Drug Toxicity May Drive Early Niraparib Discontinuation in Ovarian Cancer

The most frequent cause of early discontinuation of niraparib for epithelial ovarian cancer was drug toxicity.

Drug toxicity was the most common reason for early discontinuation of first-line maintenance monotherapy with niraparib (Zejula) among patients with epithelial ovarian cancer, according to data from the real-world CHAR1ZMA study. ¹

Other causes for early discontinuation of niraparib included starting on a dose higher than an individualized starting dose and having less frequent dose modifications.

“Education for providers is needed on the importance of drug toxicity management, particularly during the first 90 days of treatment, and on the individualized starting dose,” said investigators in the study’s report in the International Journal of Gynecological Cancer.

The PARP inhibitor niraparib was first approved by the FDA as a maintenance treatment for epithelial ovarian cancer in April 2020.

Researchers conducting the CHAR1ZMA study analyzed data from electronic health records of 560 adult patients with epithelial ovarian cancer who received niraparib as a first-line monotherapy who had received no prior or second-line treatment, including other PARP inhibitors. Of the 560 patients in the study, 161 discontinued treatment early and 399 did not.

Patients included in this study started treatment between January 2017 and December 2022. Patients were diagnosed with ovarian cancer no earlier than January 2015.

The most common cause for discontinuation of niraparib was toxicity in 67.7% of patients who discontinued early compared with 18.1% in those who did not discontinue treatment early. Patients who discontinued treatment early were less likely to undergo dose modifications compared with non-early discontinuers (29.8% vs. 53.6%).

In contrast, the most common reason for discontinuing niraparib in non-early discontinuers was disease progression, which occurred less frequently in patients who discontinued treatment early (74.8% vs. 30.4%).

Homologous recombination deficient (HRd) tumors were present in 144 (25.7%) patients, and homologous recombination proficient (HRp) tumors or BRCA wild-type disease with unknown homologous recombination deficiency status were present in 389 (69.5%) of patients.

The median treatment duration overall was 7.2 months (95% CI, 6.0-8.1) in the overall patient population. The median treatment duration was 4.5 months longer in patients who did not discontinue early (11.7 months; 95% CI; 9.8-14.7).

In addition, the median treatment duration for patients in the HRd group was 11.6 months (95% CI, 7.8-16.1), and was 5.1 months longer in those who did not discontinue maintenance treatment early (16.7 months; 95% CI, 12.0-22.8).

Researchers also found that 46.8% (n = 262) of all patients in the study had a dose modification at some point in the duration of treatment. Dose modifications occurred less frequently in early discontinuers compared with those who did not discontinue early (29.8% vs. 53.6%).

A total of 87.5% and 12.5% of early discontinuers had 1 and 2 dose changes, respectively. Likewise, 68.7%, 23.3%, and 8.0% of other patients in the study who did not discontinue treatment early had 1, 2, and 3 or more dose modifications.

In all patients in the study, 329 (58.8%) were given niraparib at individualized starting doses (ISDs) based on body weight and platelet count, 103 (18.4%) patients received dosages lower than their ISDs, and 80 (14.3%) patients received doses higher than their ISDs. Of early discontinuers, 54.0% received ISDs, 17.4% received doses lower than their ISDs, and 17.4% received doses higher than their ISDs. In patients who did not discontinue treatment early, 60.7% were given niraparib at their ISD, 18.8% received a dose lower than their ISD, and 13.0% received a dose higher than their ISD.

“This suggests that early discontinuers may have missed opportunities to receive appropriate dose modifications,” observed researchers. “Taken together, these findings indicate that providers may benefit from education on effective and early clinical management of toxicity, such as using an individualized starting dose and dose modifications, allowing a patient to remain on first-line maintenance niraparib treatment longer and experience the full treatment benefit.”

Reference

Backes FJ, Boyle TAC, Lim J, et al. Real-world duration of first-line maintenance niraparib monotherapy in patients with epithelial ovarian cancer in the United States: the CHAR1ZMA study. Int J Gynecol Cancer. 2024;0(0):1-9. doi: doi.org/10.1016/j.ijgc.2024.100044