DISCUSSION
NSCLC, cancer, weight gain, LBM gain, cancer cachexia
CANCER, NSCLC, ADVERSE DRUG REACTION
We performed analyses of the ONO‐7643‐04 study to evaluate the efficacy and safety of anamorelin in subgroups. In terms of its efficacy, we found greater improvements in LBM, body weight, and appetite with anamorelin than with placebo for nearly all the analyzed subgroups. Overall, these results suggest that the efficacy of anamorelin is unaffected by most patient characteristics. Furthermore, anamorelin may have benefits in terms of LBM gain, weight gain, and improved appetite regardless of the patient's nutrition‐related biomarkers at baseline, including C‐reactive protein, albumin, and hemoglobin.The results regarding the LBM change in the subgroups in our study are generally similar to those in the international ROMANA‐1 and ROMANA‐2 studies.The changes in appetite scores from baseline to week 12 were greater with anamorelin than with placebo in most subgroups of patients, although the difference between the anamorelin and placebo groups was attenuated in the following subgroups: female, low BMI, PS 2, no concomitant chemotherapy, concomitant chemotherapy with EGFR‐TKI, and history of two prior chemotherapy regimens (Figure The ORs for LBM and body weight responder rates tended to be greater in patients with low BMI at baseline than in patients with higher BMI (Figure Regarding the appetite responder rate, the OR tended to be greater in patients with PS 2 than in those with ECOG PS 0–1 (Figure Adverse drug reactions are of particular concern in elderly patients or those with poor general condition. Notably, the incidences of cardiac conduction disorders and blood glucose‐related disorders, which were more frequent in anamorelin‐treated patients,Limitations of this study include its design and setting as a controlled clinical trial with strict eligibility criteria. Thus, the results may not fully represent its use in actual clinical practice. The study excluded patients with PS ≥3. Therefore, we could not evaluate the efficacy or safety of anamorelin in these patients. Some subgroups had small numbers of patients with high variability, and no adjustment was made for multiple comparisons. These factors may limit the robustness of the statistical analyses and raise the possibility of type II error. In addition, we used different methods to measure body weight (scales) and LBM (DEXA), which may contribute to the differing gains in body weight and LBM. Furthermore, the QOL‐ACD has not been sufficiently validated for the assessment of appetite, and no minimal important difference has been set. In international studies, the Functional Assessment of Anorexia/Cachexia Treatment, which consists of multiple items, was used to assess appetite. In the present study, we evaluated appetite using a single question (item 8 of QOL‐ACD). This item was used in the previous clinical trials of anamorelin in Japan with consistent results among the trials.In conclusion, we observed greater improvements in LBM, body weight, and appetite, together with higher responder rates, in anamorelin‐treated patients compared with placebo‐treated patients in nearly all subgroups analyzed in this study of patients with NSCLC and cancer cachexia. We also found that anamorelin is tolerable regardless of age or PS. Taken together, these results suggest that anamorelin has a beneficial impact on cancer treatment by maintaining and improving the condition of cancer patients through improvements in body weight and appetite that are regardless of patient characteristics.