Although improving cancer cachexia may enhance patients’ quality of life and treatment tolerance, there is not sufficient evidence regarding its direct effect on life prognosis [24]. There are concerns about past reports on the efficacy of anamorelin, as they possibly included patients with refractory cancer cachexia, thereby inadequately assessing its efficacy. The present study investigated whether the changes in NLR during anamorelin therapy could be useful in predicting treatment efficacy and prognosis, focusing specifically on patients with reversible cancer cachexia. NLR, an inflammatory biomarker, is closely associated with cancer progression, with an NLR of < 5 being shown to be useful in evaluating treatment efficacy and prognosis in patients with cancer [21–23]. To assess its association with treatment efficacy, we compared the changes in NLR before and 4 weeks after treatment initiation. Our results showed a significant decrease in NLR after 4 weeks of anamorelin treatment in patients with NLR of < 5, along with prolonged survival. Conversely, patients with an NLR ≥ 5 showed an increase in NLR after treatment initiation, with no extension in survival observed. These results suggest that changes in NLR following anamorelin administration may indicate treatment efficacy. Furthermore, comparing the data between patients with NLR of < 5 and those with NLR of ≥ 5 before anamorelin administration revealed no significant difference in the change in NLR and survival duration, indicating the importance of monitoring the NLR changes posttreatment to predict treatment efficacy. Our findings support anamorelin therapy as a promising treatment for cancer cachexia and suggest that changes to NLR < 5 during treatment may be useful in predicting treatment efficacy.
However, the observed effects of pretreatment NLR values on pre- and post-treatment NLR changes and survival suggest the importance of establishing an appropriate cutoff value for NLR at treatment initiation. Our study demonstrated that a cutoff value of 4.4 may predict an NLR of < 5 at 4 weeks after anamorelin administration. In other words, patients with NLR < 4.4 before treatment initiation are more likely to have NLR < 5 after anamorelin treatment, suggesting that NLR is a useful prognostic marker for survival outcomes.
Although, this study suggests the potential association of NLR with the therapeutic effects of anamorelin, there are several factors involved in treatment outcomes and survival periods, making their relationship complex. It is possibly difficult to predict these factors sufficiently using only single biochemical parameters. Logistic regression analysis did not show a significant association between albumin and lymphocytes and NLR < 5 after anamorelin administration. At present, albumin is recognized as inflammatory markers; under inflammation, albumin production may decrease due to low liver synthesis function and high capillary permeability [25, 26]. Additionally, lymphocytes may cause excessive activation of the immune system during chronic inflammation, resulting in lymphocyte depletion [27, 28]. Therefore, while these biochemical inflammatory parameters are important indicators for evaluating treatment effects and prognosis, comprehensive research is required to completely understand their significance.
There are several limitations to this study. This was a single-center, retrospective study, and the specific characteristics of the cancer treatment modality and outcomes at the institution should be considered. Additionally, the study population consisted of patients with four cancer types: pancreatic, nonsmall-cell lung, gastric, and colorectal cancers. Since there may be significant variations in survival duration based on cancer type and stage, detailed analyses are necessary for each cancer type. Herein, the limited cases for each cancer type suggest the need for further clinical trials and multicenter collaborative studies. Although this study focused on patients with reversible cancer cachexia, the potential for recovery with anamorelin treatment remains even in cases of refractory cancer cachexia. Therefore, further investigation into the effects of anamorelin in patients with irreversible cachexia is warranted.
In conclusion, NLR changing to < 5 after anamorelin treatment is important for predicting treatment efficacy and survival duration. Specifically, patients with NLR < 4.4 before treatment initiation potentially achieve NLR < 5 after anamorelin treatment, suggesting the utility of NLR as a prognostic marker for survival duration. Therefore, considering changes in NLR before and after treatment initiation is crucial for appropriately predicting the effects and managing anamorelin treatment. The results of this retrospective study highlight the need for prospective comparative trials.