Maintenance niraparib fails to improve PFS in advanced urothelial cancer

The Meet-URO12 trial of maintenance niraparib in advanced urothelial cancer patients without progression after first-line chemotherapy failed to meet its primary endpoint of improvement in progression-free survival (PFS).

Homologous recombination deficiency (HRD) is present in 10–25% of advanced urothelial carcinomas and sensitises cancer cells to both platinum-based chemotherapy and PARP inhibitors [1,2]. This offers a rationale for maintenance therapy with a PARP inhibitor in patients with advanced urothelial carcinoma who obtained an objective response or stable disease with first-line platinum-based chemotherapy.

Meet-URO12 (NCT03945084) is a phase 2, prospective, randomised, open-label, multicentre study conducted in patients with locally advanced or metastatic urothelial carcinoma who show no evidence of progression after 4–6 cycles of first-line platinum-based chemotherapy (cisplatin or carboplatin). Participants (n=58) were 2:1 randomised to receive niraparib plus best supportive care (BSC) versus BSC alone as maintenance therapy. The primary endpoint was PFS. Dr Francesca Vignani (Ordine Mauriziano Hospital, Italy) reported the results [3].

The trial accrual was stopped prematurely due to the availability of avelumab in the same setting. Most patients had a partial response (50%) or stable disease (45%) after platinum-based chemotherapy. Median PFS was 2.1 months in the niraparib plus BSC arm and 2.4 months in the BSC arm (HR 0.92; P=0.81). The 6-month PFS rate was 28.2% in the niraparib plus BSC arm and 26.3% in the BSC-alone arm. The median duration of response was 2.0 months in both arms.

The safety profile of niraparib was consistent with that observed in other solid tumours. Treatment-emergent adverse events of grade 3 or 4 were observed in 65.8% of patients treated with niraparib plus BSC and 15.8% of patients receiving BSC alone. The most common events of this severity in the niraparib arm were fatigue (15.8%), anaemia, and thrombocytopenia (both 10.5%).

Dr Vignani concluded that Meet-URO12 did not meet its primary endpoint. “Maintenance niraparib plus BSC did not prolong PFS, as compared with BSC alone, in patients with urothelial cancer without progression after first-line platinum-based chemotherapy. Future studies could evaluate potential synergy of PARP inhibitors in combination with other therapies, such as immune checkpoint inhibitors,” said Dr Vignani.

1. Heeke AL, et al. JCO Precis Oncol. 2018;2018:PO.17.00286.
2. Taber A, et al. Nat Commun 2020;11:48–58.
3. Vignani F, et al. Randomized phase II study of niraparib plus best supportive care (BSC) versus BSC alone as maintenance treatment in patients with advanced urothelial carcinoma (UC) whose disease did not progress after first-line platinum-based chemotherapy (PBCT): The Meet-URO12 trial. Abstract 442, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April, 202225 March, 2024