Genomic testing and treatment landscape in patients with advanced non-small cell lung cancer (aNSCLC) using real-world data from community oncology practices.

Abstract

1585 Background: While aNSCLC is a leading cause of US cancer deaths, targeted therapies and immune checkpoint inhibitors (ICPi) have emerged as important new treatment options for these pts NCCN guidelines recommend testing of eight genes in aNSCLC patients at diagnosis. Targetable alterations (TA) in four genes, EGFR, ALK, ROS1, and BRAF, are associated with FDA-approved therapies. The labels for ICPis indicate that pts with TAs in EGFR and ALK are not candidates for first line treatment with ICPi. Methods: The Integra Connect database, which includes electronic medical record (EMR) and claims data on approximately 600,000 cancer patients, was queried across five community oncology practices (289 oncologists) to identify aNSCLC patients (stage 3B or 4) treated since January 2017. Manual review of charts was done to abstract tumor type/stage, drug regimens, and evidence of somatic genetic testing. A Wilcoxon rank sum test was used to test difference in time to results (TTR) for blood- vs tissue-based tests. Results: A total of 1,203 aNSCLC patients were identified. Testing rates varied from 54% for EGFR to 22% for all 4 genes (table). 163 patients had a TA in EGFR, ALK, ROS1 or BRAF, and 55% of these pts did not receive targeted therapy. 84 pts with TA’s in EGFR or ALK had no evidence of progression on targeted therapy, yet 31 (37%) received an ICPi; 24% had the TA test result prior to ICPi use and 13% received the TA result after starting ICPi. Median TTR for blood-based somatic tests was shorter than tissue-based tests (4 vs 14 days, p-value= 3.5-e07). Conclusions: Our analysis in the community oncology setting for aNSCLC pts finds evidence of underutilization of genomic testing, underutilization of targeted therapies, and ICPi use outside of label. Further research is needed to identify strategies to increase testing in aNSCLC pts to provide physicians with the information needed to make optimal treatment decisions. [Table: see text]

Non-Small Cell Lung Cancer from Genomics to Therapeutics: A Framework for Community Practice Integration to Arrive at Personalized Therapy Strategies

“…In an analysis by Gutierrez et al, BRAF NGS testing rates in 814 community site patients were reported to be 18%, similar to MET and RET NGS testing rates [67]. Other analyses demonstrated consistent rates of 12-29% [68,69,105]. Interestingly, rates of BRAF testing were shown to be as low as 0.1% in a larger analysis of 14,461 NSCLC patients treated in the community [106].…”

“…In another larger cohort of 814 community practice patients, testing rates were similarly low, with only 69% of patients who were tested for EGFR mutations, and approximately 70% of patients who tested positive received appropriate targeted therapy [67]. In a retrospective evaluation of 1,203 advanced NSCLC patients from five community oncology practices, the testing rates of EGFR were at 54% [68]. A comprehensive retrospective cohort of 191 community oncology practices with 5688 patients performed by Flatiron Health, selected patients who were tested for EGFR alterations with either broad genomic sequencing or routine-testing and identified 154 EGFR-mutated patients in the broad-based sequencing group, but reported that only 25% of these patients received appropriate EGFR-targeted therapy [69].…”

“…In a retrospective analysis of 31,483 patients with advanced NSCLC at community practices, ALK overall testing rates were 53.1% and rose to 62.1% in 2016, with 21.5% of patients who were initiated into non-targeted therapy before receiving test results [94]. Gierman et al in 2019 evaluated 1,203 advanced NSCLC patients from five community practices and results showed that only 51% of patients were tested for ALK rearrangement, with approximately 45% of actionable patients receiving targeted therapy [68]. A concurrent study of 814 community practice patients showed that only 65% were tested for ALK alterations [67].…”

“…Advances in targeted therapy and immunotherapy have lowered the costs of molecular testing, making it a viable practice in the academic sites and the community [159]. While academic sites have benefited from a close knowledge of clinical trials and novel therapies, the drive of personalized medicine has not been uniform, with the majority of patients in the community lacking appropriate testing and assignment to therapy [66][67][68][69]94,95,106,142,143,152]. This is especially concerning as the majority of patients or approximately 85% with cancer are treated in the community setting and 50% of collaborative group trial accruals occur in the community [160].…”

Updated estimates of eligibility for and response to genome-targeted oncology drugs among US cancer patients, 2006-2020

“…However, in the real-world setting, genetic testing to determine appropriate therapy is <100%. [9][10][11][12] This may have led to higher estimates than actual real-world eligibility and response, but for these analyses, we wanted to use the most generous estimates for our estimates, thus approximating the upper boundary of eligibility and response.…”