A Prospective Observational Study of Anamorelin During Chemoimmunotherapy in Non-Small Cell Lung Cancer With Cachexia (SPIRAL-ANA)

Background: The prognosis of patients with advanced non-small cell lung cancer (NSCLC) complicated by cancer cachexia remains poor. Anamorelin, a ghrelin receptor agonist, has been approved only in Japan for the treatment of cancer cachexia. Methods: This prospective multicentre observational study was conducted to evaluate the impact of anamorelin administration on the efficacy and safety of chemoimmunotherapy in patients with NSCLC and cancer cachexia. The primary endpoint was progression-free survival (PFS), evaluated against a predefined threshold derived from a previous retrospective cohort of patients with cachectic NSCLC treated with chemoimmunotherapy alone. This study was registered in the Japan Registry of Clinical Trials (jRCT1071210053). Results: Between August 2021 and January 2024, 123 patients were enrolled from 29 institutions in Japan, with 114 included in the full analysis set. The median age was 73 years; 28 (24.6%) were female and 20 patients (17.5%) had a performance status of 2. The objective response rate was 57.9% (95% confidence interval [CI]: 48.7%–66.6%). Median PFS and overall survival (OS) were 6.2 months (95% CI: 4.6–7.7) and 18.5 months (95% CI: 13.1–28.6), respectively. The lower limit of the 95% CI for PFS did not exceed the predefined threshold of 5 months. At week 12, 61 of 85 patients (71.8%) had transitioned from cancer cachexia to a non-cachectic state. Landmark survival analyses at week 12 showed that patients who achieved this transition had significantly longer OS compared with those who remained cachectic (19.9 vs. 7.1 months; hazard ratio for cachexia vs. transition, 2.19; 95% CI: 1.19–4.02; p = 0.0098). Grade ≥ 3 hyperglycemia was observed in six patients (5.1%), but no new safety signals were identified. Conclusions: Anamorelin combined with chemoimmunotherapy did not prolong PFS in advanced NSCLC with cancer cachexia, but achieved a high rate of cachexia reversal. Transition to a non-cachectic state was associated with improved OS, suggesting that cachexia reversal may serve as a surrogate for survival benefit. Trial Registration: jRCT1071210053 (jRCT).