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David C. Qian
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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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P76.05 - Radiotherapy with Concurrent Versus Sequential Osimertinib for Advanced Non-Small Cell Lung Cancer: a Multi-Center Toxicity Analysis (ID 874)
00:00 - 00:00 | Presenting Author(s): David C. Qian
- Abstract
Introduction
The third-generation, irreversible tyrosine kinase inhibitor osimertinib is first-line treatment for advanced non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR). Pre-clinical studies have shown synergistic anti-tumor activity of osmertinib and radiotherapy. However, the safety of radiotherapy with concurrent osimertinib has not been reported.
Methods
Medical records of all patients with EGFR-mutated NSCLC who received radiotherapy and osimertinib at an academic hospital system were reviewed. Thirty-five patients received 46 courses of radiotherapy while taking osimertinib, and 27 patients received 33 courses of radiotherapy followed by osimertinib; all patients in the latter group began taking osimertinib within 30 days of completing radiotherapy. Patients treated by radiotherapy and osimertinib at unrelated time points of disease progression were excluded. Toxicity grades experienced during radiation treatment (per Common Terminology Criteria for Adverse Events v5.0) were compared between patients who received concurrent versus sequential osimertinib.
Results
This series consists of 40 females and 22 males with advanced lung adenocarcinomas. Radiation treatment was palliative or locally consolidative (96%) in all but 2 patients. There was a trend toward more patients with oligoprogressive disease (P=0.092) and fewer patients with poor performance status (P=0.057) treated by concurrent osimertinib. Grade ≥ 3 toxicities during radiotherapy did not significantly differ between those who received osimertinib concurrently versus sequentially (7% versus 3%, P=0.859). Patients who received concurrent osimertinib had inferior progression-free survival (PFS) (HR 2.62, 95% CI 1.09–6.29, P=0.031) and similar overall survival (HR 1.39, 95% CI 0.40–4.81, P=0.60).
Patient Characteristics
Concurrent (%)
N=35
Sequential (%)
N=27
P
Median age, years
60 (range 40–76)
60 (range 38–80)
0.740
Sex
0.563
· Female
21 (60)
19 (70)
· Male
14 (40)
8 (30)
Smoking status
0.469
· Never
23 (66)
14 (52)
· Former
11 (31)
11 (41)
· Current
1 (3)
2 (7)
ECOG
0.057
· 0
11 (31)
10 (37)
· 1
16 (46)
10 (37)
· 2
8 (23)
2 (7)
· 3
0 (0)
4 (15)
· 4
0 (0)
1 (4)
Oligoprogressive disease
19 (54)
8 (30)
0.092
T classification
0.503
· T1
6 (17)
9 (33)
· T2
16 (46)
11 (41)
· T3
7 (20)
4 (15)
· T4
6 (17)
3 (11)
N classification
0.604
· N0
11 (31)
10 (37)
· N1
4 (11)
1 (4)
· N2
17 (49)
12 (44)
· N3
3 (9)
4 (15)
M classification
0.107
· M0
1 (3)
1 (4)
· M1a
7 (20)
0 (0)
· M1b
4 (11)
4 (15)
· M1c
23 (66)
22 (81)
Primary lung tumor lobe
0.286
· LUL
8 (23)
5 (19)
· LLL
7 (20)
1 (4)
· RUL
11 (31)
14 (52)
· RML
2 (6)
1 (4)
· RLL
7 (20)
6 (22)
EGFR mutation
0.400
· Exon 19 deletion
16 (46)
10 (37)
· L858R
12 (34)
9 (33)
· T790M
12 (34)
6 (22)
· Other
3 (9)
6 (22)
Osimertinib dose per day
0.715
· 80 mg
33 (94)
26 (96)
· 40 mg
2 (6)
1 (4)
Irradiated metastatic sites
0.116
· Lung/mediastinum
8 (23)
0 (0)
· Brain
14 (40)
16 (59)
· C spine
2 (6)
0 (0)
· T spine
2 (6)
2 (7)
· L spine
2 (6)
4 (15)
· Non-spinous bone
13 (37)
9 (33)
· Adrenal gland
1 (3)
0 (0)
· Liver
2 (6)
3 (11)
· Distant lymph node
0 (0)
1 (4)
Median follow-up, months
6 (range 0–27)
5 (range 1–42)
0.426
Conclusion
Treatment with radiotherapy and concurrent osimertinib confers acceptable acute toxicity. This finding is clinically significant, as delaying or holding osimertinib during radiotherapy may adversely impact disease control. The observed PFS benefit of sequential osimertinib is likely driven by selection bias for osimertinib-naїve patients whose disease has not yet been under evolutionary pressure to acquire resistance, compared to those already on osimertinib.
