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Plasma, urine genotyping effectively identify mutations in NSCLC
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CHICAGO — Patients with T790M–positive non–small cell lung cancer had similar responses to rociletinib whether their mutation status was determined by tissue, urine or plasma genotyping, according to data presented at the ASCO Annual Meeting.
However, plasma and urine testing identified epidermal growth factor receptor mutations missed by biopsy, due to tumor heterogeneity or inadequate sample quality, results showed.
Heather A. Wakelee
“With third-generation tyrosine kinase inhibitors targeting EGFR, which primarily work in the setting of the T790M resistance mutation, it is important to determine the best way to identify the mutation,” Heather A. Wakelee, MD, associate professor of medicine–oncology at Stanford University Medical Center, told HemOnc Today. “Our analysis showed that detection was similar across assays, but not entirely overlapping, suggesting that the tests can complement each other.”
Rociletinib (Clovis Oncology) is an oral inhibitor of mutant EGFR, including T790M mutations.
Wakelee and colleagues evaluated the presence of the EGFR mutation in circulating tumor DNA detected in blood and urine samples compared with matched tissue samples from the phase 1/2 TIGER-X study, which evaluated rociletinib in patients with EGFR–positive advanced NSCLC.
The researchers used the therascreen EGFR test (Qiagen) to assess tissue samples, BEAMing (Sysmex) to test plasma, and a quantitative short footprint assay method using next-generation sequencing (Trovagene) to test urine samples.
The trial had a safety population of 548 patients (median age, 63 years; 20.6% Asian individuals) and an efficacy population of 443 patients. The researchers had access to 540 tissue specimens, 482 plasma specimens and 213 urine specimens available for EGFR testing.
Using tissue as a reference, plasma genotyping identified T790M mutations with a sensitivity of 80.9%. Plasma testing identified 374 patients positive for mutations, compared with 387 patients identified through tissue.
Urine genotyping detected mutations with a sensitivity of 81.1%, with 169 T790M–positive patients identified by urine detection and 175 patients detected through tissue.
Among 181 patients for whom all three samples were available, 174 were found to be T790M–positive by at least one assay, with 57% (n = 104) positive by all three. Seven patients in this subset were found negative by all assays.
The investigator-confirmed overall response rate in the entire cohort was 33.9%.
Four patients out of 14 who tested positive for T790M in plasma but negative in tissue responded to rociletinib, as did three patients out of seven who tested positive in urine but not in tissue.
Shrinkage of the target lesions correlated with higher T790M–activating mutation ratio in plasma (P = .006).
“Does this mean that T790M found by one way differs from T790M found another way?” Wakelee said during her presentation. “At least by looking at the confirmed ORR by investigators, the answer to that is no.”
The most common adverse events included hyperglycemia, diarrhea, nausea and fatigue.
“Though rociletinib is no longer in development, our findings have implications for other TKIs that work against T790M,” Wakelee said. “The hope is that we will have plasma and urine testing available for patients so that we can avoid invasive biopsies for most patients in the future. The utility of these tests can eventually be expanded beyond EGFR and T790M.” – by Cameron Kelsall
Reference:
Wakelee HA, et al. Abstract 9001. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Wakelee reports institutional research funding and travel expenses from Clovis Oncology, as well as honoraria, travel expenses and research funding from, and consultant roles with, multiple pharmaceutical companies. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Grace Dy, MD
This prospective study adds to the growing scientific evidence supporting the use of “liquid biopsy” sources, such as plasma and urine testing, for analytically validated tests in terms of tumor mutation profiling. This abstract showed that the outcomes to treatment using a third-generation EGFR tyrosine kinase inhibitor was similar regardless of the platform of testing (ie, EGFR T790M mutation status determination in tissue vs. plasma and/or urine).
Liquid biopsy assays provide a complementary, and on occasion, the only potential feasible way, of documenting mutation status to direct treatment decisions. Indeed, FDA recently approved the use of the blood-based Cobas EGFR mutation test v2 diagnostic test (Roche Molecular Diagnostics) to detect specific mutations in EGFR for patients with non–small cell lung cancer. Many other platforms with a more comprehensive panel have undergone or are undergoing clinical validation. It is anticipated that there will be increased utilization of such tests, particularly in patients with tumors that are not feasible to conventional percutaneous biopsy or tumor excision.
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