PFS2 rates in the investigative and control arms were 73.9% and 69.1%, respectively; the 3-year PFS2 rates were 57.1% and 42.3%, respectively.

References

1. Pautier P, Harter P, Pisano C, et al. Progression-free survival (PFS) and second PFS (PFS2) by disease stage in patients (pts) with homologous recombination deficiency (HRD)-positive newly diagnosed advanced ovarian cancer receiving bevacizumab (bev) with olaparib/placebo maintenance in the phase III PAOLA-1/ENGOT-ov25 trial. J Clin Oncol. 2021;39(suppl 15)5514. doi:10.1200/JCO.2021.39.15_suppl.5514
2. Ray-Coquard I, Pautier P, Pignata S, et al. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361