Niraparib Showcases Improved Health-Related QOL, Reduced Pain Burden in mCRPC

Niraparib (Zejula) improved or maintained health-related quality of life (HRQOL), pain intensity, and pain interference in patients with advanced or metastatic castration-resistant prostate cancer (mCRPC), including those with BRCA gene alterations, according to the final analysis of the GALAHAD trial (NCT02854436) that was presented at the 47th Annual Oncology Nursing Society (ONS) Congress.

“In patients with advanced mCRPC and HRR gene alterations, niraparib improved or maintained overall HRQOL measures as assessed by the [Functional Assessment of Cancer Therapy-Prostate] total score, and pain intensity and pain interference as measured using the [Brief Pain Inventory-Short Form],” lead study author Minh Tran of Kaiser Permanente said in a virtual poster presentation during the meeting. “These data provide valuable information for clinicians and nurses to consider while caring for patients receiving niraparib for advanced prostate cancer.”

The open-label, international, phase 2 GALAHAD trial evaluated single-agent niraparib in patients with mCRPC and HRR gene alterations who progressed on prior taxane-based chemotherapy and androgen receptor inhibition. Niraparib was given orally at 300 mg daily and patients were stratified by the type of HRR gene alteration (BRCA cohort [BRCA1 or BRCA2]) or other HRR cohort (ATM, FANCA, PALB2, CHEK2, BRIP1, or HDAC2).

Previous data from GALAHAD, which were published in The Lancet, showcased meaningful clinical activity.2 At a median follow-up of 10.0 months (interquartile range, 6.6-13.3), evaluable patients with BRCA alterations and measurable disease (n = 76) achieved an objective response rate (ORR) of 34.2% (95% CI, 23.7%-46.0%) with the PARP inhibitor. In this cohort, 3% experienced a complete response (CR), and 32% had a partial response (PR).

Among evaluable patients with non–BRCA-altered measurable disease (n = 47), niraparib produced an ORR of 10.6% (95% CI, 3.5%-23.1%); here, no CRs were achieved, and 11% experienced PRs.

In the findings presented at the ONS Congress, investigators reported on the HRQOL outcomes, which was a prespecified exploratory end point in GALAHAD. Specifically, they evaluated the effect that niraparib had on overall HRQOL, pain intensity, and pain interference in patients with advanced mCRPC and HRR gene alterations.

Patient-reported outcomes (PROs) were assessed in all patients who had completed the baseline assessment and at least 1 postbaseline assessment. HRQOL was assessed on day 1 of cycles 3, 5, 7, and 10 with the following PROs:

1. Functional Assessment of Cancer Therapy-Prostate (FACT-P), which assessed patient’s self-reported functional status, well-being, and prostate cancer–related symptoms;
2. Brief Pain Inventory-Short Form (BPI-SF), which measured pain intensity and interference—which includes how much pain interferes with recent daily functions, such as general activity, walking, work, mood, enjoyment of life, relations with others, and sleep;
3. Baseline HRQOL changes were compared for BRCA vs other HRR patients through a mixed-effects model for repeated measures (MMRM).

PROs were categorized by improved (FACT-P, change from baseline [CFB] ≥10; BPI-SF, CFB ≤-0.5 standard deviation [SD]), stable (FACT-P, -10 < CFB <10; BPI-SF, -0.5 SD < CFB <0.5 SD), or worsened (FACT-P, CFB ≤-10; BPI-F, CFB ≥0.5 SD).

The median time to first deterioration in PROs was estimated by a Kaplan-Meier technique and was determined by meaningful change threshold values.

A total 221 patients were eligible for analysis, and most patients completed PRO assessments from baseline through cycle 10. Demographic and baseline characteristics were similar between the 2 cohorts in the intent-to-treat population.

In the BRCA cohort (n = 142), the median age was 67.0 years (range, 46-86) and patients had an ECOG performance status (PS) of 0 (33.8%), 1 (54.9%), or 2 (11.3%). A total 53.5% of patients had measurable disease status, a mean FACT-P total score of 21.5, a mean BPI-SF pain intensity score of 2.3, and a BPI-SF pain interference score of 2.7 at baseline.

In the other HRR cohort (n = 81), the median age was 70.0 years (range, 52-88) and the ECOG PS was 0 (22.2%), 1 (58.0%), or 2 (19.8%). Here, 58.0% of patients had measurable disease status and the mean FACT-P total score at baseline was 22.1, the BPI-SF pain intensity score was 2.3, and the BPI-SF pain interference score was 2.5.

Findings showed that patients generally demonstrated stable or improved overall HRQOL in FACT-P MMRM, and overall HRQOL was improved in the BRCA cohort following 3 cycles of niraparib (6.03). In the other HRR cohort, patients overall remained stable until cycle 10 (–5.10).

Additionally, patients in the BRCA cohort were more likely to experience clinically meaningful improvements in overall HRQOL vs those in the other HRR cohort. In distributions of FACT-P total change from baseline categories, this was seen in baseline to cycle 3 (OR, 2.40), baseline to cycle 5 (OR, 4.42), baseline to cycle 7 (OR, 2.01), and baseline to cycle 10 (OR, 1.69).

Furthermore, patients demonstrated stable or improved BPI-SF MMRM pain intensity scores, with rapid reduction reductions in scores seen in both cohorts. While those in the BRCA cohort experienced greater early pain relief (cycle 3, –1.06; cycle 5, ­–0.88), the mean pain intensity reductions were similar between cohorts by cycle 7 (BRCA, –0.61 vs other HRR, –0.53). Additionally, more patients in the BRCA cohort showed stable or improved pain intensity score compared with those in the other HRR cohort through to cycle 7.

Investigators also looked at BPI-SF MMRM pain interference scores. Both cohorts experienced rapid reductions in pain interference, but greater reductions in pain interference were seen in the BRCA cohort vs the other HRR cohort up to cycle 10. Regarding distribution of BPI-SF pain interference change from baseline categories by cohort, more patients in the BRCA cohort were stable or improved for most cycles vs the other HRR cohort.

Investigators also evaluated a Kaplan-Meier plot of time to deterioration in the FACT-P total score. The median time to deterioration in the FACT-P total score was longer in the BRCA cohort at 8.31 months vs 3.71 months in the other HRR cohort. With regard to the Kaplan-Meier plot of time to deterioration in pain interference subscale, most patients overall did not experience clinically meaningful worsening of pain intensity or pain interference.

References

1. Tran M, Olivier K, Liu Y, et al. Effects of niraparib on health-related quality of life in the final analysis of the GALAHAD study in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations. Presented at: 47th Annual Oncology Nursing Society Congress; April 27-May 1, 2022; Anaheim, CA. Abstract P392.
2. Smith MR, Scher HI, Sandhu S, et al. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial. Lancet. 2022;23(3):362-373. doi:10.1016/S1470-2045(21)00757-9