October 22, 2023
Final MAGNITUDE Analysis Supports New Standard of Care for BRCA+ mCRPC
By Catlin Nalley
The 3-year update and final analysis of the Phase III MAGNITUDE study (NCT03748641) confirms that niraparib with abiraterone acetate plus prednisone (AAP) should be considered a new standard of care for the first-line treatment of patients with BRCA+ metastatic castration-resistant prostate cancer (mCRPC).
These findings, which were presented during the European Society for Medical Oncology (ESMO) Congress 2023, held October 20-24 in Madrid, Spain, showed that not only did overall survival favor this combination, but niraparib with AAP also led to improvements in time to symptomatic progression, time to cytotoxic chemotherapy, and patient-reported outcomes (Abstract LBA85).
Previously reported results of the MAGNITUDE study demonstrated a significantly improved radiographic progression-free survival among patients who received niraparib with abiraterone acetate plus prednisone.
“The study presented at ESMO is the final event-driven analysis of the Phase III MAGNITUDE study after 3 years of follow-up, evaluating niraparib with abiraterone acetate plus prednisone in patients with metastatic castration-resistant prostate cancer with BRCA alterations,” noted study author Kim N. Chi, MD, FRCPC, Medical Oncologist at the Vancouver Cancer Centre and Vancouver Prostate Centre at the BC Cancer Agency-Vancouver in Canada. Data shared at ESMO include mature overall survival data and prespecified multivariate analysis for overall survival, addressing baseline imbalances.
Study Methodology
MAGNITUDE was designed to define the patient population most likely to benefit from the combination of niraparib with AAP through prospective determination of patients' biomarker status, according to Chi.
“Patients with metastatic castration-resistant prostate cancer in the study were tested via either tissue or plasma assay for homologous recombination repair (HRR+) genetic mutations based on a nine-gene panel to determine biomarker status prior to randomization,” he explained.
Eligible patients with HRR+ metastatic castration-resistant prostate cancer (n=423) were randomized 1:1 to niraparib with AAP (n=212) or placebo with APP (n=211) as a first-line therapy. Among these patients, 225 were BRCA+, the largest BRCA+ population studied to date in a Phase III mCRPC study, Chi noted.
“At this final analysis, secondary endpoints of overall survival and time to cytotoxic chemotherapy were formally assessed,” the study authors stated. “Updates to time to symptomatic progression and patient-reported outcomes in BRCA+ patients and to safety for all HRR+ patients are also reported.”
Key Findings
Of the 225 BRCA+ patients evaluated in this final analysis, 113 received niraparib with abiraterone acetate plus prednisone. The median follow-up was 35.9 months.
“Key results showed an overall survival benefit favoring patients who received niraparib plus AAP compared to the placebo plus AAP arm,” reported Chi. “The overall survival benefit was more pronounced on a preplanned multivariable analysis controlling for imbalances in prognostic factors which favored the control arm.
“Continued improvement in time to symptomatic progression and time to cytotoxic chemotherapy was also observed in patients who received niraparib and abiraterone acetate plus prednisone compared to patients randomized to placebo plus abiraterone acetate plus prednisone,” he added, while also noting that in this final analysis no new safety signals and no cases of myelodysplastic syndrome or acute myeloid leukemia were observed among patients in the niraparib and AAP arm.
“These final results underscore the significance of this new treatment option for patients with newly diagnosed mCRPC with BRCA+ mutations,” Chi told Oncology Times. “There will be further analyses presented at upcoming medical conferences on quality of life and other aspects of the MAGNITUDE study.”
Additional Research
During ESMO, other data related to the MAGNITUDE study were also shared during a poster presentation (Abstract 1806P).
“The efficacy by assay study intended to confirm any difference in identifying HRR+/BRCA+ patients by either tissue or plasma ctDNA assays,” Chi explained. “Plasma ctDNA assays are a minimally invasive and convenient new liquid biopsy method to test for HRR gene mutations in patients with mCRPC.”
Chi reported that 159 patients were HRR+ with both assays (96 were BRCA+). Additionally, he noted that 124 HRR+ patients (62 BRCA+) were tissue-positive but plasma-negative, and 38 HRR+ patients (17 BRCA+) were positive with plasma, but tissue-negative. “Hazard ratios for endpoints, except overall survival, had p<0.05 for patients BRCA+ by either assay, with similar results for HRR+ patients.
“Clinically meaningful benefit from niraparib with abiraterone acetate plus prednisone are similar for BRCA+ patients detected by either tissue or plasma-based assays,” he reported. “Positivity by either test is sufficient to guide treatment decisions.”
Catlin Nalley is a contributing writer.