Phase III trials of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia (ROMANA 1 and 2).

9500 Background: Patients with advanced cancers frequently experience anorexia and cachexia, which is associated with decreased functional status and poor tolerance of chemotherapy. ROMANA 1 and 2 were two randomized, double blind trials evaluating the effect of anamorelin, a ghrelin receptor agonist, on cachexia in patients with advanced NSCLC. Methods: We randomly assigned 484 patients (ROMANA 1) and 495 patients (ROMANA 2) with inoperable stage III or stage IV NSCLC and cachexia ( ≥ 5% weight loss within prior 6 months or BMI < 20 kg/m2) to placebo or anamorelin 100 mg orally once daily. Co-primary efficacy endpoints were the change in lean body mass and handgrip strength from baseline over 12 weeks. Secondary endpoints included change in body weight and symptom burden over 12 weeks and pooled survival from ROMANA 1 and ROMANA 2. Exploratory analyses evaluated change in total body mass and fat mass from baseline to 12 weeks. Results: Patients assigned to anamorelin experienced an increase in lean body mass compared to those assigned to placebo in ROMANA 1 (1.10 vs -0.44 kg, p < 0.001) and ROMANA 2 (0.75 vs -0.96 kg, p < 0.001), but no difference in handgrip strength. Patients assigned to anamorelin also had a significant increase in body weight (2.2 vs 0.14 kg, p < 0.001) and (0.95 vs -0.57 kg, p < 0.001) and improvement in their anorexia/cachexia symptoms (4.12 vs 1.92, p < 0.001) and (3.48 vs 1.34, p = 0.002) in ROMANA 1 and 2, respectively. Exploratory analysis demonstrated an increase in total body mass (2.87 vs 0.07 kg, p < 0.001) and (2.04 vs -0.59 kg, p < 0.001), and fat mass (1.21 vs -0.13 kg, p < 0.001) and (0.77 vs 0.09 kg, p = 0.012) for anamorelin versus placebo in the two studies, respectively. Anamorelin was well tolerated with hyperglycemia and diabetes as the most frequent drug-related adverse events ( ≤ 5%). Median 1-year survival was not different between study arms. Conclusions: Anamorelin increased lean body mass, body weight, total body mass and fat mass indicating anabolic activity and restoration of energy balance in patients with advanced NSCLC. Patients also experienced significant improvement in anorexia/cachexia symptoms. Anamorelin was well tolerated, with similar pooled survival between study arms. Clinical trial information: NCT01387269 and NCT01387282.