Rational adjustment of dose to reduce adverse reactions (RADAR) in patients with platinum-sensitive recurrent ovarian cancer: Results from the phase II NEWTON trial (ENGOT-ov49).

BACKGROUND

Retrospective analyses of niraparib trials showed that baseline platelets and weight were associated with occurrence of G ≥ 3 thrombocytopenia. A rational adjustment of dose to reduce adverse reactions (RADAR) strategy was never prospectively compared with standard dose.

METHODS

NEWTON aimed to evaluate the safety of niraparib RADAR dosing strategy in pts with platinum-sensitive, high-grade serous and endometroid ovarian, fallopian tube, or primary peritoneal cancer, as well as in pts with ovarian cancer and a germline or somatic BRCA mutation, irrespective of histologic subtype. Pts with weight≥ 58 and < 77 kg, or ≥ 77 kg with platelet count < 150,000/μL were randomized to receive niraparib 200 mg (RADAR) or 300 mg (standard). Pts < 58 kg were assigned to 200 mg (RADAR), and pts ≥ 77 kg with baseline platelet count ≥ 150,000/μL were assigned to 300 mg (RADAR). For pts assigned to 200 mg, in the absence of thrombocytopenia, severe neutropenia or anemia within cycle 3, dose escalation to 300 mg was considered at cycle 4. The primary endpoint was G ≥ 3 thrombocytopenia within cycle 3.

RESULTS

48 pts were randomized to RADAR or standard dose (300 mg/day) and 34 pts were assigned to RADAR without randomization. A total of 58 pts was included in the entire RADAR cohort. In the randomized part, a lower G≥ 3 thrombocytopenia incidence was observed in the RADAR compared to standard arm (4.2%, vs 41.7%, corresponding to a difference of -37.5%, 72%CI -49.2; -25.8, Z-test p= 0.0044). In the RADAR cohort, 6 pts out of 57 had G≥ 3 thrombocytopenia (10.5%, 70% CI: 5.2-18.6;). Median PFS was 10.3 and 11.7 months in the randomized RADAR and 300 mg arms. The median PFS in the entire RADAR cohort was 10.0 months.

CONCLUSIONS

Niraparib RADAR dosing is associated with a lower incidence of severe thrombocytopenia.

CLINICALTRIALS: gov number: NCT03891576.