Niraparib PFS benefit in ovarian cancer consistent regardless of time to progression, response to prior chemo
Niraparib maintenance therapy improved progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PSROC) regardless of time to progression since penultimate platinum chemotherapy or response to last chemotherapy, according to subgroup analyses of the NORA trial.
The phase III, double-blind trial included 265 patients with PSROC who had completed ≥2 lines of platinum-based chemotherapy and had a complete (CR) or partial response (PR) to the last platinum chemotherapy. They were randomized 2:1 to receive oral niraparib (200 or 300 mg QD based on body weight or platelet count) or placebo.
Of these, 84 progressed 6–12 months post-penultimate platinum chemo (56 and 28 niraparib and placebo recipients, respectively) and 181 progressed >12 months post-platinum chemo (121 and 60, respectively).
Among patients who experienced disease progression 6–12 months after penultimate chemotherapy, niraparib maintenance therapy significantly extended PFS vs placebo (median 11.17 vs 3.71 months; hazard ratio [HR], 0.31, 95 percent confidence interval [CI], 0.17–0.55; p<0.0001). [SGO 2021, abstract 10898]
PFS was similarly extended with niraparib vs placebo in patients who experienced disease progression >12 months after penultimate chemotherapy (median 18.36 vs 5.52 months; HR, 0.33, 95 percent CI, 0.22–0.51; p<0.0001).
This PFS benefit with niraparib vs placebo was consistent regardless of germline (g)BRCA mutation status (gBRCA: median 18.33 vs 3.73 months; HR, 0.16; p=0.0004 [6–12 months] and median not reached vs 5.52 months; HR, 0.26; p<0.0001 [≥12 months]; non-gBRCA: median 11.07 vs 3.71 months; HR, 0.41; p=0.0078 [6–12 months] and median 10.41 vs 5.49 months; HR, 0.40; p=0.0013 [≥12 months]).
Treatment-emergent adverse events (TEAEs) led to dose reduction in 62.5 percent of niraparib and 10.7 percent of placebo recipients who experienced disease progression at 6–12 months and 58.7 and 15.0 percent of those who progressed at ≥12 months. TEAE-related discontinuations occurred in two niraparib and no placebo recipients among those who progressed at 6–12 months, and in five patients in each group among those who progressed at ≥12 months.
The most common grade ≥3 TEAEs in niraparib recipients were decreased neutrophil count (32.1 and 14.9 percent of those who progressed at 6–12 and ≥12 months, respectively), anaemia (17.9 and 13.2 percent), decreased platelet count (14.3 and 9.9 percent), and decreased white blood cell count (10.7 and 5.8 percent).
“Niraparib maintenance treatment provides a similar PFS benefit vs placebo in patients with a time-to-progression after penultimate platinum-based chemotherapy of 6–12 or ≥12 months, regardless of gBRCA mutation status,” noted the authors.
PFS benefit consistent regardless of prior response to chemo
In another NORA subgroup analysis, the PFS benefit of niraparib was consistent in patients with CR or PR to their last platinum-based chemotherapy regimen.
About half the patient population (50.2 percent; n=133) experienced CR to last platinum-based chemotherapy (86 and 47 niraparib and placebo recipients, respectively), while 49.4 percent (n=131) experienced PR (90 and 41, respectively).
PFS was significantly longer with niraparib vs placebo in patients with CR (median not reached vs 5.75 months; HR, 0.26, 95 percent CI, 0.15–0.45) and PR to last chemotherapy (median 8.54 vs 3.68 months; HR, 0.33, 95 percent CI, 0.21–0.52; p<0.0001 for both). [SGO 2021, abstract 10901]
This PFS benefit was consistent regardless of gBRCA mutation status (gBRCA: median not reached vs 5.49 months; HR, 0.12; p<0.0001 [CR] and median 10.97 vs 3.76 months; HR, 0.36; p=0.0092 [PR]; non-gBRCA: median 18.46 vs 7.43 months; HR, 0.45; p=0.0177 [CR] and median 7.43 vs 3.68 months; HR, 0.34; p<0.0001 [PR]).
TEAEs led to dose reduction in 55.8 and 17.0 percent of niraparib and placebo recipients, respectively, with previous CR, and in 63.3 and 9.8 percent, respectively, with previous PR. TEAE-related discontinuations occurred in 4.7 and 3.3 percent of niraparib recipients who achieved CR and PR, respectively, and in 4.3 and 7.3 percent of placebo recipients who achieved CR and PR, respectively.
The most common (≥5 percent) grade ≥3 TEAEs in niraparib recipients were decreased neutrophil, white blood cell, and platelet counts, and anaemia.
“Compared with placebo, niraparib maintenance therapy reduced the risk of disease progression in patients with PSROC achieving a CR or PR to the last platinum-based therapy, regardless of gBRCA mutation status,” the authors concluded.