EGFR mutation testing and treatment decisions in patients progressing on first- or second-generation epidermal growth factor receptor tyrosine kinase inhibitors

Abstract

Background: The objective of this study was to investigate real-world EGFR mutation testing in patients with metastatic non-small cell lung cancer (NSCLC) upon progression on first−/second-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI), and subsequent treatments received. Methods: Flatiron Health electronic health records-derived database was used to identify adult patients with metastatic NSCLC treated with first−/second-generation EGFR-TKI from 11/2015-09/2017, with start of first EGFR-TKI defined as the index date. Patients were stratified by receipt of EGFR-TKI as first-line (1 L) or later-line (2 L+) treatment. Mutation testing and subsequent therapies following first−/second-generation EGFR-TKI were described. Results: Overall, 782 patients (1 L = 435; 2 L+ =347) were included. Median age was 69.0 years, 63.6% were female, 56.3% were white, 87.1% were treated in community-based practices, and 30.1% of patients died during the study period; median follow-up was 309.0 days. Among the 294 (1 L = 160; 2L+ =134) patients who received subsequent therapies, treatments included chemotherapy only (1 L = 15.6%; 2L+ =21.6%), immunotherapy only (1 L = 13.8%; 2 L+ =41.0%), and targeted therapies (1 L = 70.0%; 2 L+ =36.6%). Specifically, 40 (25.0%) 1 L patients and 7 (5.2%) 2 L+ patients received osimertinib as subsequent therapy. Before the start of subsequent therapy, EGFR T790M resistance mutation testing was performed in 88 (29.9%) patients (1 L = 63 [39.4%]; 2 L+ =25 [18.7%]). Of these patients, 25 (28.4%) were T790M positive, among whom 24 (96.0%) received osimertinib. Conclusions: A third of patients received subsequent therapies on disease progression; only 30% of these were tested for EGFR-TKI resistance mutation, prior to receiving subsequent therapies. These results highlight the importance of choosing treatments in the 1 L setting that optimize benefits for patients with EGFRmutated NSCLC.

Real-world Treatment Patterns in Patients with EGFR Mutation-positive NSCLC Receiving a First-Line, First- or Second-generation EGFR Tyrosine Kinase Inhibitor in South Korea and Taiwan

“…The number of patients in the Taiwan cohort with T790M-positive tumors was low (18% vs 43% in the South Korean cohort), which is more similar to that observed in other real-world studies with Asian and non-Asian cohorts (approximately 30%) [16][17][18] than in clinical trials (approximately 50%) [15,37]. It is worth noting that the incidence of uncommon/complex EGFR mutations (20%) in the Taiwan cohort was slightly higher than rates seen in other studies (12-16%) of Asian patient cohorts [38][39].…”

“…Despite initial efficacy, most patients with EGFRm advanced or metastatic NSCLC treated with a 1L 1G/2G EGFR-TKI develop resistance, with disease progression occurring after a median of 8 to 16 months [12][13][14]. The EGFR T790M acquired resistance mutation has been observed in approximately 50% of patients from a meta-analysis of clinical trials [15] while rates of approximately 30% have been reported in real-world studies [16][17][18].…”

Real-World Utilization of Target- and Immunotherapies for Lung Cancer: A Scoping Review of Studies Based on Routinely Collected Electronic Healthcare Data

“…Screening of titles and abstracts allowed the selection of 131 potentially eligible studies. Among them, a total of 32 studies fulfilled the eligibility criteria and were finally included into the review [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. No further studies were retrieved through a snowballing search.…”

“…Twenty-six out of 32 included studies used rcEHD from North America [ 27 , 28 , 29 , 30 , 31 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ], two studies used data from Asia [ 24 , 32 ], three from Europe [ 26 , 42 , 55 ], and one from Australia [ 25 ]. Thirteen studies used record linkage of ≥1 type of data source [ 24 , 25 , 26 , 28 , 30 , 32 , 35 , 36 , 42 , 44 , 45 , 50 , 55 ], while 19 studies were based on one data source type only.…”

A Targeted Gene Panel for Circulating Tumor DNA Sequencing in Neuroblastoma

“…A variety of technical approaches have been optimized to detect diagnostic/prognostic/ therapeutic markers in ctDNA with great sensitivity, including BEAMing technologies (5), panel sequencing of cancerassociated genes (6,7), targeted amplicon sequencing (8,9) and droplet digital PCR technologies (10). Currently, the FDAapproved qPCR test to identify Epidermal Growth Factor Receptor (EGFR) mutations, is a diagnostic test that replaces the tissue biopsy in patients with metastatic non-small cell lung cancer who would be eligible for treatment with EGFR-targeted therapy (erlotinib) (11). Nevertheless, comprehensive genomic analysis such as Whole Exome Sequencing (WES) or Whole Genome Sequencing (WGS) of ctDNA, cannot be considered in diagnostic routines because of the detection of large numbers of variants with uncertain significance.…”