Early Detection of Therapeutic Benefit from PD-1/PD-L1 Blockade in Advanced Lung Cancer by Monitoring Cachexia-Related Circulating Cytokines
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Characteristics
2.2. Definition of Cancer Cachexia
2.3. Blood Collection
2.4. Multiplex Analysis
2.5. Therapeutic Efficacy and Survival Analysis
2.6. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Identification of Cachexia-Related Cytokines
3.3. Higher Eotaxin-1 Was Associated with Better Therapeutic Response and Overall Survival
3.4. Cachexia-Related IL-6 Was Associated with Immune-Related Adverse Events
3.5. Higher IL-10 at Baseline and during Treatment Predicted Worse Overall Survival after PD-1/PD-L1 Blockade Therapy
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Feature | N | Percentage (%) |
---|---|---|
Sex | ||
Female | 14 | 25.5 |
Male | 41 | 74.5 |
Age at diagnosis (years) | ||
<60 | 13 | 23.6 |
60~75 | 26 | 47.3 |
≥75 | 16 | 29.1 |
Histology | ||
Adenocarcinoma | 37 | 67.3 |
Squamous carcinoma | 8 | 14.5 |
Others | 10 | 18.2 |
Clinical stage | ||
III | 3 | 5.5 |
IVA | 26 | 47.3 |
IVB | 26 | 47.3 |
ECOG PS | ||
0–1 | 48 | 87.3 |
2 | 7 | 12.7 |
Smoking status | ||
Never | 5 | 9.1 |
Former/Current | 50 | 90.9 |
PD-L1 expression | ||
<50% | 30 | 54.5 |
≥50% | 19 | 34.5 |
NA | 6 | 10.9 |
Line of immunotherapy | ||
First | 39 | 70.9 |
Second | 12 | 21.8 |
≥Third | 4 | 7.3 |
Actionable mutation | ||
(−)/undetected | 49 | 89.1 |
EGFR(+) | 5 | 9.1 |
ROS1(+) | 1 | 1.8 |
Number of metastatic sites | ||
<3 | 43 | 78.2 |
≥3 | 12 | 21.8 |
irAEs | ||
No | 10 | 18.2 |
Grade 1–2 | 26 | 47.3 |
Grade 3–4 | 19 | 34.5 |
Type of immunotherapy | ||
Nivolumab | 2 | 3.6 |
Pembrolizumab | 35 | 63.6 |
Atezolizumab | 18 | 32.7 |
Variables | Total (n = 41) | Cachexia (n = 21) | Non-Cachexia (n = 20) | p-Value |
---|---|---|---|---|
Sex, male/female | 30/11 | 16/5 | 14/6 | 0.734 |
Age at diagnosis (Y), median (Q1, Q3) | 68 (59, 75) | 68 (61, 78) | 68 (58.5, 74.3) | 0.497 |
Weight at baseline, Kg | 61.6 (37.6, 95.6) | 55.9 (37.6, 79.0) | 62.3 (39.2, 95.6) | 0.039 |
Smoking (smoker/no smoker) | 38/3 | 21/0 | 17/3 | 0.107 |
ECOG PS (0–1/2) | 37/4 | 17/4 | 20/0 | 0.107 |
CRP, mg/dL | 2.53 (0.05, 22.68) | 3.42 (0.05, 22.68) | 1.60 (0.05, 8.25) | 0.167 |
Hb, g/dL | 12.7 (7.9, 18.8) | 12.3 (7.9, 18.8) | 13.2 (9.9, 17.1) | 0.105 |
Alb, g/dL | 3.5 (1.9, 4.3) | 3.3 (1.9, 4.3) | 3.7 (2.8, 4.3) | 0.013 |
NLR | 6.02 (1.28, 24.24) | 8.09 (1.55, 24.24) | 3.85 (1.28, 7.07) | 0.052 |
Histology (ADC/no ADC) | 28/13 | 13/8 | 15/5 | 0.506 |
Stage (III/IV) | 2/39 | 2/19 | 0/20 | 0.488 |
PD-L1expression (<50%/≥50%) * | 22/15 | 10/10 | 12/5 | 0.315 |
irAEs (G3,4 irAEs/no G3/4 irAEs) | 10/31 | 5/16 | 5/15 | >0.99 |
Objective response (CR, PR/SD, PD) # | 11/26 | 6/12 | 5/14 | 0.728 |
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Xu, S.; Miura, K.; Shukuya, T.; Harada, S.; Fujioka, M.; Winardi, W.; Shimamura, S.; Kurokawa, K.; Sumiyoshi, I.; Miyawaki, T.; et al. Early Detection of Therapeutic Benefit from PD-1/PD-L1 Blockade in Advanced Lung Cancer by Monitoring Cachexia-Related Circulating Cytokines. Cancers 2023, 15, 1170. https://doi.org/10.3390/cancers15041170
Xu S, Miura K, Shukuya T, Harada S, Fujioka M, Winardi W, Shimamura S, Kurokawa K, Sumiyoshi I, Miyawaki T, et al. Early Detection of Therapeutic Benefit from PD-1/PD-L1 Blockade in Advanced Lung Cancer by Monitoring Cachexia-Related Circulating Cytokines. Cancers. 2023; 15(4):1170. https://doi.org/10.3390/cancers15041170
Chicago/Turabian StyleXu, Shiting, Keita Miura, Takehito Shukuya, Sonoko Harada, Masahiro Fujioka, Wira Winardi, Shoko Shimamura, Kana Kurokawa, Issei Sumiyoshi, Taichi Miyawaki, and et al. 2023. "Early Detection of Therapeutic Benefit from PD-1/PD-L1 Blockade in Advanced Lung Cancer by Monitoring Cachexia-Related Circulating Cytokines" Cancers 15, no. 4: 1170. https://doi.org/10.3390/cancers15041170