First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Image Acquisition Protocol and Analysis
2.3. Laboratory Analyses
2.4. Response Assessment
2.5. Statistics
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient Characteristics | |
---|---|
Median age (range; years) | 64 (38–81) |
Male sex (n, %) | 56 (66) |
ECOG (n, %) | |
0 | 42 (49) |
1 | 27 (32) |
2+ | 16 (19) |
Presence of brain metastases (n, %) | 32 (37.6) |
Smoking history ≥ 5 pack years (n, %) | 79 (89.4) |
Pack years (mean, SD) | 44.5 (24.3) |
Therapy Characteristics | |
ICI monotherapy (n, %) | 15 (17.6) |
Median number of mono-ICI cycles (IQR) | 3 (2.5) |
Chemotherapy-ICI combination (n, %) | 70 (82.4) |
Median number of chemotherapy-ICI cycles (IQR) | 4 (2) |
Median number of mono-ICI maintenance cycles (IQR) | 2.5 (8) |
Tumor Characteristics | |
Histological subtype (n, %) | |
Adenocarcinoma | 62 (73) |
Squamous-cell carcinoma | 22 (27) |
NSCLC not otherwise specified | 1 (1) |
Positive PD-L1 status (n, %) | 49 (58) |
PD-L1 expression (n, %) | |
Not available | 5 (6) |
<1% | 31 (36) |
1–49% | 20 (24) |
≥50% | 29 (34) |
Blood Biomarkers (mean, SD) | |
C-reactive protein (mg/dL) | 3.2 (5.3) |
Lactate dehydrogenase (U/L) | 331.2 (612) |
Lymphocyte count (G/L) | 1.3 (0.78) |
PET/CT Biomarkers (mean, SD) | |
SUVmax | 16 (6.7) |
SUVmean | 7 (1.8) |
Total metabolic tumor volume (mL) | 121.6 (145.9) |
Total lesion glycolysis | 888.6 (1184.3) |
Bone marrow to liver ratio | 1.04 (0.27) |
Spleen to liver ratio | 0.81 (0.12) |
Progression-Free Survival | Overall Survival | |||||
---|---|---|---|---|---|---|
Median | 95% CI | p | Median | 95% CI | p | |
MTV ≤ 70 mL | 10 | 4–16 | 0.001 | Not reached | 7-/ | 0.004 |
MTV > 70 mL | 4 | 3–5 | 10 | 5–15 | ||
BLR ≤ 1.06 | 8 | 4–13 | 0.034 | 19 | 12-/ | 0.005 |
BLR > 1.06 | 4 | 3–6 | 6 | 4–12 |
RECIST Best Response | Disease Control Rate | |||||||
---|---|---|---|---|---|---|---|---|
Cut-Off | n | CR, PR | SD | PD | p | CR, PR, SD | p | |
MTV | ≤70 mL | 42 | 22 (52) | 12 (29) | 8 (19) | 0.026 | 34 (81) | 0.007 |
>70 mL | 43 | 14 (33) | 9 (21) | 20 (46) | 23 (53) | |||
BLR | ≤1.06 | 49 | 23 (47) | 12 (24) | 14 (29) | 0.536 | 35 (71) | 0.317 |
>1.06 | 36 | 13 (36) | 9 (25) | 14 (39) | 22 (61) |
Univariate | Multivariate | Univariate | Multivariate | |||||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | HR (95% CI) | p | |
Progression-Free Survival | Overall Survival | |||||||
ICI-monotherapy vs. chemotherapy-ICI combination | 1.33 (0.70–0.52) | 0.378 | 1.50 (0.74–3.04) | 0.258 | 4.01 (1.63–9.87) | 0.003 | ||
Sex (male vs. female) | 1.13 (0.66–1.95) | 0.654 | 1.01 (0.55–1.84) | 0.985 | ||||
Age (>70 vs. ≤70 years) | 1.18 (0.67–2.07) | 0.567 | 1.16 (0.60–2.23) | 0.666 | ||||
ECOG (2+ vs. 0,1) | 1.64 (0.88–3.03) | 0.117 | 2.20 (1.11–4.38) | 0.025 | ||||
Histology (squamous cell vs. adenocarcinoma) | 1.25 (0.69–2.24) | 0.464 | 1.53 (0.80–2.93) | 0.199 | ||||
>5 packyears (yes vs. no) | 0.55 (0.24–1.30) | 0.174 | 0.62 (0.25–1.57) | 0.315 | ||||
LDH (>250 vs. ≤250 U/L) | 1.80 (1.05–3.07) | 0.032 | 2.22 (1.23–4.00) | 0.008 | 4.34 (2.02–9.33) | <0.001 | ||
CRP (>0.5 vs. ≤0.5 mg/dL) | 1.27 (0.64–2.51) | 0.492 | 1.52 (0.68–3.40) | 0.306 | ||||
PD-L1 (pos. vs. neg) | 1.22 (0.73–2.05) | 0.457 | 1.29 (0.72–2.31) | 0.384 | 3.55 (1.54–8.14) | 0.026 | ||
Lymphocyte count (>1 vs. ≤1 G/L) | 1.16 (0.68–1.98) | 0.578 | 1.03 (0.57–1.87) | 0.914 | ||||
Presence of brain metastases (yes vs. no) | 1.70 (1.02–2.84) | 0.043 | 1.45 (0.85–2.59) | 0.170 | ||||
MTV (>70 vs. ≤70 mL) | 1.90 (1.12–3.23) | 0.017 | 1.90 (1.12–3.23) | 0.015 | 1.88 (1.03–3.42) | 0.040 | ||
BLR (>1.06 vs. ≤1.06) | 1.63 (0.98–2.72) | 0.061 | 2.10 (1.18–3.74) | 0.012 | 2.09 (1.16–3.75) | 0.014 |
Progression-Free Survival | Overall Survival | ||||||
---|---|---|---|---|---|---|---|
n | Median | 95% CI | p | Median | 95% CI | p | |
MTV ≤ 70 mL + BLR ≤ 1.06 | 31 | 9 | 4–18 | <0.001 | Not reached | 7-/ | <0.001 |
MTV ≤ 70 mL + BLR > 1.06 | 11 | 11 | 2-/- | Not reached | 3-/ | ||
MTV > 70 mL + BLR ≤ 1.06 | 18 | 5.5 | 3–13 | 17 | 6-/ | ||
MTV > 70 mL + BLR > 1.06 | 25 | 3 | 2–5 | 5 | 2–10 |
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Lang, D.; Ritzberger, L.; Rambousek, V.; Horner, A.; Wass, R.; Akbari, K.; Kaiser, B.; Kronbichler, J.; Lamprecht, B.; Gabriel, M. First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes. Cancers 2021, 13, 6096. https://doi.org/10.3390/cancers13236096
Lang D, Ritzberger L, Rambousek V, Horner A, Wass R, Akbari K, Kaiser B, Kronbichler J, Lamprecht B, Gabriel M. First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes. Cancers. 2021; 13(23):6096. https://doi.org/10.3390/cancers13236096
Chicago/Turabian StyleLang, David, Linda Ritzberger, Vanessa Rambousek, Andreas Horner, Romana Wass, Kaveh Akbari, Bernhard Kaiser, Jürgen Kronbichler, Bernd Lamprecht, and Michael Gabriel. 2021. "First-Line Pembrolizumab Mono- or Combination Therapy of Non-Small Cell Lung Cancer: Baseline Metabolic Biomarkers Predict Outcomes" Cancers 13, no. 23: 6096. https://doi.org/10.3390/cancers13236096