51P Efficacy and safety by time to maintenance therapy treatment initiation in PRIMA/ENGOT-OV26/GOG-3012

To help delay cancer recurrence, maintenance treatment (MT) with PARP inhibitors is recommended in patients (pts) with advanced ovarian cancer (OC) that responded to 1L platinum-based chemotherapy (PBCT). Because PARP inhibitors, including niraparib, are associated with early hematologic adverse events, understanding when to initiate MT after 1L PBCT to best optimize safety and efficacy is vital. In the phase 3 PRIMA study, eligible pts had newly diagnosed advanced epithelial OC that responded to 1L PBCT. Pts were randomized 2:1 to receive either niraparib (nir) or placebo (PBO) MT within 12 wks after completion of the last dose of 1L PBCT. This post hoc analysis grouped pts by time from end of 1L PBCT to randomization (<8 vs ≥8 wks) and evaluated investigator-assessed progression-free survival (PFS) and safety outcomes (17 Nov 2021 clinical cutoff date; median follow-up, 3.5 years). Overall, 356 pts (nir, 236; PBO, 120) were randomized <8 wks after 1L PBCT and 377 pts (nir, 251; PBO, 126) were randomized ≥8 wks after 1L PBCT. Median time from the end of 1L PBCT to randomization (range): <8 wks subgroup, nir, 6.1 wks (0.3–7.9 wks) and PBO, 5.7 wks (1.1–7.9 wks); ≥8 wks subgroup, nir, 10.6 wks (8.0–28.0 wks) and PBO, 10.8 wks (8.0–26.14 wks). The PFS benefit of nir was similar in pts randomized <8 wks and ≥8 wks after the end of 1L PBCT (Table). The percentages of pts who experienced any-grade treatment-emergent adverse events (TEAEs) were similar across subgroups in both treatment arms (Table). In the nir arm, the percentages of pts who experienced TEAEs leading to dose interruptions and reductions were slightly higher in pts randomized <8 wks than in pts randomized ≥8 wks after the end 1L PBCT.Table: 51PTime from end of 1L PBCT to randomization<8 wks≥8 wksNirPBONirPBOPFSan=236n=120n=251n=126Median PFS, mo13.88.213.98.4Hazard ratio (95% CI)0.64 (0.50–0.83)0.67 (0.52–0.86)TEAE, n (%)bn=236n=119n=248n=125Any-grade233 (98.7)109 (91.6)246 (99.2)120 (96.0)Leading to dose interruption197 (83.5)22 (18.5)192 (77.4)29 (23.2)Leading to dose reduction177 (75.0)8 (6.7)170 (68.5)15 (12.0)Leading to treatment discontinuation31 (13.1)2 (1.7)36 (14.5)5 (4.0)aEfficacy evaluable pts. bSafety evaluable pts. 1L, first-line; nir, niraparib; PBCT, platinum-based chemotherapy; PBO, placebo; PFS, progression-free survival; pts, patients; TEAE, treatment-emergent adverse event. Open table in a new tab aEfficacy evaluable pts. bSafety evaluable pts. 1L, first-line; nir, niraparib; PBCT, platinum-based chemotherapy; PBO, placebo; PFS, progression-free survival; pts, patients; TEAE, treatment-emergent adverse event. Within the allowable 12-wk interval, efficacy and safety outcomes were generally similar regardless of time to MT initiation in PRIMA. Pt safety should be considered when beginning nir MT soon after 1L PBCT to allow for recovery from chemotherapy-induced myelosuppression.