First-line rucaparib boosts PFS in ovarian cancer regardless of HRD status

First-line rucaparib maintenance therapy extends progression-free survival (PFS) in patients with ovarian, fallopian tube, or primary peritoneal cancer, according to results of the phase III ATHENA-MONO trial presented at the ESMO Gynaecological Cancers Conference 2022.

Participants in the international, double-blind ATHENA trial were patients with newly diagnosed, stage III–IV, high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer and ECOG performance status 0–1 who had complete or partial response to frontline platinum doublet chemotherapy and cytoreductive surgery. They were randomized to receive rucaparib (600 mg BID) + nivolumab (480 mg; arm A), rucaparib (600 mg BID) + placebo (arm B), nivolumab (480 mg) + placebo (arm C), or placebo (arm D) for ≤24 months.

The present ATHENA-MONO analysis compared arms B and D (427 and 111 patients, respectively; median age 61 years, 77–78 percent White). Seventy-six and 70 percent of patients, respectively, were of FIGO* stage III. The most common cancer was epithelial ovarian (79 and 77 percent, respectively), followed by fallopian tube cancer (12 and 16 percent, respectively). A total of 185 and 49 patients, respectively, were homologous recombination deficiency (HRD) positive. The patients were followed up for a median 26 months, with patients in the rucaparib and placebo arms receiving treatment for a median 14.7 and 9.9 months, respectively.

There was a significant improvement in investigator-assessed PFS with rucaparib vs placebo, both in the intent-to-treat (ITT) population (median 20.2 vs 9.2 months; hazard ratio [HR], 0.52, 95 percent confidence interval [CI], 0.40–0.68; p<0.0001) and HRD population (median 28.7 vs 11.3 months; HR, 0.47, 95 percent CI, 0.31–0.72; p=0.0004). [ESMO Gynaecological Cancers Conference 2022, session: Clinical Trial Highlights]

The PFS benefits with rucaparib vs placebo appeared consistent regardless of BRCA mutation and HRD status, remarked study author Dr Rebecca Kristeleit from the Guy’s and St Thomas’ NHS Foundation Trust, London, UK.

In the ITT population, one patient in the rucaparib group had a complete response, and 19 and one in the rucaparib and placebo groups, respectively, had partial response. Duration of response was greater with rucaparib vs placebo (median 22.1 vs 5.5 months [ITT]; median 16.7 vs 5.5 months [HRD]).

Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 60.5 and 22.7 percent of rucaparib and placebo recipients, respectively. TEAEs led to treatment interruption in 60.7 and 20.0 percent, respectively, dose reductions in 49.4 and 8.2 percent, respectively, and discontinuations in 11.8 and 5.5 percent, respectively. There were two deaths due to TEAEs in the rucaparib group, though neither were considered related to treatment. Two patients in the rucaparib group experienced myelodysplastic syndrome/acute myeloid leukaemia.

The most common grade ≥3 TEAEs in the rucaparib group were anaemia or decreased haemoglobin levels (28.7 percent), neutropenia or decreased neutrophil count (14.6 percent), and increased alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels (10.6 percent).

“AST/ALT elevations were not accompanied by significant changes in bilirubin and there were no reports of drug-induced liver toxicity as defined by Hy’s Law,” said Kristeleit. “[In addition,] >70 percent of patients continued to receive ≥500 mg BID rucaparib through month 12.”

“Patients with measurable disease at baseline have further tumour reduction with rucaparib,” Kristeleit added, noting that overall survival results are currently immature.

“[In conclusion,] rucaparib first-line maintenance treatment significantly improves PFS irrespective of HRD status,” she said.