Efficacy and safety of lanreotide 120 mg in the treatment of clinical symptoms associated with inoperable malignant intestinal obstruction (IMIO): Results from a phase II multicenter study.

Abstract

4118 Background: Intestinal obstruction is a severe complication in patients (pts) with digestive or gynecological cancers. For inoperable pts, there is a need to relieve symptoms and limit nasogastric tube (NGT) use. Previous studies have suggested the efficacy of somatostatin analogues in relieving obstruction-related symptoms such as nausea, vomiting and pain. Methods: This was a single arm, prospective study (NCT02275338). Pts with IMIO received one deep subcutaneous injection of LAN 120mg at day 0 (D0). Evaluations were performed on D7, 14 and 28. The primary endpoint was the proportion of responders before or at D7. Response was defined as ≤2 vomiting episodes/day (for pts without NGT at baseline) or no vomiting recurrence (after NGT removal), during at least 3 consecutive days at any time point between the D0 and D7. In line with the literature, a proportion of 30% responders was used as reference for defining statistical significance. Responders at D28 were offered a second LAN 120 mg injection. Results: 52 pts with advanced GI or ovarian malignancies were included in 15 Belgian sites. 17 pts without NGT and 35 with NGT. 21 pts received a second dose of LAN. Median age was 68.0 (59.5; 76.0) years. On D7 the proportion of responders in the ITT population was 24/52 (46.2%), significantly greater than the reference proportion of 30% (one-sided binomial test: p = 0.006). Pts without NGT responded better (15/17, 88.2%) than pts with NGT (9/35, 25.7%). Pts without ascites responded better (57.7% vs 34.6%). Pts with NGT showed a steady trend for clinical improvement leading to sustainable responses of 45.7% on D14. Median time to response was 9 days for the overall population; 3 days for patients without NGT vs 14 days for patients with NGT (p < 0.001). The most frequently reported AEs were GI disorders (in 34 pts). The most common events were diarrhoea and abdominal pain. Conclusions: Our study is the first using long acting LAN 120mg in patients with IMIO and suggests an effect in controlling clinical symptoms in pts with and without NGT at baseline. LAN 120 mg safety profile was similar to that reported for the other indications. Clinical trial information: NCT02275338.

The range and suitability of outcome measures used in the assessment of palliative treatment for inoperable malignant bowel obstruction: A systematic review

“…Of the 80 papers included in the review, 12 reported RCTs (2 papers reporting different outcomes for the same RCT), 3 quasi-RCTs, 8 single-arm trials and 57 observational studies with a total of 13,898 participants. For one single-arm trial not yet published, outcomes were extracted from trial results on ClinicalTrials.gov and a published abstract [22] . Study characteristics are summarised in Supplementary File 1.…”

“…Nine studies focused exclusively on patients with colorectal cancers [45,57,60,73,74,77,89,92,93] , nine studies focused on patients with gynaecological cancers [32,37,61,69,79,80,86,87,94] . [22,29] covering the same RCT; 2 Including Hardy et al, 1998 [24] (majority ovarian).…”

“…Adverse events National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) [22,37,65]…”

“…Edmonton Symptom Assessment Scale (ESAS) [22,27,33,91] Rotterdam Symptom Checklist (RSC) [91] World Health Organisation Control of Vomiting scale [25,76,79] Visual Analogue Scale (VAS) using graphic representations of emotive faces for patient to indicate feelings [22,28,31,62,65,81,86,100] Study-specific, customised measurement tool [30,32,34,38,85,90] Table 4 Distribution across COMET domains [21] of the 172 items extracted from PROMs.…”

“…Within 7 days of procedure [58] Within 30 days of procedure [57] Weekly for 4 weeks [38] Weekly at weeks 1, 2, 4, 8, 12 and 24 [85] On admission and at discharge [100] Daily until intestinal transit recovered [83] Daily to day 3, 4, 6 or 7 [23,26,30,32,33,34,35,36,73,76,79,86,88] Day 1, then every 3 days [81] Days 1, 3, 7, then weekly [90] Days 1,7,14,29,57,85 [27] Days 2 and 3 [89] Days 2, 4, 8, 15 [37,65] Days 3 and 6 [31] Days 3, 7, 10, 20 [28] Days 4, 8, 15 [37] Days 7, 14, 28 [22] At 1 week, 1 month and 3 months [91] 3, and were used in four studies [23/29,42,49,85] . Two RCTs [23/29,42] and two observational studies [49,85] chose quality of life as a primary outcome, but did not recruit or retain enough patients at follow up to enable successful analyses.…”