
Real-world implementation of sequential targeted therapies for EGFR-mutated lung cancer
Author(s) -
Nikolaus Magios,
Farastuk Bozorgmehr,
AnnaLena Volckmar,
Daniel Kazdal,
Martina Kirchner,
Felix J.F. Herth,
Claus-Peter Heußel,
Florian Eichhorn,
Michael Meister,
Thomas Muley,
Rami A. El-Shafie,
Jürgen R. Fischer,
Martin Faehling,
Mark Kriegsmann,
Peter Schirmacher,
Helge Bischoff,
Albrecht Stenzinger,
Michael Thomas,
Petros Christopoulos
Publication year - 2021
Publication title -
therapeutic advances in medical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 49
eISSN - 1758-8359
pISSN - 1758-8340
DOI - 10.1177/1758835921996509
Subject(s) - osimertinib , medicine , afatinib , gefitinib , erlotinib , lung cancer , t790m , oncology , cancer , epidermal growth factor receptor
Background: Epidermal growth factor receptor-mutated (EGFR + ) non-small-cell lung cancer (NSCLC) patients failing tyrosine kinase inhibitors (TKI) can benefit from next-line targeted therapies, but implementation is challenging.Methods: EGFR + NSCLC patients treated with first/second-generation (1G/2G) TKI at our institution with a last follow-up after osimertinib approval (February 2016), were analyzed retrospectively, and the results compared with published data under osimertinib.Results: A total of 207 patients received erlotinib (37%), gefitinib (16%) or afatinib (47%). The median age was 66 years, with a predominance of female (70%), never/light-smokers (69%). T790M testing was performed in 174/202 progressive cases (86%), positive in 93/174 (53%), and followed by osimertinib in 87/93 (94%). Among the 135 deceased patients, 94 (70%) received subsequent systemic treatment (43% chemotherapy, 39% osimertinib), while 30% died without, either before (4%) or after progression, due to rapid clinical deterioration (22%), patient refusal of further therapy (2%), or severe competing illness (2%). Lack of subsequent treatment was significantly (4.5x, p < 0.001) associated with lack of T790M testing, whose most frequent cause (in approximately 50% of cases) was also rapid clinical decline. Among the 127 consecutive patients with failure of 1G/2G TKI started after November 2015, 47 (37%) received osimertinib, with a median overall survival of 36 months versus 24 and 21 months for patients with alternative and no subsequent therapies ( p = 0.003).Conclusion: Osimertinib after 1G/2G TKI failure prolongs survival, but approximately 15% and 30% of patients forego molecular retesting and subsequent treatment, respectively, mainly due to rapid clinical deterioration. This is an important remediable obstacle to sequential TKI treatment for EGFR + NSCLC. It pertains also to other actionable resistance mechanisms emerging under 1G/2G inhibitors or osimertinib, whose rate for lack of next-line therapy is similar (approximately 35% in the FLAURA/AURA3 trials), and highlights the need for closer monitoring alongside broader profiling of TKI-treated EGFR + NSCLC in the future.