Predictors of therapeutic efficacy of anamorelin in patients with gastric, pancreatic, and colorectal cancer.
Authors: Shimomura Kazuhiro , Ogata Takatsugu , Maeda Akimitsu , Narita Yukiya , Taniguchi Hiroya , Murotani Kenta , Tajika Masahiro , Hara Kazuo , Muro Kei , Uchida Kosaku 
Published: January 2023

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Background: Anamorelin is a highly selective ghrelin receptor agonist that improves appetite and increases lean body mass in patients (pts) with cachexia. We aimed to investigate the predictors of therapeutic efficacy of anamorelin in pts with gastrointestinal cancer. Methods: This retrospective study included pts with gastric cancer (GC), pancreatic cancer (PC), and colorectal cancer (CRC) treated with anamorelin at our institution between May 2021 and July 2022. Glasgow Prognostic Score (GPS) was defined as follows: GPS 0: CRP≤1.0 (mg/dL) and Alb≥3.5 (g/dL), GPS 1: either CRP>1.0 or Alb<3.5, GPS 2: CRP>1.0 and Alb<3.5. The endpoints were the response rate (RR) of anamorelin and time to treatment failure (TTF). RR was defined as the proportion of appetite improvement within 3 weeks of anamorelin, and TTF was defined as the time from the start of anamorelin to discontinuation due to insufficient response. The observation period lasted 12 weeks. RR was analyzed by univariate and multivariate logistic regression analyses, and TTF by competing risk analysis. In the competing analysis, discontinuation of anamorelin due to worse symptoms, hospital transfer for poor condition, and adverse events (AEs) were considered as competing events. Results: A total of 103 pts were included; median age was 70 (range: 37–84) years, 61 pts (59%) were men, and 17 pts (17%) had an ECOG PS ≥2. The proportion of GC/PC/CRC were 43/42/16%; median body mass index (BMI) was 19.9 (range: 14.4–26.8) kg/m2. The treatment line for 1st/2nd/≥3rd/others was 51/13/14/22%, respectively. GPS was 0/1/2 in 21/30/49%, respectively. Except for treatment line, there were no significant differences in patient characteristics according to the cancer type. A total of 12 pts discontinued treatment owing to AEs (nausea, 3; epigastric distress, 2; fatigue, 2; poor physical condition, 2; staggering, 1; pulsation, 1; diarrhea, 1 pts). The RR was 42%. Pts with GPS 2 had less improvement in appetite than those with GPS 0 or 1 (26% vs. 56%, adjusted odds ratio [95% confidence interval (95%CI)]:0.22 [0.07–0.69], p=0.009). The RR of pts with GC, PC, and CRC were 44%, 42%, and 41%, respectively. The cumulative incidence of discontinuation of anamorelin after 12 weeks was higher in pts with GPS 2 than in those with GPS 0 or 1 (46% vs. 30%). The TTF in pts with GPS 2 was significantly shorter than that in pts with a GPS 0 or 1 (adjusted subdistributional hazard ratio [95%CI]:2.80 [1.37–5.72], p=0.005). There was no statistically significant difference in TTF by cancer type, although TTF was shorter in GC and PC than in CRC. Other factors, including age, sex, baseline BMI, ECOG PS, lines of therapy, and cancer type did not correlate with RR and TTF. Conclusions: In pts with a GPS of 0 or 1, anamorelin showed better appetite improvement and a longer treatment effect than in those with GPS 2. TTF was shorter in pts with GC and PC; therefore, the timing of use should be carefully considered.