Treatment of recurrent ovarian cancer

Individual dosing of PARP inhibitor niraparib is associated with less adverse events, results from the NORA study showed. NINJA and INOVATYON demonstrated that neither nivolumab monotherapy nor trabectedin improve survival in patients with recurrent ovarian cancer.

In patients with platinum-sensitive recurrent ovarian cancer, the PARP inhibitor niraparib demonstrated a significant benefit in progression-free survival (PFS) compared with placebo, regardless of the presence or absence of BRCA mutations or HRD status [1]. The starting dose in this trial was 300 mg daily. However, a retrospective analysis indicated that an individualised starting dose based on baseline body weight and platelet count may improve the safety profile without compromising efficacy [2]. Therefore, in the phase 3 NORA trial, patients in the niraparib arm received an individualised starting dose of niraparib [3].

The study enrolled 265 patients; 88 were allocated to receive placebo, 177 to receive niraparib. The starting dose was 200 mg for patients with baseline body weight <77 kg or platelet count <150,000/μL; otherwise, 300 mg. Like in the NOVA registration trial, niraparib significantly improved median PFS compared with placebo in NORA (18.3 vs 5.4 months; HR 0.32; 95% CI, 0.23-0.45; P<0.0001). However, individualised dosing was associated with a decrease in haematologic grade 3/4 adverse events.

Two studies evaluating new second-line treatment options for patients with recurrent ovarian cancer, did not meet their primary endpoint. In INOVATYON, 617 patients with ovarian cancer who relapsed on prior platinum therapy and had a platinum-free interval between 6-12 months were randomised 1:1 to receive pegylated liposomal doxorubicin (PLD) plus carboplatin or PLD plus trabectedin (1.1 mg/m² every 3 weeks). At a median follow-up of 44 months, 466 deaths were observed [4]. The median PFS was 9.0 and 7.5 months in the carboplatin and trabectedin arm, respectively (HR 1.26; P=0.005), However, the median overall survival (OS; primary endpoint) was not different between the 2 arms (21.3 vs 21.5 months; HR 1.10; P=0.284).

A phase 2 trial has supported the efficacy and safety of nivolumab in platinum-resistant ovarian cancer [5]. In the phase 3 NINJA trial, 316 patients with platinum-resistant ovarian cancer were randomised 1:1 to receive nivolumab (240 mg every 2 weeks) or chemotherapy (gemcitabine or PLD) until disease progression or unacceptable toxicity [6]. Median OS was 10.1 months with nivolumab versus 12.1 months with chemotherapy (HR 1.0; 95% CI 0.8-1.3; P=0.808). Median PFS was 2.0 versus 3.8 months, respectively (HR 1.5; 95% CI 1.2-1.9; P=0.002). The rate of treatment-related grade 3/4 adverse events was 22.4% with nivolumab and 68.4% with chemotherapy.

1. Mirza MR, et al. N Engl J Med 2016;375:2154-2164.
2. Berek JS, et al. Ann Oncol 2018;29:1784-1792.
3. Wu X, et al. Individualized starting dose of niraparib in Chinese patients with platinum-sensitive recurrent ovarian cancer (PSROC): A randomized, double-blind, placebo-controlled, phase III trial (NORA). ESMO 2020 Virtual Meeting, abstract LBA29.
4. Colombo N, et al. INOVATYON study: Randomized phase III international study comparing trabectedin/PLD followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line. ESMO 2020 Virtual Meeting, abstract LBA30.
5. Hamanishi J, et al. J Clin Oncol 2015;33:4015-4022.
6. Omatsu K, et al. Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant (advanced or recurrent) ovarian cancer: Open-label, randomized trial in Japan (NINJA trial). ESMO 2020 Virtual Meeting, abstract 807O.

Posted on 25 November, 202027 March, 2024