Doublet maintenance therapy does not outperform monotherapy in ovarian cancer

Adding nivolumab to rucaparib maintenance therapy did not improve progression-free survival (PFS) in patients with ovarian cancer, outcomes of the phase 3 ATHENA-COMBO trial demonstrated.

Previously, the ATHENA-MONO substudy (NCT03522246) previously showed that maintenance therapy with rucaparib monotherapy significantly improved survival in patients with stage III–IV, high-grade ovarian cancer, compared with placebo [1]. Concurrently, ATHENA-COMBO evaluated the safety and efficacy of maintenance therapy with rucaparib plus nivolumab in this population. Prof. Bradley Monk (University of Arizona, AZ, USA) presented the results [2].

In ATHENA-COMBO, the rucaparib arm of ATHENA-MONO (n=427) was used as a control arm. In the rucaparib plus nivolumab arm, 436 participants were treated for up to 24 months.

Adding nivolumab to maintenance rucaparib did not improve outcomes. The median PFS was 15.0 months on doublet therapy versus 20.2 months in the rucaparib alone arm (HR 1.29; 95% CI 1.08–1.53). The 4-year PFS rate was 33% versus 26%. Monotherapy favoured PFS in all prespecified subgroups, e.g. stratified by BRCA or PD-L1 status. In addition, no benefit of doublet maintenance therapy was seen in overall survival (OS). Median OS was 49.4 and 58.0 months in the doublet and monotherapy arms, respectively.

Moreover, doublet maintenance therapy came with more adverse events, more dose interruptions, and more discontinuations and deaths due to adverse events.

To explain the inferiority of the doublet maintenance therapy, Prof. Monk pointed out that the median exposure to rucaparib was 8.4 months in the doublet arm, while this was 14.7 months in the monotherapy arm. “So, the monotherapy group got more rucaparib.”

“Nivolumab in combination with rucaparib was associated with increased toxicity and did not extend the PFS benefit of rucaparib monotherapy as first-line maintenance treatment in patients with ovarian cancer,” concluded Prof. Monk.

1. Monk BJ, et al. J Clin Oncol. 2022;40:3952-3964.
2. Monk BJ, et al. ATHENA-COMBO, a phase III, randomized trial comparing rucaparib (RUCA) + nivolumab (NIVO) combination therapy vs RUCA monotherapy as maintenance treatment in patients (pts) with newly diagnosed ovarian cancer (OC). Abstract LBA30, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024