Photo courtesy of Janssen
Results of the phase 3 CASTOR trial suggest that adding daratumumab to treatment with bortezomib and dexamethasone can improve progression-free survival (PFS) in patients with previously treated multiple myeloma (MM).
Compared to patients who received only bortezomib and dexamethasone, those who received daratumumab as well had a higher response rate and longer PFS, but they also had a higher incidence of grade 3/4 adverse events (AEs).
These results were recently published in NEJM. They were previously presented at the 2016 ASCO Annual Meeting. The CASTOR trial was funded by Janssen Research & Development.
The trial enrolled 498 patients with relapsed or relapsed and refractory MM. Patients were randomized to receive bortezomib (1.3 mg/m2) and dexamethasone (20 mg) alone (control arm) or in combination with daratumumab (16 mg/kg).
Baseline characteristics were well balanced between the treatment arms. Across both groups, the median patient age was 64 (range, 30 to 88), the median time since MM diagnosis was 3.8 years, and the patients had received a median of 2 (range, 1 to 10) previous lines of therapy.
Efficacy
The overall response rate was significantly higher in the daratumumab arm than the control arm—82.9% and 63.2%, respectively (P<0.001). The rate of complete response or better was higher in the daratumumab arm as well—19.2% and 9.0%, respectively (P=0.001).
After a median follow-up of 7.4 months, the median PFS was not reached in the daratumumab arm and was 7.2 months in the control arm (hazard ratio=0.39, P<0.001). The estimated 12-month PFS was 60.7% and 26.9%, respectively.
Overall survival was not reached in either treatment arm.
This trial was unblinded after meeting its primary endpoint of improved PFS in this interim analysis. Based on the recommendation of an independent data monitoring committee, patients in the control arm were offered the option to receive daratumumab following confirmed disease progression.
Safety
AEs occurred in 98.8% of patients in the daratumumab arm and 95.4% of patients in the control arm. Grade 3/4 AEs occurred in 76.1% and 62.4%, respectively.
There was a higher incidence of the following AEs in the daratumumab arm than the control arm—thrombocytopenia (58.8% vs 43.9%), neutropenia (17.7% vs 9.3%), lymphopenia (13.2% vs 3.8%), peripheral sensory neuropathy (47.3% vs 37.6%), bleeding events (7.0% vs 3.8%), and secondary primary cancers (2.5% vs 0.4%).
Infusion-related reactions associated with daratumumab were reported in 45.3% of patients. These reactions were mostly grade 1 or 2.
The percentage of patients who discontinued treatment because of at least 1 AE was similar between the daratumumab and control arms (7.4% and 9.3%, respectively).
