LBA61 - Conventional oral morphine vs. IV patient-controlled analgesia (IPCA) with either hydromorphone (HM) continuous infusion plus rescue dose (CIRD) or HM bolus-only (BO) for severe cancer pain: A randomized phase III study

Background

In a phase II study (Lin, JNCCN 2022) IPCA with HM CIRD or HM BO was superior to oral extended-release (ER) morphine around the clock (ATC) plus immediate-release (IR) morphine rescue dose in patients with severe cancer pain (≥7 at rest on the 11-point Numeric Rating Scale [NRS]). Although efficacy was comparable between CIRD and BO, the sample size was insufficient to test noninferiority. This phase III study validates preliminary findings in a larger cohort.

Methods

A 6-day, open-label, randomized controlled trial was conducted at 48 sites in China. Eligible subjects aged 18 to 80 years diagnosed with a malignant solid tumor and experiencing severe pain were enrolled. After successful opioid titration subjects were randomly assigned (2:2:1 ratio) to one of three arms: (A1) IPCA HM with BO as needed (PRN); (A2) IPCA HM with CIRD; or (B) oral ER morphine plus IR morphine. The primary outcome was average NRS score over Days 1-3 (3DNRS, sum of previous 24-hour average scores Days 1–3 divided by 3).

Results

A total of 1,349 subjects underwent randomization: 542, Arm A1; 540, Arm A2; and 267, Arm B. The mean of 3DNRS (SD) was significantly lower in Arm A1 (2.36 [0.89], P_superiority <0.001) and in Arm A2 (2.26 [0.87], P_superiority <0.001) compared to Arm B (2.94 [1.16]). The mean difference in 3DNRS between Arms A1 and A2 was 0.10 (95% CI, -0.01, 0.20). The upper limit of the 95% CI is significantly less than the predefined noninferiority margin of 0.3 (P_{noninferiority} <0.001). Daily NRS score and subject satisfaction scores on Days 3 and 6 were not significantly different between Arms A1 and A2, but that they were better than in Arm B. The daily equivalent morphine consumption was highest in Arm B, followed by Arm A2, and was lowest in Arm A1. Opioid-related adverse events were significantly more frequent in Arm B compared to Arms A1 and A2.

Conclusions

IPCA HM with or without continuous infusion offers superior pain control compared to conventional oral morphine for management of severe cancer pain. Furthermore, IPCA HM with BO demonstrates non-inferiority to CIRD, suggesting that a PRN approach with IPCA is an effective option to manage severe cancer pain.

Clinical trial identification

NCT04785768.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Fujian Cancer Hospital; Department of Science and Technology of Fujian Province.

Disclosure

All authors have declared no conflicts of interest.