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Desensitizing Effect of Cancer Cachexia on Immune Checkpoint Inhibitors in Patients With Advanced NSCLC
Taichi Miyawaki1,2, Tateaki Naito1, Akihro Kodama1
1Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
Introduction:
Programmed cell death 1 (PD-1) inhibitors have become standard treatment for patients with advanced NSCLC. However, few studies have focused on the impact of cancer cachexia on the efficacy of PD-1 or programmed death-ligand 1 (PD-L1) inhibitors among patients with NSCLC.
Methods:
We retrospectively reviewed medical records of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy from May 2016 to December 2018. We defined cancer cachexia as unintentional weight loss greater than 5% over 6 months and high PD-L1 as greater than 50% expression on tumor cells. We evaluated the objective response rates (ORRs) and progression-free survival (PFS).
Results:
Among 108 patients, 52 had cancer cachexia. Patients with cachexia had a lower ORR (15% versus 57%, p < 0.001) and shorter PFS (2.3 mo versus 12.0 mo, p < 0.001) than those without cachexia. Patients with low PD-L1 expression had a lower ORR (14% versus 53%, p < 0.001) and shorter PFS (2.8 mo versus 10.8 mo, p = 0.002) than those with high PD-L1 expression. Multivariate analysis revealed cancer cachexia and low PD-L1 expression as independent negative predictors of PFS. Among patients with cachexia, there was no significant difference in the ORR (p = 0.514) or PFS (p = 0.992) on the basis of PD-L1 expression.
Conclusions:
Our findings indicate that cancer cachexia might be a negative predictor of the efficacy of PD-1 or PD-L1 inhibitors and reduce the impact of PD-L1 expression on the effect of PD-1 or PD-L1 inhibitors in patients with advanced NSCLC. Further clinical and basic studies are needed.
Insights
Cancer cachexia significantly reduces the effectiveness of PD-1/PD-L1 inhibitors in advanced NSCLC patients. Cachexia diminishes the impact of PD-L1 expression on treatment outcomes.
Area of Science:
- Oncology
- Immunotherapy
Background:
- Programmed cell death 1 (PD-1) inhibitors are standard for advanced non-small cell lung cancer (NSCLC).
- The influence of cancer cachexia on PD-1/PD-L1 inhibitor efficacy in NSCLC remains understudied.
Purpose of the Study:
- To investigate the impact of cancer cachexia on the efficacy of PD-1 or PD-L1 inhibitors in advanced NSCLC patients.
- To evaluate the association between cancer cachexia, PD-L1 expression, and treatment outcomes.
Main Methods:
- Retrospective review of 108 advanced NSCLC patients receiving PD-1/PD-L1 inhibitor monotherapy.
- Cancer cachexia defined as >5% unintentional weight loss over 6 months; high PD-L1 as >50% tumor cell expression.
- Evaluation of objective response rates (ORRs) and progression-free survival (PFS).
Main Results:
- Patients with cachexia had significantly lower ORR (15% vs. 57%) and shorter PFS (2.3 vs. 12.0 months).
- Low PD-L1 expression was also associated with lower ORR (14% vs. 53%) and shorter PFS (2.8 vs. 10.8 months).
- Cancer cachexia and low PD-L1 expression were independent negative predictors of PFS.
Conclusions:
- Cancer cachexia negatively predicts the efficacy of PD-1/PD-L1 inhibitors in advanced NSCLC.
- Cachexia may attenuate the impact of PD-L1 expression on treatment outcomes.
- Further clinical and basic research is warranted.
