At this time, each of the agents is given in isolation, and when patients fail (and they always do), then we move on to the next agent. Yet, combination treatments are gaining prominence. Trying to leverage different mechanisms of action, combining agents may yield better outcomes than any individual treatment.
The multidisciplinary group from Ireland present their phase II safety and tolerability study of Radium-223 (R223) and enzalutamide (Enza) in 45 patients with mCRPC. They enrolled men with mCRPC, with metastases to bone with or without visceral/lymph node involvement who had progressed on androgen deprivation therapy (ADT). They did allow patients to have received prior docetaxel chemotherapy for hormone sensitive prostate cancer was allowed (per CHAARTED trial recommendations). All patients received 6 cycles of R223 (55 kBq/kg IV every 4 weeks) in combination with ENZA (160 mg oral daily), followed by ENZA alone until disease progression (PD), unacceptable toxicity or consent withdrawal. Their primary endpoint was safety for the 6 months of combination therapy – not oncologic outcomes.
Study schema is below:
Of the 45 patients enrolled, 42 pts (93.3%) received all 6 cycles of combination therapy.
Baseline characteristics: Median age 68, median PSA 73.2, Median Alk Phos 158.2, 98% had ECOG 0-1.
In terms of safety, only 13 pts (28.9 %) had grade (gr) 3/4 adverse events (AEs). The most frequent gr 3/4 AEs (Table) were neutropenia (n = 3, 6.6%) and fatigue (n = 3, 6.6%) followed by nausea, lower respiratory tract infection (LRTI), lymphocytopaenia, leukopaenia, hyperkalaemia, hypokalaemia, back pain, headache, urticaria, syncope and hypertension (all n = 1, 2.2%). Only 2 pts (4.4%) discontinued treatment due to AE – 1 patient with grade 3 LRTI and 1 patient with grade 2 nausea and pain. There were no therapy-related deaths.
In terms of outcome, only 1 patient discontinued due to symptomatic PD. However, they did not comment on oncologic responses at this time.
Based on these results, R223 in combination with ENZA appears to be well tolerated with acceptable early safety and toxicity profiles consistent with those seen when they are used as single agents and allowing for concomitant administration. Longer term follow-up with a focus on oncologic outcomes.
Presented by: Raymond S. McDermott, MD
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA