Ovarian cancer: AR1ZE and CHAR1ZMA

Professor Toon Van Gorp, an oncological gynaecologist from the University of Leuven, Belgium, discusses two studies presented at SGO 2024 in San Diego. The AR1ZE and CHAR1ZMA studies examined the utilization of niraparib as a first-line maintenance treatment in ovarian cancer, featuring real-world data from the Flatiron Health electronic health record database.

The AR1ZE study focused on patients receiving niraparib, following the inclusion/exclusion criteria of the PRIMA study, with the additional inclusion of a small cohort of stage 3 ovarian cancer patients without residual disease who were not part of the PRIMA study. In the U.S., these patients can receive niraparib off-label. Among 453 patients receiving niraparib, 63 received it off-label. The study aimed to investigate potential differences in characteristics and survival outcomes between these patients and those treated according to PRIMA criteria.

Off-label patients were exclusively stage 3, in contrast to those included based on PRIMA criteria, who comprised both stage 3 and stage 4 patients. Off-label patients tended to be younger and had higher rates of HRD positivity and BRCA mutations. They exhibited nearly double the time to the next treatment (25 vs. 12 months) and PFS compared to those treated according to PRIMA criteria. This suggests a more favourable prognosis for off-label patients, raising the question of whether niraparib should be considered for patients who were excluded from the PRIMA study.

In a similar population, the CHAR1ZMA study analysed 236 patients with known HRD status receiving niraparib, comparing HRD-positive BRCA wild-type and HRD-positive BRCA mutated patients. Notably, 61% of patients were HRD-positive, surpassing the 50% rate observed in other studies. As expected, approximately half of the HRD-positive patients had a BRCA mutation.

Niraparib administration can be initiated at different dose levels, ranging from 100-200-300 mg. Interestingly, in one out of four patients, the highest dose was used while half of them started at the dose level of 200 mg. This is a clear indication that physicians are already using the individualized starting dose, taking baseline weight and baseline platelet count into account, consistent with Belgian practice. 

Both HRD-positive populations, with or without BRCA mutations, exhibited similar baseline characteristics. However, BRCA mutated patients demonstrated double the time to the next treatment and PFS compared to wild-type patients (25 vs. 14 months). In conclusion, all HRD-positive patients benefit from niraparib treatment but the biggest benefit is achieved in BRCA mutated patients. Additionally, treatment decisions are increasingly tailored to individual patients, considering factors beyond weight and platelet count, such as overall health status.