Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR mutant lung cancer: Distinct natural history of patients with tumors harboring the T790M mutation

By G. Oxnard, M. Arcila, C. Sima, Gregory Riely, J. Chmielecki, M. Kris, William Pao, Marc Ladanyi, Vincent A. Miller. Clinical Cancer Research, 2010

619 citations recorded by the source corpus.

Purpose: Patients with epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma develop acquired resistance to EGFR tyrosine kinase inhibitors (TKI) after a median of 10 to 16 months. In half of these cases, a second EGFR mutation, T790M, underlies acquired resistance. We undertook this study to examine the clinical course of patients harboring the T790M mutation following progression on TKI. Experimental Design: EGFR-mutant lung cancer patients with acquired resistance to EGFR TKIs were identified as part of a prospective rebiopsy protocol in which postprogression tumor specimens were collected for molecular analysis. Postprogression survival and characteristics of disease progression were compared in patients with and without T790M. Results: We identified T790M in the initial rebiopsy specimens from 58 of 93 patients (62%, 95% CI: 52–72). T790M was more common in biopsies of lung/pleura tissue and lymph nodes than in more distant sites (P = 0.014). Median postprogression survival was 16 months (interquartile range = 9–29 months); patients with T790M had a significantly longer postprogression survival (P = 0.036). Patients without T790M more often progressed in a previously uninvolved organ system (P = 0.014) and exhibited a poorer performance status at time of progression (P = 0.007). Conclusions: Among patients with acquired resistance to EGFR TKIs, the presence of T790M defines a clinical subset with a relatively favorable prognosis and more indolent progression. Knowledge of T790M status is therefore important both for the clinical care of these patients and for the optimal design and interpretation of clinical trials in this setting. Clin Cancer Res; 17(6); 1616–22. ©2010 AACR.

Subfields: Oncology, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/2107b601caecc229dd449a985080b566a2d53825

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. William Pao
2. Gregory Riely
3. Vincent A. Miller
4. M. Kris

In Pulmonary and Respiratory Medicine

1. William Pao
2. Gregory Riely
3. Vincent A. Miller
4. B. Hughes
5. B. Chan
6. M. Kris
7. Marc Ladanyi
8. Jin-Yuan Shih

Citations in the corpus

• Osimertinib in Untreated EGFR‐Mutated Advanced Non–Small‐Cell Lung Cancer (2018, neutral): “Paronychia 91 (33) 48 (17) 42 (15) 1 (<1) 0 84 (30) 52 (19) 30 (11) 2 (1) 0”
• Noninvasive detection of response and resistance in EGFR-mutant lung cancer using quantitative next-generation genotyping of cell-free plasma DNA (2014, neutral): “Firstly, acquired T790M has been associated with indolent growth and a favorable prognosis compared to T790M-negative acquired resistance (25).”
• Mechanisms of Resistance to Crizotinib in Patients with ALK Gene Rearranged Non-Small Cell Lung Cancer (2012, positive): “In contrast, EGFR T790M mutations confer impaired growth compared with cells carrying EGFR-activating mutations alone (25).”
• Targeted therapy for non-small cell lung cancer: current standards and the promise of the future. (2015, background): “Unfortunately a wide variety of mechanisms are being discovered including; ALK amplification, EGFR/HER1, HER2 and HER3 up-regulation, cKIT amplification and various ALK mutations including L1196M (analogous to T790M for EGFR) (107-110).”
• Analysis of Tumor Specimens at the Time of Acquired Resistance to EGFR TKI therapy in 155 patients with EGFR mutant Lung Cancers (2013, methodology): “cers who had an initial response to erlotinib or gefitinib (13).”