Analgesic efficacy in women and men with cancer pain, treated with strong opioids: are there differences?

Objectives To evaluate sex differences in baseline clinical characteristics, analgesic response, safety profiles and treatment variations among cancer patients initiating WHO step III opioid therapy. Methods and analysis This post hoc analysis used data from a four-arm, multicentre, randomised, comparative, superiority phase IV trial in cancer patients with moderate-to-severe pain requiring WHO step III opioids. The study was conducted across 44 specialist palliative care centres in Italy. Overall, 498 patients were evaluated, including 277 men (55.6%) and 221 women (44.4%). Eligible participants had locally advanced or metastatic tumours and persistent moderate-to-severe pain. Patients were centrally randomised (1:1:1:1) to morphine, oxycodone, buprenorphine or fentanyl around the clock. Follow-up lasted 28 days, with assessments on days 1 day, 3 days, 7 days, 14 days, 21 days and 28 days. Physicians could adjust opioid doses, add adjuvants or switch opioids as clinically indicated. Adverse drug reactions (ADRs) were recorded. Baseline assessments included oncological history, comorbidities, Karnofsky performance status and self-reported psychological status. Pain intensity (PI) was measured on a 0–10 Numerical Rating Scale for average PI (API) and worst pain over the previous 24 hours at each visit. Analgesic response was classified per Farrar’s criteria as non-responders (no improvement or worsening), poor responders (<30% PI reduction) or responders (≥30% reduction). Responders with final API ≤4 were also classified as responders per Corli’s criteria; others were non-responders. Statistical analyses included χ 2 and Fisher’s exact tests, t-tests, Mann-Whitney tests, linear mixed models and logistic regression. Results PI did not differ significantly between sexes. However, in the fentanyl group, dose increased over time differently between sexes (sex-by-time interaction: p=0.0026). Opioid switching from buprenorphine was more often due to inadequate pain control in men, and due to uncontrollable ADRs in women. Among patients with colorectal cancer, women showed greater pain reduction of the worst pain according to Farrar’s criteria (91.3% vs 61.8%, p=0.022). ADRs incidence was higher in women than in men for transdermal buprenorphine (93.2% vs 77.9%, p=0.016). Higher baseline emotional tension was negatively associated with analgesic response (OR 0.64, 95% CI 0.41 to 1.00). Other efficacy and safety outcomes were not statistically significant. Conclusions Overall pain reduction did not differ by sex; however, men and women exhibited distinct patterns in dose escalation, opioid switching and ADR profiles. Accounting for sex differences may support more tailored and effective opioid selection in cancer pain management. Trial registration number NCT01809106 .