Abstract:
12110 Background: BW loss and anorexia are key clinical manifestations of cancer cachexia, a multifactorial syndrome affecting around 80% of patients (pts) with advanced cancer. BW loss is associated with reduced tolerance and response to cancer therapy, and shorter survival. ANAM is a novel, oral selective ghrelin receptor agonist. In ROMANA 1 and 2 (NCT01387269, NCT01387282) studies in pts with NSCLC and cachexia, ANAM treatment significantly increased BW and improved anorexia symptoms and concerns compared with placebo (PBO), with rapid responses occurring at wk 3 and sustained at wk 6, 9, and 12. In this post-hoc analysis, we report the timing of BW responses to assess the effects of ANAM treatment at and beyond wk 3. Methods: In ROMANA 1 and 2, pts with advanced NSCLC and BMI <20 kg/m2 or BW loss ≥5% in the past 6 mo received ANAM or PBO for 12 wk. BW responses were grouped on the basis of BW change from baseline (BW gain 0 to <5% or ≥5%, and BW loss); pts were classified according to the timing of first BW response as early responders (at wk 3), late responders (at wk 6, 9, or 12), and non-responders. Missing values were not imputed. Categorical variables are presented as number and percentages, with statistical comparisons performed using the chi-square test. Results: In total, 552 pts in the ANAM arm and 277 in PBO were included in the analysis for all time points; at wk 3/6/9/12, data were available for 534/520/461/412 pts in the ANAM arm and 270/262/229/206 in PBO. The non-cumulative rate of pts with BW gain ≥5% was significantly higher with ANAM compared with PBO at wk 3 (13 vs 6%, p=.0030), wk 6 (26 vs 8%, p<.0001), wk 9 (28 vs 9%, p<.0001), and wk 12 (31 vs 11%, p<.0001); conversely, the rate of BW loss was significantly lower with ANAM at all time points (p<.0001). There were no significant differences between ANAM and PBO in the rate of pts with BW gain 0 to <5% at wk 3, 6, 9, and 12 (p≥.0500). The timing of first occurrence of ≥5% BW gain response is shown in the table. The rates of early and late responders were significantly higher with ANAM compared with PBO, with 28% of ANAM-treated pts first responding beyond wk 3; a larger proportion of responses with ANAM were sustained over time. Conclusions: ANAM significantly increased the rates of ≥5% BW gain and reduced BW loss rates compared with PBO at all time points; the proportion of first responders at wk 3 and beyond wk 3 was higher with ANAM, with the most significant increase seen at wk 6. Continuing ANAM treatment beyond wk 3 results in a clinically significant benefit. Clinical trial information: NCT01387269, NCT01387282. [Table: see text]
