Improved PFS in Advanced Ovarian Cancer With Senaparib vs Placebo
The phase 3 FLAMES trial results demonstrated an improvement in progression-free survival with senaparib monotherapy vs placebo, regardless of patient subgroup, in patients with newly diagnosed, advanced ovarian cancer.
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Maintenance monotherapy with senaparib (IMP4297) led to reduced risk of disease progression or death vs placebo in patients with newly diagnosed, advanced ovarian cancer. These reductions were observed regardless of the patient's BRCA mutation status, according to results from the phase 3 FLAMES trial (NCT04169997) presented at the 2023 European Society of Medical Oncology (ESMO) Congress.
The median progression-free survival (PFS) by blinded independent central review (BICR) via RECIST 1.1 criteria was not reached (NR) in the senaparib arm compared with 13.6 months in the placebo arm, yielding a 57% risk reduction in progression or death with senaparib (HR, 0.43; 95% CI, 0.32-0.58; P <.0001). At 12 months, the PFS rate in the senaparib arm was 72.2% vs 53.7%, and at 24 months it was 63.0% vs 31.3%.
“The results support senaparib as a maintenance treatment for patients with advanced ovarian cancer after a response to first-line chemotherapy,” Xiaohua Wu, MD, professor in the Department of Gynecology at Fudan University Shanghai Cancer Center, said during the presentation.
A total of 393 patients were enrolled and randomly assigned 1:1 to either the senaparib group (n = 262) at 100 mg each day or the matched placebo group (n = 131). Patients continued treatment for up to 2 years or until disease progression or unacceptable toxicity. The preplanned interim analysis data cutoff date was March 16, 2023, and the median follow-up was 22.3 months.
The primary end point was PFS by BICR, with key secondary end points being PFS by investigator assessment, safety, and time from randomization to discontinuation or death.
Baseline characteristics between the senaparib (n = 271) and placebo (n = 133) groups in the intent-to-treat population included a median age of 55 vs 54. Additionally, a majority had an ECOG performance status of 1 (60.9% vs 57.9%), serous histology (99.8% vs 100%), and a negative BRCA mutation status (65.3 vs 66.9%).
Additional patient characteristics included most having absent gross residual disease after debulking surgery in the senaparib (77.6%) and placebo groups (72.7%), a complete response to platinum-based treatment (87.5% vs 89.5%), and receipt of neoadjuvant chemotherapy (50.6% vs 51.9%). The median cycles of platinum-based treatment were 7 in both arms.
Treatment discontinuation occurred in 72.7% of patients in the senaparib arm vs 87.2% in the placebo group. Reasons for discontinuation included disease progression (30.6% vs 60.9%), completing 2 years of treatment (25.1% vs 16.5%), patient or investigator decision (12.5% vs 9.8%), or adverse effects (AEs; 4.4% vs 0.0%) between both groups, respectively. At the data cutoff, 27.3% of patients in the senaparib arm and 12.8% in the placebo arm were still receiving treatment. In the senaparib arm, the median duration of study treatment was 18.7 months vs 11.4 months in the placebo arm.
For patients who were BRCA mutation-positive, the median PFS was NR in the senaparib arm vs 15.6 months in the placebo arm (HR, 0.43; 95% CI, 0.24-0.76; P = .0026). For those with BRCA-negative disease, the median PFS was NR in the senaparib arm and 12.9 months in the placebo arm (HR, 0.43; 95% CI, 0.30-0.61; P <.0001).
All secondary end points showed the superiority of senaparib. The end points included median PFS by investigator assessment (HR, 0.43; 95% CI, 0.32-0.57; P <.0001), median time from randomization to discontinuation or death (HR, 0.68; 95% CI, 0.54-0.86; P = .0003), chemotherapy-free interval (HR, 0.41; 95% CI, 0.30-0.55; P <.0001), and median time from randomization to first subsequent therapy or death (HR, 0.44; 95% CI, 0.33-0.59; P <.0001).
AEs of grade 3 or higher occurred in 66.3% of patients in the senaparib arm vs 20.3% in the placebo arm, with treatment-emergent AEs (TEAEs) being reported in 99.6% vs 97.7%, and serious AEs in 27.8% vs 3.8%. As a result of TEAEs, dose interruptions occurred in 76.7% vs 19.5%, dose reductions in 63.3% vs 6.0%, and discontinuation in 4.4% vs 0.0% in the senaparib and placebo arms, respectively.
In the senaparib arm, the most common TEAEs of grade 3 or higher were anemia (n = 29), thrombocytopenia (n = 27), and neutropenia (n = 25). In the placebo arm, the most common were hypertriglyceridemia (n = 4); weight increase (n = 3); and neutropenia, leukopenia, and abdominal pain occurring in 2 patients each.
“Senaparib demonstrated a tolerable safety profile with a very low incidence of permanent discontinuation and no significant safety concerns observed,” Wu concluded.
