Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Patient Characteristics
2.2. Response Assessment
2.3. Survival Outcomes
3. Discussion
4. Methods
4.1. Patient Population/Study Design
4.2. Outcome Assessment
4.3. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Patient Characteristics | Total Patients with Brain Metastases (n = 51) | Total Patient Population (n = 280) | |
---|---|---|---|
Age (years) | Median | 69 | 69.8 |
Range | 40–84 | 35–84 | |
Gender (male) | 54.9% | 55.7% | |
Performance status 0–1 | 74.5% | 83.5% | |
Smoking status (former or active) | 86.3% | 92.8% | |
Histology (non-squamous) | 84.3% | 67% | |
PD-L1 expression extracranially | <1% | 7.8% | 10% |
1%≤PD-L1<50% | 25.5% | 28.9% | |
PD-L1≥50% | 58.5% | 34.6% | |
No data | 19.6% | 26% | |
Line of treatment of ICI administration (first line) | 19.6% | 21% | |
Types of ICI Therapy Administered | Atezolizumab | 3.9% | |
Nivolumab | 51.0% | ||
Pembrolizumab | 45.1% | ||
Mean number of ICI cycles | 6.2 (range: 1–42) | ||
Primary CNS metastases at diagnosis | 60.8% | ||
Neurological symptoms associated with CNS metastases | 43.1% | ||
Radiological evaluation method of CNS metastases (MRI) | 60.8% | ||
Size of largest CNS metastasis (mm) | Median | 17 | |
Range | 4–50 | ||
> 3 CNS metastases | 33.3% | ||
High disease burden * | 31.4% | ||
Steroid administration > 10 mg for ≥10 days | 54.1% | ||
Active brain metastases | 84.2% | ||
Previous local CNS treatment modality | WBRT | 33.3% | |
Surgical excision | 5.9% | ||
SRS | 29.4% | ||
Surgical excision + SRS | 2.0% | ||
WBRT + SRS | 2.0% | ||
No local treatment | 27.5% | ||
Timeline of local CNS treatment modality administration | ≥3 months before ICI administration | 33.3% | |
<3 months before or after ICI administration | 39.2% | ||
No local treatment | 27.4% | ||
Range | 0.4–22.9 |
Patient Outcomes | Total (n = 33) | Total (n = 51) | 95% Confidence Intervals | |
---|---|---|---|---|
Intracranial response rates to ICIs | CRi | 3.0% | ||
PRi | 21.2% | |||
SDi | 24.2% | |||
PDi | 51.5% | |||
Intracranial response rates to ICIs in patients with active brain metastases | CRi | 4.0% | ||
PRi | 20.0% | |||
SDi | 8.0% | |||
PDi | 68.0% | |||
Duration of intracranial response (months) (patients that achieved PRi or SDi) | Median | 7.5 | 0.0–18.5 | |
Range | 0.5–22.9 | |||
Disease progression | 88.2% | |||
Death | 78.4% | |||
Time to intracranial progression (months) | Median | 2.5 | 1.5–3.6 | |
Range | 0.2–22.9 | |||
PFS (months) | Median | 1.9 | 1.5–2.3 | |
Range | 0.1–22.1 | |||
OS (months) | Median | 5.7 | 2.6–8.9 | |
Range | 0.4–30.3 | |||
Follow-up (months, median) | 5.7 | 2.2–9.3 |
COX REGRESSION | PFS | OS | ||
---|---|---|---|---|
Univariate Analysis | HR (95% CI) | p-Value | HR (95% CI) | p-Value |
Age > 70 years old | 0.858 (0.648–1.136) | 0.285 | 0.794 (0.574–1.099) | 0.164 |
Performance status = 2 | 1.517 (1.064–2.163) | 0.021 | 2.132 (1.445–3.144) | <0.001 |
Non-squamous histology | 0.999 (0.747–1.337) | 0.997 | 1.065 (0.765–1.484) | 0.708 |
ICI administration as 2nd or subsequent line of therapy | 2.284 (1.519–3.436) | < 0.001 | 2.840 (1.665–4.846) | <0.001 |
Brain metastases | 1.838 (1.314–2.569) | < 0.001 | 1.810 (1.230–2.662) | 0.003 |
High disease burden * | 1.746 (1.256–2.427) | 0.001 | 1.961 (1.363–2.821) | <0.001 |
PD-L1 < 50% | 2.083 (1.464–2.958) | < 0.001 | 1.915 (1.269–2.898) | 0.002 |
Multivariate Analysis | ||||
Performance status = 2 | 1.377 (0.882–2.149) | 0.159 | 2.106 (1.269–3.497) | 0.004 |
ICI administration as 2nd or subsequent line of therapy | 1.672 (1.022–2.736) | 0.041 | 2.898 (1.638–5.125) | <0.001 |
Brain metastases | 2.265 (1.529–3.356) | < 0.001 | 1.577 (0.965–2.597) | 0.069 |
High disease burden * | 1.447 (0.909–2.303) | 0.119 | 2.219 (1.380–3.579) | 0.001 |
PD-L1 < 50% | 1.709 (1.184–2.645) | 0.005 | 1.390 (0.861–2.242) | 0.178 |
Variable | OVERALL SURVIVAL | |||
---|---|---|---|---|
Univariate | Multivariate | |||
HR (CI 95%) | p-Value | HR (CI 95%) | p-Value | |
Age > 70 years old | 1.723 (0.913–3.252) | 0.093 | ||
Performance status = 2 | 1.460 (0.739–2.883) | 0.276 | ||
Non-adenocarcinoma histology | 2.150 (0.937–4.931) | 0.071 | ||
Second or subsequent line of ICI administration | 1.628 (0.680–3.898) | 0.274 | ||
High disease burden *1 | 2.390 (1.161–4.922) | 0.018 | 2.390 (1.161–4.922) | 0.018 |
Non-primary CNS metastases *2 | 1.436 (0.760–2.711) | 0.265 | ||
PD-L1 extracranially ≥ 50% | 1.021 (0.506–2.058) | 0.954 |
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Skribek, M.; Rounis, K.; Makrakis, D.; Agelaki, S.; Mavroudis, D.; De Petris, L.; Ekman, S.; Tsakonas, G. Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting. Cancers 2020, 12, 3707. https://doi.org/10.3390/cancers12123707
Skribek M, Rounis K, Makrakis D, Agelaki S, Mavroudis D, De Petris L, Ekman S, Tsakonas G. Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting. Cancers. 2020; 12(12):3707. https://doi.org/10.3390/cancers12123707
Chicago/Turabian StyleSkribek, Marcus, Konstantinos Rounis, Dimitrios Makrakis, Sofia Agelaki, Dimitris Mavroudis, Luigi De Petris, Simon Ekman, and Georgios Tsakonas. 2020. "Outcome of Patients with NSCLC and Brain Metastases Treated with Immune Checkpoint Inhibitors in a ‘Real-Life’ Setting" Cancers 12, no. 12: 3707. https://doi.org/10.3390/cancers12123707