Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Statistical Analyses
3. Results
3.1. Survival Analysis of the Whole Cohort
3.2. Toxicity
3.3. Prediction of Response
3.4. Prognostic Value of Different Markers and Scores
3.5. Multivariate Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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n = 44 | |
---|---|
Male (n (%)) | 25 (56.8%) |
Female (n (%)) | 19 (43.2%) |
Age (mean ± Sdev) | 64.3 ± 9.9 |
Males | 65.52 ± 10.4 |
Females | 62.6 ± 9.2 |
ECOG-PS | |
0 | 6 (13.6%) |
1 | 19 (43.2%) |
2 | 14 (31.8%) |
3 | 5 (11.4%) |
Smoking status (n (%)) | |
Current smoker | 9 (20.5%) |
Former smoker | 35 (79.5%) |
Pharmaceutical form (n (%)) | |
Intravenous | 40 (90.9%) |
Oral | 4 (9.1%) |
Median of applied cycles [range] | 3 (1–17) |
Mean applied dosage [range] | 1.22 mg/m2 [0.625–2.4 mg/m2] |
Median time from first diagnosis until topotecan | 8.3 months |
Median time from last treatment until topotecant (treatment free intervall, TFI) | 1.7 months |
<3 months (n (%)) | 32 (72.7) |
≥3 months | 12 (27.3) |
Prior IO treatment (n (%)) | |
Yes | 15 (34.1%) |
No | 29 (65.9%) |
Active brain metastases (n (%)) | |
Yes | 15 (34.1%) |
No | 29 (64.9%) |
WBRT before topotecan (n (%)) | |
Yes | 20 (45.5%) |
No | 24 (54.5%) |
1st-line treatment (n (%)) | |
Chemo(-immuno) therapy | 31 (70.5%) |
Radiochemotherapy | 13 (29.5%) |
Best response to topotecan treatment (n (%)) | |
PR | 6 (13.6%) |
SD | 8 (18.2%) |
PD | 23 (52.3%) |
Death | 7 (15.9%) |
Median PFS [CI 95%] | HR [CI 95%] | p-Value [Log Rank] | Median OS [CI 95%] | HR [CI 95%] | p-Value [Log Rank] | |
---|---|---|---|---|---|---|
Gender | ||||||
Male | 1.6 [1.1–2.1] | p = 0.014 | 4.0 [2.7–5.3] | p = 0.043 | ||
Female | 3.3 [1.5–5.0] | 0.45 [0.2–0.9] | 8.5 [6.4–10.6] | 0.48 [0.2–0.9] | ||
ECOG | ||||||
<2 | 3.3 [1.2–5.3] | 0.40 [0.2–0.8] | p = 0.004 | 8.2 [6.1–10.2] | 0.48 [0.2–0.9] | p = 0.036 |
≥2 | 1.5 [1.2–1.9] | 4.0 [3.2–4.8] | ||||
Age | ||||||
<70 years | 1.9 [0.4–3.5] | p = 0.433 | 5.9 [2.0–9.8] | p = 0.713 | ||
≥70 years | 1.9 [1.5–2.3] | 1.2 [0.6–2.6] | 4.0 [3.4–4.6] | 1.1 [0.5–2.6] | ||
Time until topotecan | ||||||
≤8.3 months | 1.9 [1.5–2.3] | p = 0.719 | 4.4 [3.6–5.1] | p = 0.484 | ||
>8.3 months | 1.9 [0.3–3.5] | 0.66 [0.3–1.3] | 8.6 [4.4–12.7] | 0.78 [0.4–1.6] | ||
Median time from last treatment until topotecant (treatment free interval, TFI) | ||||||
