Genome-guided targeted therapy combination improves survival in patients with advanced EGFR mutation positive NSCLC failing osimertinib
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AbstractBackground: Acquired genomic alternations are known mechanisms of resistance to
osimertinib in patients with advanced epidermal growth factor receptor (EGFR)
positive non-small cell lung cancer (NSCLC). Addition of genome-guided targeted
therapy (GGTT) to osimertinib may improve treatment outcomes.
Methods: This retrospective study reviewed 226 metastatic EGFR mutation positive
NSCLC patients who received systemic therapy after failing osimertinib. Primary
endpoints include time-to-treatment failure (TTF) and overall survival (OS) from postosimertinib failure.
Results: Total of 68 patients had genomic analysis for osimertinib resistance and 21
(30%) had targetable genomic alternations. Out of which, 17 received osimertinib plus
GGTT (13 MET amplification, 2 ALK rearrangement, 1 RET rearrangement and 1 BRAF
V600E mutation) and 209 patients received chemotherapy. Median follow-up were
10.0 and 30.1 months for GGTT and chemotherapy group respectively. The GGTT
group achieved significantly longer TTF (not reached [NR] vs 5.1 months, HR 0.19,
95% CI 0.08-0.48, p<0.001) and OS (NR versus 10.5 months, HR 0.27, 95% CI 0.09-
0.86, p¼0.026) compared to those receiving chemotherapy. These results remained
significant after multivariate analysis (Table). In subgroup analysis, TTF of GGTT group
was superior to chemotherapy alone (n¼148) (NR versus 4.5 months, HR 0.18,
p<0.001), chemotherapy plus osimertinib (n¼41) (NR versus 6.2 months, HR 0.23,
p¼0.003) and chemotherapy plus anti-PD(L)1 plus anti-VEGF (n¼20) (NR versus 6.3
months, HR 0.25, p¼0.009), respectively.
Conclusions: The combination of GGTT and osimertinib improves TTF and OS in EGFR
mutation positive NSCLC patients failing osimertinib. Future prospective comparative
study is warranted.
osimertinib in patients with advanced epidermal growth factor receptor (EGFR)
positive non-small cell lung cancer (NSCLC). Addition of genome-guided targeted
therapy (GGTT) to osimertinib may improve treatment outcomes.
Methods: This retrospective study reviewed 226 metastatic EGFR mutation positive
NSCLC patients who received systemic therapy after failing osimertinib. Primary
endpoints include time-to-treatment failure (TTF) and overall survival (OS) from postosimertinib failure.
Results: Total of 68 patients had genomic analysis for osimertinib resistance and 21
(30%) had targetable genomic alternations. Out of which, 17 received osimertinib plus
GGTT (13 MET amplification, 2 ALK rearrangement, 1 RET rearrangement and 1 BRAF
V600E mutation) and 209 patients received chemotherapy. Median follow-up were
10.0 and 30.1 months for GGTT and chemotherapy group respectively. The GGTT
group achieved significantly longer TTF (not reached [NR] vs 5.1 months, HR 0.19,
95% CI 0.08-0.48, p<0.001) and OS (NR versus 10.5 months, HR 0.27, 95% CI 0.09-
0.86, p¼0.026) compared to those receiving chemotherapy. These results remained
significant after multivariate analysis (Table). In subgroup analysis, TTF of GGTT group
was superior to chemotherapy alone (n¼148) (NR versus 4.5 months, HR 0.18,
p<0.001), chemotherapy plus osimertinib (n¼41) (NR versus 6.2 months, HR 0.23,
p¼0.003) and chemotherapy plus anti-PD(L)1 plus anti-VEGF (n¼20) (NR versus 6.3
months, HR 0.25, p¼0.009), respectively.
Conclusions: The combination of GGTT and osimertinib improves TTF and OS in EGFR
mutation positive NSCLC patients failing osimertinib. Future prospective comparative
study is warranted.
All Author(s) ListM. S. C. Li, K. K. S. Mok, G. Tsui, K. W. C. Lee, K. C. Lam, H. H. F. Loong, F. S. T. Mok, L. L. Chan, K. Yan, T. Y. J. Ng, D. Johnson, B. H. W. Lam, W. K. Y. Wong, A. C. C. Chen, M. M. P. Lee, O. H. Chen, T. S. K. Mok
Name of ConferenceEuropean Society for Medical Oncology Congress Asia (ESMO Asia) 2023
Start Date of Conference01/12/2023
End Date of Conference03/12/2023
Place of ConferenceSingapore
Country/Region of ConferenceSingapore
Proceedings TitleAnnals of Oncology
Year2023
Month11
Volume Number34
Issue NumberSuppl. 4
Article numberS1690
LanguagesEnglish-United Kingdom
KeywordsEGFR
