Effectiveness of naloxegol in patients with cancer pain suffering from opioid-induced constipation

Abstract

Naloxegol, an oral once-daily peripherally acting mu-opioid receptor antagonist, is indicated for the treatment of opioid-induced constipation (OIC) with inadequate response to laxative(s), in cancer and non-cancer patients. This study mainly aimed to assess in real-life conditions the e cacy and safety of naloxegol in cancer pain patients, and the evolution of their quality of life. MethodsA non-interventional, 4-week follow-up study was conducted in 24 French oncology and pain centers between 2018 and 2019. Eligible patients were aged ≥ 18 years, treated with opioids for cancer-pain, and started naloxegol for OIC with inadequate response to laxatives. The rate of the response to naloxegol (primary criterion) was assessed at W4. The evolution of quality of life was measured using the Patient Assessment of Constipation Quality of Life (PAC-QOL). ResultsA total of 124 patients were included (mean age: 62 ± 12 years; ECOG ≤ 2: 79%; primary cancer: lung 18%, breast 16%, prostate 11%, head and neck 9%, digestive 9%...; metastatic stage: 80%). At inclusion, the median opioid dosage was 60 mg of oral-morphine or equivalent. At W4, the response rate was 73.4% (95% CI [63.7%-83.2%]) and 62.9% (95% CI [51.5%-74.2%]) of patients had a clinically relevant change in quality of life (decrease in PAC-QOL score ≥ 0.5 point). Adverse events related to naloxegol were reported in 8% of patients (7% with gastrointestinal events; one serious diarrhea). ConclusionThis real-world study shows that naloxegol is effective and well tolerated in cancer pain patients with OIC and that their quality of life improves under treatment.

A Prospective, Real-World, Multinational Study of Naloxegol for Patients with Cancer Pain Diagnosed with Opioid-Induced Constipation—The NACASY Study

“…Regarding the primary efficacy endpoint, a high proportion of study patients (72.4%) responded to naloxegol treatment during the 4-week study follow-up period. This result is also consistent with the reported percentages from two other similar observational studies with naloxegol, in which the response rate was assessed by the number of BMs over the previous weeks [22,23].…”

“…It is worth mentioning that most of these adverse events frequently occurred within the first two weeks of treatment with naloxegol [ 20 , 22 ]; therefore, it is also possible that most adverse reactions leading to drug discontinuation occur early during treatment. The tolerability profile was consistent with those reported in both clinical trials [ 19 , 20 ] and observational studies [ 22 , 23 ], the most commonly reported naloxegol-emergent adverse events in our study being of gastrointestinal nature and of mild to moderate severity.…”

“…There was a small proportion of subjects who reported adverse reactions due to naloxegol treatment (13.5%), and only 7.1% of the whole safety population discontinued early from the study as a consequence of naloxegol-related adverse events. This proportion is slightly lower than the 10% reported in phase III, 12-week clinical trials [19], and is within the range reported in similar real-world prospective observational studies: 4.8% after 12 months but all of them within the first 4 weeks [22], and 6.8% after 4 weeks [23], respectively. It is worth mentioning that most of these adverse events frequently occurred within the first two weeks of treatment with naloxegol [20,22]; therefore, it is also possible that most adverse reactions leading to drug discontinuation occur early during treatment.…”

“…In a 12-month follow-up observational study (Kyonal Study), Cobo et al showed the sustained efficacy and safety of naloxegol improving OIC, quality of life as measured with the PAC-QOL, and symptoms of cancer patients [ 22 ]. A more recent 4-week follow-up study (MovE Study), conducted in France in patients with cancer and OIC, receiving naloxegol treatment also showed high response rates to naloxegol, with an improvement of constipation that was associated with an improvement of quality of life [ 23 ]. After 4 weeks of treatment with naloxegol, Cobo et al in the Kyonal Study reported a response rate of 74.6% [ 22 ], and Lemaire et al in the MovE Study found a response rate of 73.4% [ 23 ].…”

“…Recently, two single-country real world studies demonstrating the efficacy and safety of naloxegol in cancer patients with OIC have been published [ 22 , 23 ]. However, data regarding the use of naloxegol in this group of patients in daily clinical practice across Europe do not exist.…”