<3 months (n (%)) | 1.9 [1.6–2.2] | 1.9 [0.6–5.8] | p = 0.205 | 5.0 [3.4–6.5] | 1.5 [0.1–2.5] | p = 0.711 |
≥3 months | 1.9 [0.0–5.8] | 9.1 [1.7–16.6] | ||||
Mean topotecan dosage | ||||||
<1.25 mg/m2 | 3.3 [1.2–5.3] | p = 0.547 | 8.1 [3.9–12.3] | p = 0.111 | ||
≥1.25 mg/m2 | 1.6 [1.2–2.0] | 1.4 [0.8–2.7] | 4.3 [3.1–5.7] | 1,7 [0.9–3.5] | ||
Prior IO treatment | ||||||
Yes | 1.8 [1.2–2.4] | p = 0.903 | 5.0 [0.8–9.1] | p = 0.855 | ||
No | 2.1 [0.4–3.9] | 0.9 [0.5–1.6] | 5.9 [0.5–11.4] | 2.1 [0.5–8.8] | ||
Active brain metastases | ||||||
No | 3.0 [1.5–4.6] | p = 0.028 | 7.1 [2.5–11.7] | p = 0.633 | ||
Yes | 1.6 [1.3–1.9] | 1.9 [1.0–3.6] | 4.7 [3.7–5.7] | 1.2 [0.6–2.6] | ||
WBRT before topotecan | ||||||
No | 2.1 [0.0–4.4] | p = 0.475 | 7.1 [2.5–11.7] | p = 0.571 | ||
Yes | 1.8 [1.7–2.0] | 1.1 [0.6–2.0] | 5.0 [2.7–7.2] | 0.8 [0.4–1.6] | ||
1st-line treatment | ||||||
Chemo(-immuno) therapy | 1.8 [0.9–2.8] | p = 0.638 | 4.4 [3.6–5.2] | p = 0.089 | ||
Radiochemotherapy | 1.9 [1.5–2.4] | 0.7 [0.3–1.4] | 12.0 [6.8–17.2] | 0.5 [0.2–1.1] |
Categorial Variables | |||
Variable | p-Value | Variable | p-Value |
Gender (male vs. women) | p = 0.054 | Active brain metastases (yes vs. no) | p = 0.598 |
ECOG (0 vs. 1 vs. 2 vs. 3) | p = 0.085 | WBRT (yes vs. no) | p = 0.813 |
Application (p.o. vs. i.v.) | p = 0.152 | 1st-line treatment (CX vs. RCT) | p = 0.420 |
GPS (0 vs. 1 vs. 2) | p = 0.207 | Age (<70 vs. ≥70) | p = 0.709 |
Prior IO treatment (yes vs. no) | p = 0.128 | Time till Topotecan (≤8.3 vs. >8.3 months) | p = 0.195 |
Dosage (<1.25 mg/m2 vs. ≥1.25 mg/m2) | p = 0.010 | LDH (≤250 vs. >250 U/l) | p = 0.195 |
CRP (≤0.5 vs. >0.5 mg/dL | p = 0.32 | NLR (≤6 vs. >6) | p = 0.598 |
Sodium (<135 vs. ≥135 mmol/L) | p =0.092 | TLR (≤200 vs. >200) | p = 1 |
PNI (<40 vs. ≥40) | p = 0.262 | SII (<1500 vs. ≥1500) | p = 0.349 |
PI (1 + 2 vs. 3 + 4) | p = 0.287 | ||
Continuous Variables | |||
Variable | p-Value | Variable | p-Value |
Age | p = 0.830 | NLR | p = 0.257 |
Mean topotecan dosage | p = 0.009 | TLR | p = 0.860 |
LDH | p = 0.059 | PNI | p = 0.174 |
CRP | p = 0.007 | SII | p = 0.166 |
Sodium | p = 0.419 |
Median PFS [CI 95%] | HR [CI 95%] | p-Value [Log Rank] | Median OS [CI 95%] | HR [CI 95%] | p-Value [Log Rank] | |
---|---|---|---|---|---|---|
LDH | ||||||
≤250 U/L | 3.0 [0.9–5.1] | p = 0.006 | 8.5 [4.0–13.1] | p = 0.370 | ||
