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Nicholas Joseph Thomas
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.14 - Time to First Progression in Patients with NSCLC with Brain Metastases Receiving 3rd Generation TKI alone vs TKI + Brain Radiation (ID 1150)
00:00 - 00:00 | Presenting Author(s): Nicholas Joseph Thomas
- Abstract
Introduction
Brain metastases are common in patients with NSCLC and represent an evolving treatment area. This is particularly relevant in patients with targetable oncogenic drivers for whom CNS penetrant therapies exist. The development of next generation TKIs such as osimertinib, alectinib and others, has allowed for treatment of Brain metastases with TKI alone or in combination with radiation. A significant challenge in clinical practice is how to utilize these two modalities to optimize patient outcomes and safety. To begin answering this question we performed a multi-institutional retrospective analysis to evaluate outcomes associated with CNS-penetrant TKI therapy alone vs CNS-penetrant TKI plus radiation (RT) in patients with EGFR or ALK-positive NSCLC metastatic to the brain. We hypothesize that CNS-penetrant TKIs alone may result in comparable outcomes to TKI + CNS radiation.
Methods
We identified 118 patients from three institutions who had new or progressive CNS metastasis at the time of initiating a CNS-penetrant TKI for EGFR or ALK positive NSCLC. Patients were categorized into groups according to treatments. 1) those who received CNS-penetrant TKI alone or 2) those who received CNS-penetrant TKI + CNS RT (SRS or WBRT) within 8 week of TKI initiation. We analyzed patients with EGFR vs ALK alterations separately. We report the time to first progression (intracranial or extracranial), intracranial progression, and treatment discontinuation. Kaplan-Meier methods and log rank tests were used to estimate time to radiographic progression with a p-value threshold <0.05.
Results
Table 1: Clinical Features and Treatment Histories
Characteristics
EGFR positive, CNS penetrant TKI n=50
EGFR positive, CNS penetrant TKI+RT n=28
ALK positive, CNS penetrant TKI n=26
ALK positive, CNS penetrant TKI+RT n=14
Duration of Follow-up
Median (Range)
18(3.0,48)
months
17(0.4, 45)
months
25(2.0, 48)
months
21(5.0, 41)
months
CNS-penetrant TKI
No.
%
No.
%
No.
%
No.
%
Osimertinib
46
92.0%
28
100.0%
0
0.0%
0
0.0%
Alectinib
0
0.0%
0
0.0%
23
88.5%
13
92.9%
Lorlatinib
0
0.0%
0
0.0%
1
3.8%
0
0.0%
Brigatinib*
0
0.0%
0
0.0%
1
3.8%
0
0.0%
Rociletinib*
4
8.0%
0
0.0%
0
0.0%
0
0.0%
Ensartinib*
0
0.0%
0
0.0%
1
3.8%
1
7.1%
Reason for TKI Discontinuation
(n=34)
(n=21)
(n=18)
(n=7)
Any Progressive disease
29
85.3%
17
81.0%
17
94.4%
6
85.7%
Death
2
5.9%
0
0.0%
0
0.0%
0
0.0%
Toxicity
1
2.9%
4
19.0%
1
5.6%
0
0.0%
Other
2
5.9%
0
0.0%
0
0.0%
1
14.3%
Treatment Prior to CNS-penetrant TKI
Any systemic
31
62.0%
10
35.7%
21
80.8%
4
28.6%
1st generation TKI
29
58.0%
8
28.6%
20
76.9%
3
21.4%
Any CNS Radiation
18
36.0%
10
35.7%
10
38.5%
3
21.4%
SRS
13
26.0%
8
28.6%
5
19.2%
1
7.1%
WBRT
3
6.0%
3
10.7%
1
3.8%
1
7.1%
SRS and WBRT
2
4.0%
2
7.1%
4
15.4%
1
7.1%
Therapy Group
CNS-penetrant TKI and SRS
0
0.0%
22
78.6%
0
0.0%
12
85.7%
CNS-penetrant TKI and WBRT
0
0.0%
6
21.4%
0
0.0%
2
14.3%
Conclusion
Demographics were balanced between groups. In log rank analysis there was no difference in outcomes between patients receiving EGFR CNS-penetrant TKI vs TKI + RT including median time to intracranial progression (TKI 14.8 months vs TKI+RT 16.4 months; p=0.79), first progression (8.4 mo vs 6.9 mo; p=0.23), or time to treatment discontinuation (17.0 mo vs 9.9 mo; p=0.57). Similarly, in the ALK subset, there was no significant difference between time to intracranial (12.0 mo vs 21.8 mo; p=0.24), first progression (8.1 mo vs 16.7 mo; p=0.3), or time to treatment discontinuation (17.0 mo vs 28.2 mo, p=0.49).*denotes clinical trial
These results indicate that in select patients with EGFR and ALK positive NSCLC with CNS disease, it may be reasonable to initiate CNS-penetrant TKI therapy with CNS surveillance instead of CNS radiation at treatment start, though this analysis may be underpowered with limited numbers and heterogeneity of patients and treatments. Further analysis with a larger cohort may strengthen this conclusion.
