Lack of correlation between the dose of fentanyl sublingual spray for breakthrough cancer pain and the dose of around-the-clock opioid for persistent pain

Abstract

Fentanyl sublingual spray is indicated for the treatment of breakthrough cancer pain (BTCP) in opioid-tolerant patients. This analysis evaluated the correlation between the dose of around-the-clock (ATC) opioid for persistent pain and effective dose of fentanyl sublingual spray for BTCP during the 26-day open-label portion of a phase 3, randomized, placebo-controlled trial. Adult opioid-tolerant patients with 1-4 episodes of BTCP were titrated to a dose of sublingual fentanyl spray (100, 200, 400, 600, 800, 1200, or 1600 mcg) that provided effective analgesia for 2 consecutive BTCP episodes. Of the 130 patients who received fentanyl sublingual spray, 98 (75.4%) completed the titration period. For those achieving successful titration , opioids used for ATC pain management at baseline included oxycodone/oxycodone hydrochloride (75.8%), morphine/morphine sulfate (41.1%), fentanyl/fentanyl citrate (40.0%), hydrocodone/hydrocodone acetaminophen (32.6%), hydromorphone/hydromorphone hydrochloride (31.6%), and methadone/methadone hydrochloride (13.7%). For BTCP, 93.5% (n=86) of patients reported using only oral opioids at baseline; commonly reported medications included hydromorphone hydrochloride (23%), oxycodone (22%), hydrocodone/acetaminophen (22%), and oxycodone/acetaminophen (16%). During the open-label phase, the median morphine equivalent dose of ATC opioid was 200.0 mg (range, 60.0-7545.0 mg). The median dose of fentanyl sublingual spray was 800 mcg and the most common doses were 800 mcg (24.5%) and 1200 mcg (20.4%). Based on the Spearman rank correlation, there was no clinical correlation observed between the successful dose of fentanyl sublingual spray for BTCP and ATC morphine equivalent dose (r=0.351, n=98). The lack of apparent correlation between ATC and BTCP dose underscores the importance of individual patient titration when determining an effective dose of fentanyl sublingual spray for BTCP. Technical editorial andmedical writing assistance provided by Synchrony Medical Communications, LLC, funded by INSYS Therapeutics.