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Jun Ma
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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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P76.88 - Real-World Data of Osimertinib in Patients with Metastatic EGFRm+ NSCLC who Progressed on First-Line EGFR TKIs (ID 3646)
00:00 - 00:00 | Presenting Author(s): Jun Ma
- Abstract
Introduction
Osimertinib is a third-generation epidermal-growth-factor-receptor tyrosine kinase inhibitor (EGFR-TKI) approved for use in EGFR-mutant lung cancer. We examined its performance in the 2nd/subsequent line setting after resistance to 1st/2nd generation EGFR-TKI.
Methods
We reviewed n=202 patients who received Osimertinib from July 2015 to July 2018 in the 2nd/subsequent line after progression on prior EGFR-TKI. Clinical data including patient characteristics, primary EGFR mutation, T790M mutation status, presence of baseline brain metastases (BM), first-line EGFR-TKI use and survival outcomes were retrospectively analyzed.
Results
Complete data from 193 patients was analyzed. Median age at diagnosis was 63 years (IQR
55-70), 59.6% patients were females, 79.8% never-smokers, 79.3% ECOG 0-1 at start of osimertinib. Majority had EGFR exon 19 (60.6%) and exon 21 (32.1%) mutations at diagnosis. At resistance, T790M mutation was positive in 151 (78.2%) patients: 96/193 (49.2%) tumour samples and 63/193 (32.6%) plasma samples, negative in 20 (10.4%) and unknown in 22 (11.4)%. 100 (51.8%) patients received osimertinib as 2nd line, and the rest in 3rd/subsequent line. 144 (75%) received first-line gefitinib or erlotinib (1G-TKI), 47 (24%) afatinib and 2 (1%) others. Baseline BM was present in 55/192 (28.5%) patients, 37/55 (67.3%) had whole brain radiotherapy (WBRT). Baseline BM were significantly more common in the afatinib group compared to 1G-TKI group (46.8% vs 22.9%, p=0.002).
After median follow up of 37 (95% CI 31.8-41.6) months, median progression-free survival (PFS) was 10.3 (95% CI 8.64-11.50) months and median overall survival (OS) 20 (95% CI 15.61-23.13) months. PFS was 6.3 months for those treated with prior afatinib vs 10.5 months in those who received 1G-TKI (HR 1.57, p=0.01). OS in T790M+ patients was 22.6 months vs 7.9 months in T790M-negative patients (HR 0.43, p=0.001), and PFS was 11.2 months vs 3.1 months respectively (HR 0.52, p=0.01). PFS for second-line use of osimertinib was 10.0 (95% CI 6.34-12.29) months and 10.3 (95% CI 8.05-14.03) months for third-line/beyond (p=0.3); OS was 20.5 (95% CI 15.18-23.89) and 18.7 (95% CI 14.13-23.75) months, respectively (p=0.7). Tumour T790M-positivity was associated with longer PFS (p=0.007) and OS (p=0.01) than tumour T790M-negative patients, but significance was not seen with plasma T790M-positivity.
Physician-assessed overall response rate to osimertinib was 43% (95% CI 35.9-50.3): 48.3% in T790M+ vs 20% in T790M-negative patients. Duration of response was 11.1 (95% CI 8.28-13.67) months in T790M-positive patients.
By multivariable analysis (MVA), ECOG ≥2 (HR 2.53, p<0.001) was associated with shorter OS, and presence of T790M+ with longer OS (HR 0.50, p=0.008). Presence of T790M+ was significantly associated with longer PFS compared to T790M-negative (HR 0.57, p=0.03). ECOG ≥2 (HR 2.10, p<0.001) and first-line afatinib use (HR 1.58, p=0.009) compared to 1G-TKI, were significantly associated with shorter PFS by MVA.
Conclusion
In our cohort, we confirmed that osimertinib is effective even beyond second-line for advanced EGFRm+ NSCLC for T790M+ patients. The shorter PFS in patients who received first-line Afatinib compared to 1G-TKI may be explained by significantly higher proportion of baseline BM in this group. EGFR T790M-negative disease at resistance remain an unmet treatment need.