E0263 - Naloxegol and Naldemedine in the Treatment of Persistent Opioid-Induced Constipation (OIC) in Patients With Cancer Pain: A Systematic Review

Tuesday, October 25, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Mounica Vorla, MD

University of Louisville
Louisville, KY

Mounica Vorla, MD¹, Usman Akbar, MD², Maurish Fatima, ³, Sruthi Sekaran, MD⁴, Pooja Roy, MD⁵, Priyanka Pulipaka, MD⁶, Syeda Jeoffrey, MD⁷, Sudeep Yadav, MD¹, Aditya Bamboria, MD¹, Zubair Khan, MD⁸
¹University of Louisville, Louisville, KY; ²NorthShore University Hospital, New York, NY; ³King Edward Medical University, Lahore, Punjab, Pakistan; ⁴Mercy Catholic Medical Center, Philadelphia, PA; ⁵Harlem Hospital Center, New York, NY; ⁶Hackensack Meridian Health - Palisades Medical Center, North Bergen, NJ; ⁷Yale University School of Medicine, New Haven, CT; ⁸UTHealth Houston, Houston, TX

Introduction: Opioid-induced Constipation (OIC) has been a major cause of distress in patients treated with opioids for cancer pain. Numerous drugs have been studied so far to manage refractory OIC. Naloxegol (NKTR-118), a pegylated form of naloxone, and Naldemedine, a peripherally acting μ-opioid receptor antagonist (PAMORA), have shown to alleviate OIC without affecting central analgesia. We study here the efficacy and safety of Naloxegol and Naldemedine in the treatment of OIC - both in clinical trials and in real-world clinical practice.

Methods: We searched and screened a total of 397 articles from databases such as PubMed, Cochrane, Embase, and Web of Science. A total of 9 studies assessing the use of Naloxegol and Naldemedine in patients with cancer pain were included in our review. We extracted data related to response rate and adverse events. Patient assessment of constipation symptoms (PAC-SYM) and assessment of constipation quality of life (PAC-QOL) scales were also analyzed. STATA version 3.2 was used for data analysis.

Results: Of the 397 studies that were identified by our database search, 9 studies were found to be relevant and met the inclusion criteria. Five studies (three RCT and 2 observational), and four observational studies were included for the assessment of Naldemedine and Naloxegol efficacy respectively. A total of 953 OIC cancer patients were treated with Naldemedine, and the response rate for Spontaneous Bowel Movements (SBM) is 72 % (95 % CI, p = 0.004). A significant improvement in Quality-of-life scales such as PAC-SYM and PAC-QOL was also reported. A total of 570 patients from four observational studies treated with Naloxegol were included in our review. In all these studies there was a significant improvement in Bowel Function and Quality of Life after adding Naloxegol despite the poor performance status of the participant. The most common adverse events leading to drug discontinuation were diarrhea, and abdominal pain, dysesthesia.

Discussion: Our results suggest that Naloxegol and Naldemedine are safe and effective in the treatment of refractory OIC in cancer patients. This review is significant in terms of that it includes data from both clinical trials and observational studies. The lack of a control group and a placebo arm in Naloxegol studies warrants more research. However, the randomized control trials employing Naldemedine had an efficacious and safer profile than placebo which is promising in the treatment of OIC with cancer pain.

Author & Year	Type of Study	Participants assessed for efficacy (n)	Male n (%)	Follow up period	Spontaneous bowel movements responder RATES (%)	Any Adverse effects N (%)
Naldemedine
Katakami, 2017	Phase IIb RCT	225, Nal- 169, P- 56	Nal- 100 (69%), P- 34 (60%)	2 weeks	Nal- 122 (72%), P- 21 (37.5%)	Nal- 120 (71%), P- 29 (52%)
Katakami, 2017	Phase III RCT	193, Nal- 97, P- 96	Nal- 59 (61%), P- 60 (62.5%)	2 weeks	Nal- 69 (71%), P- 33 (34%)	Nal- 43 (44%), P- 25 (26%)
Katakami 2017	Open-label extension study	Nal- 131	Nal- 74 (56.5%)	12 weeks	NA	Nal- 105 (80%)
Hiruta, 2021	Multi-center Retrospective study	255	Nal- 179 (60.5%)	NA	Nal- 235 (79%)	204 (69%)
Nishiba, 2022	Multi-center Retrospective study	149	Nal- 89 (60%)	NA	Nal- 98 (66%)	116 (78%)
Naloxegol
Cobo Dols, 2021	Prospective study	126	74(59%)	12 m	98/126 (77.8%	19 (15%)
Lemaire, 2021	Non interventional follow-up study	124	117 (63.2%)	1 m	79 (73.4%)	43 (32.8%)
Ostan, 2021	Observational study	150	77(51.3%)	1 m	NA	51 (33%)
Davies, 2022	Observational study	170, assessed for efficacy- 143, assessed for safety- 170 Group I- 76, Group II- 98	65 (45%)	1 m	Group I 55(72%), Group II 74(75.5%)	89/170 (52.4%)

Table: N= number, Nal= Naldemedine, P= Placebo, NA= Not Applicable.

Disclosures:

Mounica Vorla indicated no relevant financial relationships.

Usman Akbar indicated no relevant financial relationships.

Maurish Fatima indicated no relevant financial relationships.

Sruthi Sekaran indicated no relevant financial relationships.

Pooja Roy indicated no relevant financial relationships.

Priyanka Pulipaka indicated no relevant financial relationships.

Syeda Jeoffrey indicated no relevant financial relationships.

Sudeep Yadav indicated no relevant financial relationships.

Aditya Bamboria indicated no relevant financial relationships.

Zubair Khan indicated no relevant financial relationships.

Mounica Vorla, MD¹, Usman Akbar, MD², Maurish Fatima, ³, Sruthi Sekaran, MD⁴, Pooja Roy, MD⁵, Priyanka Pulipaka, MD⁶, Syeda Jeoffrey, MD⁷, Sudeep Yadav, MD¹, Aditya Bamboria, MD¹, Zubair Khan, MD⁸. E0263 - Naloxegol and Naldemedine in the Treatment of Persistent Opioid-Induced Constipation (OIC) in Patients With Cancer Pain: A Systematic Review, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.