>250 U/L | 1.6 [1.2–2.1] | 2.2 [1.2–4.3] | 3.6 [1.8–5.4] | 1.4 [0.7–2.8] | ||
CRP | ||||||
≤0.5 mg/dL | 3.4 [0.7–6.0] | p = 0.089 | 9.1 [5.7–12.6] | p = 0.102 | ||
>0.5 mg/dL | 1.6 [1.3–2.0] | 1.6 [0.8–3.1] | 4.4 [2.7–6.0] | 1.6. [0.8–3.1] | ||
NLR | ||||||
≤6 | 3.0 [0.9–5.1] | p = 0.002 | 8.2 [4.1–12.2] | p = 0.01 | ||
>6 | 1.3 [1.1–1.6] | 2.5 [1.3–4.9] | 4.4 [1.8–7.1] | 2.6 [1.2–5.5] | ||
Sodium | ||||||
<135 mmol/L | 1.6 [1.5–1.7] | p = 0.066 | 4.4 [2.9–5.8] | p = 0.029 | ||
≥135 mmol/L | 3.0 [1.6–4.4] | 0.5 [0.3–1.1] | 8.1 [4.1–12.2] | 0.4 [0.2–0.9] | ||
TLR | ||||||
≤200 | 3.0 [0.4–5.7] | p = 0.020 | 8.1 [3.0–13.2] | p = 0.734 | ||
>200 | 1.9 [1.5–2.3] | 1.9 [1.0–3.7] | 4.7 [3.5–5.8] | 1.1 [0.6–2.2] | ||
GPS | ||||||
0 | 3.0 [0.4–5.6] | p = 0.011 | 9.1 [5.6–12.66] | p = 0.008 | ||
≥1 | 1.6 [1.2–2.1] | 2.3 [1.2–4.6] | 4.0 [2.2–5.7] | 2.6 [1.3–5.4] | ||
PNI | ||||||
<40 | 1.4 [1.2–1.7] | p = 0.015 | 2.4 [1.2–3.6] | p < 0.001 | ||
≥40 | 2.5 [0.9–4.1] | 0.4 [0.2–0.9] | 8.6 [2.4–8.8] | 0.2 [0.1–0.4] | ||
SII | ||||||
<1500 | 3.0 [0.9–5.1] | p = 0.014 | 8.1 [3.0–13.3] | p = 0.431 | ||
≥1500 | 1.6 [1.3–1.8] | 2.1 [1.1–3.9] | 4.7 [2.9–6.5] | 1.3 [0.7–2.7] | ||
PI | ||||||
1–2 | 3.3 [2.6–4.0] | p = 0.003 | 9.1 [2.4–15.9] | p = 0.001 | ||
3–4 | 1.6 [1.3–1.9] | 2.4 [1.3–4.7] | 3.6 [2.9–4.2] | 3.2 [1.5–6.6] |
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Lambrecht, L.; Arnold, P.; Behr, J.; Mertsch, P.; Tufman, A.; Kauffmann-Guerrero, D. Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment. Diagnostics 2024, 14, 1572. https://doi.org/10.3390/diagnostics14141572
Lambrecht L, Arnold P, Behr J, Mertsch P, Tufman A, Kauffmann-Guerrero D. Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment. Diagnostics. 2024; 14(14):1572. https://doi.org/10.3390/diagnostics14141572
Chicago/Turabian StyleLambrecht, Laura, Paola Arnold, Jürgen Behr, Pontus Mertsch, Amanda Tufman, and Diego Kauffmann-Guerrero. 2024. "Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment" Diagnostics 14, no. 14: 1572. https://doi.org/10.3390/diagnostics14141572
APA StyleLambrecht, L., Arnold, P., Behr, J., Mertsch, P., Tufman, A., & Kauffmann-Guerrero, D. (2024). Topotecan in a Real-World Small-Cell Lung Cancer Cohort: Prognostic Biomarkers Improve Selection of Patients for Second-Line Treatment. Diagnostics, 14(14), 1572. https://doi.org/10.3390/diagnostics14141572