Men with castration-resistant prostate cancer (CRPC) and bone metastases (BM) will often have debilitating pain that impacts every aspect of their daily functioning thus significantly diminishing their quality of life (QoL). Finding the best drug or treatment to control the pain will allow men to have a more complete and fulfilling life as well as increase their QoL.
Phase III clinical trials have demonstrated the superiority of the drug Denosumab over Zoledronic acid (Za) in delaying or preventing the development of skeletal-related events which is defined as pathological fractures, having radiation or surgery to the bone and spinal cord compression in men with CRPC and who have BM. An ad-hoc analysis of this trial showed that Denosumab is superior to ZA for pain interference (PI) and cancer specific quality of life (QoL), focusing on the subgroup of men with no or mild pain at baseline.
The subjects were men with CRPC and BM who had no prior IV bisphosphonate treatment. They were randomized to receive either Denosumab (120 mg+IV placebo) or placebo+IV Zoledronic Acid 4mg (adjusted for creatinine clearance) every four weeks. All the men were instructed to take calcium and vitamin D supplements.
The Brief Pain Inventory–Short Form (BPI-SF) was used to assess their pain perception. The pre-specified clinically meaningful time of a greater than or equal to two point increase from baseline in PI score (overall, physical, and emotional subdomains) was determined for the men receiving Denosumab or ZA treatment. The men also completed the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire at baseline and at each monthly visit to determine their QoL scores.
Of the 1,901 men enrolled (n=950, Denosumab; n=951, ZA), 1,045 (55%) had no/mild pain at baseline. Compared with ZA, Denosumab therapy delayed the time to a greater than or equal to two point increase from baseline in pain inventory for the overall score (HR=0.83 [0.71, 0.98]; P=0.023), physical (HR=0.87 [0.75, 1.02]; P=0.077) and emotional (HR=0.83 [0.71, 0.97]; P=0.020) subdomains.
Over a period of 18 months, more ZA-treated men than Denosumab-treated men experienced a greater than or equal to five point decrease in FACT-G total scores (average relative difference=6.8%, range -9.4 to 14.6%) or had a significantly worsening of QoL.
Denosumab, which has already shown its ability to delay the initial onset of skeletal related events, also significantly delayed the time to worsening of pain interference and maintained a higher overall QoL (FACT-G) compared to ZA in CRPC patients with BM.
Should you be having Denosumab instead of Zoledronic acid? Speak with your doctor about this question.
Clinical trial information: NCT00321620.
J Clin Oncol 32, 2014 (suppl 4; abstr 12); Donald Patrick, Charles S. Cleeland, Lesley Fallowfield, Matthew Raymond Smith, Laurence Klotz, Stephane Oudard, Gavin M. Marx, Rachel Wei, Katarina Ohrling, Yi Qian
Joel T. Nowak, M.A., M.S.W.