Endocrine immune-related adverse event is a prognostic biomarker independent of lead-time bias.

OBJECTIVES: Immune-related adverse events (irAEs) are known to be associated with clinical efficacy and better prognoses in patients receiving immune checkpoint inhibitors. In particular, endocrine irAE (e-irAE) is related to better prognoses. Since the incidence of irAEs increase as treatment duration becomes longer, we should consider lead-time bias not to overvalue the result. We evaluated the impact of e-irAE on the outcome before and after 6-, 9-, and 12-week landmark analyses. MATERIALS AND METHODS: We evaluated 222 patients with advanced or recurrent non-small cell lung cancer who received anti-PD-1 antibodies such as nivolumab or pembrolizumab from January 2016 to April 2021. Treatment efficacy and outcomes of patients with or without e-irAE (e-irAE group or no e-irAE group) were retrospectively evaluated. In addition, we performed 6-, 9-, and 12-week landmark analyses to exclude the effect of lead-time bias. RESULTS: Median progression free survival (PFS) was significantly longer in the e-irAE group than in the no e-irAE group (overall: 15.3 vs 3.9 months, p < 0.0001; 6-week: 15.3 vs 4.9 months, p < 0.0002; 9-week: 19.8 vs 6.1 months, p = 0.0012, 12-week: 19.8 vs 8.4 months, p = 0.017). Overall survival (OS) was significantly longer in the e-irAE group (overall: not reached (NR) vs 15.4 months, p = 0.0003; 6-week: NR vs 19.1 months, p = 0.0049, 9-week: NR vs 22.2 months, p = 0.006; 12-week: NR vs 23.3 months, p = 0.04). We used the multivariate cox proportional hazard model to adjust for confounding factors and found that e-irAE had better impact on both PFS and OS (PFS: overall: hazard ratio 0.37 [95% confidence interval 0.23-0.56], 6-week: 0.41 [0.26-0.63], 9-week: 0.43 [0.24-0.63], 12-week: 0.52 [0.31-0.84]; OS: overall: 0.40 [0.22-0.68], 6-week: 0.46 [0.25-0.79], 9-week: 0.47 [0.24-0.84], 12-week: 0.58 [0.29-1.08]). CONCLUSION: The occurrence of endocrine irAE was associated with better efficacy and prognoses regardless of the lead-time bias.

[Retracted] Predictors of efficacy of anamorelin in patients with non­small cell lung cancer and cachexia: A retrospective study.

[This retracts the article DOI: 10.3892/ol.2023.14154.].

Predictors of efficacy of anamorelin in patients with non­small cell lung cancer and cachexia: A retrospective study.

Anamorelin, a ghrelin receptor agonist, is approved in Japan for the treatment of cachexia in patients with lung and gastrointestinal cancer. However, there is limited research on the usefulness of anamorelin in clinical settings, therefore, the present study evaluated its efficacy using patient characteristics. A total of 40 patients with non-small cell lung cancer and cachexia who were prescribed anamorelin in the Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine (Aomori, Japan) between July 2021 and November 2022, were retrospectively assessed. Anamorelin was prescribed at a dose of 100 mg once daily to patients who had lost >5% of their body weight within 6 months. All patients were weighed before treatment and those who continued anamorelin treatment for 12 weeks were also weighed at 12 weeks. A logistic regression analysis was used to analyze the association between background characteristics and early discontinuation of treatment with anamorelin (within 4 weeks). The median age was 67 years (range, 36-88), and 65% of the patients were male. There were 24 patients (60.0%) with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score 1, 11 patients (27.5%) with an ECOG-PS score 2 and five patients (12.5%) with an ECOG-PS score 3. The early discontinuation group included 11 patients (27.5%). An ECOG-PS score ≥2 (odds ratio, 7.85; 95% confidence interval, 1.43-43.21; P=0.018) was associated with early discontinuation. A total of 18/40 patients (45.0%) were able to continue anamorelin treatment for 12 weeks, and the mean change in body weight was +2.31 kg, which was a significant change from the weight recorded at baseline (P=0.027). The mean changes in lean body mass and soft lean mass between baseline and 12 weeks were +1.97 kg (P=0.14) and +1.26 kg (P=0.15), respectively. The results from the present study indicate that anamorelin is unlikely to be useful for patients with a poor general condition (ECOG-PS score ≥2).