Top news of the week in oncology, and cancer drug development.
FDA Grants Rucaparib Priority Review in Ovarian Cancer
The FDA has granted a priority review to a new drug application for rucaparib as a treatment for patients with BRCA-positive advanced ovarian cancer who have received at least 2 prior lines of chemotherapy. The application is based on data from 106 patients across 2 trials, including the ARIEL2 study. In a pooled analysis of data from the studies, the objective response rate was 54% (95% CI, 44-64) with rucaparib.
The complete response rate was 9% and the partial response rate was 45%. The median duration of response was 9.2 months (95% CI, 6.6-11.6). ORR rates were similar, regardless of whether patients had germline or somatic BRCA mutations, or mutations of the BRCA1 gene versus the BRCA2 gene.
Progressive disease occurred in 9 of the 106 patients. Rucaparib previously received a breakthrough therapy designation from the FDA in this setting in April 2015. The FDA is scheduled to make a final decision on the application for the PARP inhibitor by February 23, 2017, as part of the Prescription Drug User Fee Act.
Pacritinib Shows Mixed Results for Advanced Myelofibrosis
Treatment with pacritinib significantly reduced spleen volume but failed to improve total symptom score compared with best available therapy for thrombocytopenic patients with high-risk myelofibrosis, according to topline findings for the coprimary endpoints of the phase III PERSIST-2 trial. In the randomized trial, 311 patients with platelet counts of ≤100,000/μL were treated with pacritinib or best available therapy, which may have included ruxolitinib.
Efficacy was assessable for 221 patients with at least 24 weeks of follow-up, in which pacritinib showed a statistically significant ≥35% reduction in spleen volume versus best available therapy (P <.01); however, a 50% reduction in symptoms was not seen with pacritinib (P = .0791). Despite missing the coprimary endpoint of symptom control, principal investigator Srdan Verstovsek, MD, PhD, labeled the results encouraging, due to the high unmet need for this population of patients.
The negative findings followed a clinical hold placed on the trial in February 2016, following reports of deaths related to intracranial hemorrhage, cardiac failure, and cardiac arrest. The most common adverse events reported in the PERSIST-2 trial were diarrhea, nausea, and vomiting. Additionally, the company noted that cardiac and bleeding AEs were similar between the pacritinib and best available therapy arms.
MammaPrint Utility Displayed in Phase III MINDACT Study
Approximately 46% of patients with breast cancer at high risk for recurrence but low genomic risk with the 70-gene breast cancer recurrence assay (MammaPrint) might not require adjuvant chemotherapy, according to prospective 5-year results of the MINDACT trial published in The New England Journal of Medicine.
The patients classified as low risk were shown to have prolonged survival regardless of receiving adjuvant chemotherapy, giving MammaPrint level 1A clinical evidence and confirming its clinical utility. Initial results of the MINDACT trial were presented at the 2016 AACR Annual Meeting, which showed that MammaPrint demonstrated a high level of accuracy at identifying a large subset of women with clinically high-risk early stage breast cancer for whom adjuvant chemotherapy was unlikely to produce benefit.
In the 1550 patients with high clinical risk and low genomic risk, the 5-year survival rate without distance metastasis was 94.7% for those who did not receive chemotherapy (95% CI, 92.5-96.2). In those who did receive chemotherapy, the survival difference was 1.5 percentage points, with the rate being lower without chemotherapy.
CASTOR Results Published in NEJM
Phase III findings from the CASTOR study were published in The New England Journal of Medicine showing that daratumumab significantly improved progression-free survival when added to bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. In the study, which included 498 patients who had relapsed or refractory multiple myeloma, the 12-month PFS rate was 60.7% for patients who received the combination of daratumumab, bortezomib, and dexamethasone versus 26.9% in those who received bortezomib and dexamethasone alone.
After a median follow-up period of 7.4 months, the median PFS was not reached in the daratumumab group and was 7.2 months in the control group (HR, 0.39; 95% CI, 0.28-0.53; P <.0001). More patients had partial responses (59.2% vs 29.1%, P <.001) or complete responses (19.2% vs 9.0%, P = .001) with the addition of daratumumab. The overall response rate was also higher with the addition of daratumumab, with an 82.9% ORR in the daratumumab group compared with 63.2% in the control group (P <.001).