Naloxegol, an Oral Peripherally Acting Opioid Receptor Antagonist, Administered Concurrently with First-Line Systemic...

Area of Science:

• Oncology
• Pharmacology
• Clinical Trials

Background:

• Peripheral mu opioid receptors (MORs) contribute to opioid-related side effects impacting quality of life and potentially cancer progression.
• Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation.
• The safety and efficacy of naloxegol in conjunction with systemic cancer therapy remain unevaluated.

Purpose of the Study:

• To assess the safety and efficacy of naloxegol in patients with advanced lung adenocarcinoma receiving first-line systemic therapy.
• To evaluate naloxegol's impact on health-related quality of life (HRQoL) and patient-reported outcomes (PROs).

Main Methods:

• A randomized, double-blind, placebo-controlled trial was conducted.
• The study enrolled 50 patients with advanced lung adenocarcinoma starting first-line systemic therapy.
• The trial was terminated early due to slow patient accrual and PRO completion rates.

Main Results:

• While feasibility endpoints were not fully met, naloxegol showed a signal for improved emotional well-being (FACT-L, p=0.0113) and trends towards better Trial Outcome Index and physical well-being.
• Naloxegol significantly improved constipation, rectal pain during defecation, and abdominal pain associated with constipation.
• Adverse events, urinary hesitancy, pain scores, and survival outcomes were comparable between naloxegol and placebo groups.

Conclusions:

• Naloxegol demonstrates a favorable safety and tolerability profile in this patient population.
• There is a potential benefit of naloxegol in enhancing emotional well-being and HRQoL for lung cancer patients undergoing systemic therapy.
• Larger studies are required to confirm these findings and the previously unappreciated benefits of naloxegol.