ORZORA: Maintenance olaparib shows benefit in BRCA-mutated ovarian cancer

Maintenance treatment with olaparib showed progression-free survival (PFS) benefit in patients with platinum-sensitive relapsed ovarian cancer (PSR OC), particularly those with somatic BRCA mutation (BRCAm), according to results of the ORZORA* trial presented at SGO 2021.

This open-label, single-arm, multicentre trial evaluated 181 patients with PSR OC who were screened for BRCA mutation (overall BRCAm cohort; n=145, median age 61.5 years), of whom 55 and 87 had confirmed somatic (sBRCAm cohort; median age 67 years) and germline mutations (gBRCAm cohort; median age 56 years), respectively. An exploratory analysis was performed which identified 33 patients with non-BRCA HRRm** (non-BRCA HRRm cohort; median age 64.0 years). Participants were given maintenance olaparib 400 mg twice daily until disease progression or treatment discontinuation. [SGO 2021, abstract 10503]

At a median follow-up of 22.3 months, the median PFS was comparable in the overall BRCAm, sBRCAm, and non-BRCA HRRm cohorts (18.0, 16.6, and 16.4 months, respectively). These findings were very similar to the previous results of Study 19*** and SOLO2⁺ trials, said lead author Dr Sandro Pignata from Istituto Nazionale Tumori in Napoli, Italy.

At 2 years, the proportion of patients who were free from disease progression was 39 percent in the overall BRCAm cohort, 33 percent in the sBRCAm cohort, and 26 percent in the non-BRCA HRRm cohort.

There was no difference in change in quality of life between the overall BRCAm and the sBRCAm cohorts (68.7 percent and 68.0 percent, respectively), with 21.8 percent and 21.3 percent improvements, respectively, from baseline.

Both the overall BRCAm and sBRCAm cohorts also showed comparable rates of treatment-emergent adverse events (TEAEs) of any grade (94.4 percent and 94.5 percent, respectively). “There were no surprising results and the data was very similar with what was already known from previous studies,” said Pignata.

The most frequent TEAEs reported were nausea (53.7 percent), fatigue (53.7 percent), and anaemia (42.4 percent), which were all as expected, Pignata noted.

“In conclusion, ORZORA showed, again, that olaparib had clinical activity, [in terms of PFS,] in patients with PSR OC and, in particular, that the activity in somatic BRCA-mutated patients was very similar to those that carry a germline mutation,” Pignata concluded.

“This is the largest sBRCAm cohort that have been investigated up to [date and showed] … a benefit for maintenance olaparib,” he noted.

“[Moreover,] the results in the additional exploratory cohort suggest that the selected population with [non-BRCA] HRRm [achieved a] clinical benefit that was very similar to those obtained in the [overall] BRCAm patients,” said Pignata.

*ORZORA: To assess the efficacy and safety of olaparib maintenance monotherapy in the treatment of ovarian cancer

**HRRm: Homologous recombination repair mutation

***Study 19: Assessment of efficacy of AZD2281 in platinum-sensitive relapsed serous ovarian cancer

⁺SOLO2: Olaparib treatment in BRCA mutated ovarian cancer patients after complete or partial response to platinum chemotherapy