Evidence for maintenance treatment with PARP inhibitors as the standard of care in the frontline setting for patients with ovarian cancer continues to mount, according to additional analyses from the phase 3 PRIMA trial and the phase 3 PAOLA-1 trial released as part of the virtual platform for the Society of Gynecologic Oncology (SGO) 2020 Annual Meeting on Women’s Cancer.
BRCA and HRD status in the PRIMA Trial
As its primary end point, the phase 3 PRIMA trial demonstrated that frontline maintenance with niraparib (Zejula) improved median progression-free survival (PFS) by 5.6 months compared with placebo (13.8 vs 8.2 months; HR for disease progression or death, 0.62; 95% CI, 0.50-0.76; P <.001).1
As part of that analysis, investigators looked at homologous recombination deficiency (HRD) and BRCA status as key biomarkers of PFS. Of the 733 randomized patients, 373 (51%) had tumors with HRD, while 249 (34%) of patients had homologous recombination–proficient tumors.2
The HR for PFS in the HRD cohort was 0.43 (95% CI, 0.310-0.588; P <.0001), while the HR in the homologous recombination–proficient group was 0.68 (95% CI, 0.492-0.944; P = .0203). In patients with BRCA mutations, the HR for PFS was 0.40 (95% CI, 0.265-0.618; P <.0001), while the HR was 0.50 (95% CI, 0.305-0.831; P = .0064) in the BRCA wild-type patient population.
PFS2 and TFST as Secondary End Points
Also reported through the SGO virtual platform was an analysis of time to first subsequent therapy (TFST) and time to second objective disease progression (PFS2). In the overall population, an increase of 6.6 months in median TFST was shown for patients receiving niraparib versus placebo (HR, 0.65; 95% CI, 0.52-0.80; P = .0001).3
In the patients with HRD tumors, median TFST had not yet been reached for patients receiving niraparib, compared with 13.7 months in patients receiving placebo (HR, 0.64; 95% CI, 0.46-0.90; P <.0105). Data maturity for TFST in the overall population was at 47%.
With the available results for PFS2 at 20% data maturity, HR in the overall (0.81; 95% CI, 0.58-1.14), HRD (HR, 0.84; 95% CI, 0.49-1.45), and homologous recombination–proficient (HR, 0.56; 95% CI, 0.34-0.91) populations all favored the niraparib arm.
Olaparib Plus Bevacizumab Leads to Improved Outcomes
Results from the phase 3 PAOLA-1 trial showed that the combination of olaparib (Lynparza) plus bevacizumab (Avastin) led to improved PFS versus treatment with bevacizumab alone as frontline maintenance in patients with newly diagnosed high-grade serous ovarian cancer, regardless of residual disease status or timing of surgery.
Previously published results of the trial found an overall improvement in median PFS of 5.5 months (22.1 vs 16.6 months; HR for disease progression or death, 0.59; 95% CI, 0.49-0.72; P <.001).4
New data, which were released through the 2020 SGO Annual Meeting on Women’s Cancer digital platform, stratified the 537 patients by residual disease status and timing of surgery and showed the benefit of olaparib plus bevacizumab across all cohorts.
The regimen demonstrated the most significant improvement in patients who had upfront surgery with no residual disease, leading to an increase in median PFS of 17.2 months (39.3 vs 22.1 months; HR, 0.47; 95% CI, 0.29-0.75; P <.001) for those in the olaparib plus bevacizumab arm.5
Among all those who underwent upfront surgery, the investigative regimen led to a median PFS of 29.6 months (HR, 0.52; 95% CI, 0.40-0.69) versus 18.2 months in the control arm, while patients who underwent interval surgery had a median PFS increase of 10.3 months (29.6 vs 19.3 months; HR, 0.54; 95% CI, 0.42-0.71).
1. González-Martin A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962
2. Monk BJ, Gonzalez-Martin A. Efficacy of niraparib therapy in patients with newly diagnosed advanced ovarian cancer by BRCA and homologous recombination status: PRIMA/ENGOT-OV26/GOG-3012 study. Data made available as part of the virtual platform for the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer. Abstract 31.
3. Han SN, Monk BJ, Gonzalez-Martin A. Time to first subsequent therapy (TFST) and progression-free survival 2 (PFS2) from the phase 3 randomized, double-blind PRIMA/ENGOT-OV26/GOG-3012 study in patients with newly diagnosed ovarian cancer. Data made available as part of the virtual platform for the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer. Abstract 32.
4. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus bevacizumab as first-line maintenance in ovarian cancer. N Engl J Med. 2019;381(25):2416-2428. doi:10.1056/NEJMoa1911361
5. Grimm C, Cropet C, Ray-Coquard I. Maintenance olaparib plus bevacizumab (bev) after platinum-based chemotherapy plus bev in patients (pts) with newly diagnosed advanced high-grade ovarian cancer (HGOC): efficacy by timing of surgery and residual tumor status in the phase III PAOLA-1 trial. Data made available as part of the virtual platform for the Society of Gynecologic Oncology 2020 Annual Meeting on Women’s Cancer. Abstract 34.