Intravenous PCA with hydromorphone outperforms oral morphine for severe cancer pain

In the management of severe cancer pain, intravenous patient-controlled analgesia (PCA) with hydromorphone delivers superior pain control with greater patient satisfaction as compared with conventional oral morphine, according to the phase III open-label SYLT-021 study.

More importantly, as-needed bolus-only hydromorphone dose demonstrates noninferiority to continuous hydromorphone infusion with rescue dose in opioid-naïve patients, with less equivalent morphine consumption during the entire 6 days of treatment.

The three-arm SYLT-021 met its primary endpoint, with the average Numeric Rating Scale (NRS) pain score over treatment days 1–3 being significantly lower in the hydromorphone bolus-only and hydromorphone continuous infusion arms than in the oral extended-release plus immediate-release morphine arm (bolus vs oral: mean difference, 0.58, 95 percent confidence interval [CI], 0.42–0.74; p<0.001 for superiority; continuous infusion vs oral: mean difference, 0.68, 95 percent CI, 0.52–0.84; p<0.001 for superiority), reported lead study author Dr Rongbo Lin from Fujian Cancer Hospital in Fuzhou, China. [ESMO 2024, abstract LBA61]

Comparing the two intravenous hydromorphone PCA arms, bolus-only compared favourably with continuous infusion (mean difference, 0.10, 95 percent CI, –0.01 to 0.20; p<0.001 for noninferiority).

The results were consistent in the subgroups of opioid-naïve and opioid-tolerant patients, with intravenous PCA with hydromorphone, regardless of dosing, showing superiority over oral morphine (p<0.001 for all), Lin noted.

However, between the two hydromorphone arms, the noninferiority of bolus-only dosing vs continuous infusion was observed only in the opioid-naïve subgroup (mean difference, 0.07, 95 percent CI, –0.06 to 0.19; p<0.001) and not in the opioid-tolerant subgroup (mean difference, 0.16, 95 percent CI, –0.01 to 0.34; p<0.065 for noninferiority), he added.

Other endpoints such as daily NRS score and patient satisfaction scores on days 3 and 6 did not significantly differ between the bolus-only and continuous infusion hydromorphone arms, although they were better than in the oral morphine arm. From treatment days 1 through 6, the daily equivalent morphine consumption was high in the oral morphine arm, low in the continuous infusion arm, and lower in the bolus-only arm.

As for opioid-related adverse events, “all were grade 1/2 [in severity] and were significantly more frequent in the oral arm [33.71 percent] than in the bolus-only and continuous infusion arms [20.11 percent and 22.96 percent, respectively],” Lin said.

Constipation, nausea, vomiting, and dizziness were the most common opioid-related adverse events.

“Maintaining analgesia for persistent cancer pain with conventional oral extended-release morphine around the clock as a background dose plus immediate-release morphine as a rescue dose for breakthrough cancer pain is widely accepted,” Lin pointed out. [NCCN Guidelines. Adult Cancer Pain, version 2.2024]

SYLT-021 aims to fill a gap in the evidence base regarding alternative analgesic dosing routes and administration schedules in cancer pain management, he added.

The findings validate those of the preceding phase II study and suggest that an as-needed approach with intravenous PCA with hydromorphone is an effective option to manage severe cancer pain, especially for opioid-naïve patients, Lin concluded. [J Natl Compr Canc Netw 2022;20:1013-1021.e3]

In SYLT-021, a total of 1,349 adult patients who had a malignant solid tumour and were experiencing severe pain (≥7 on the 11-point NRS at rest) had been randomly assigned to receive 6 days of treatment with intravenous PCA with hydromorphone bolus-only as-needed (n=542, median age 60 years, 56.46 percent male), intravenous PCA with hydromorphone continuous infusion with rescue dose (n=540, median age 62 years, 64.07 percent male), or oral extended-release plus immediate-release morphine (n=267, median age 60 years, 59.93 percent male).