EGFR Mutation Companion Diagnostic Test Receives Korean Approval in NSCLC
Approval of the Droplex EGFR Mutation Test v2 may improve access to appropriate targeted therapies for patients with EGFR-mutated non–small cell lung cancer in Korea.
The Droplex EGFR Mutation Test v2 is a digital polymerase chain reaction (PCR)–based in-vitro diagnostic test that demonstrates significantly higher sensitivity compared with other EGFR mutation tests that use reverse transcription PCR (RT-PCR).
The Korean Ministry of Food and Drug Safety has approved the Droplex EGFR Mutation Test v2 as a companion diagnostic for detecting EGFR mutations in patients with non–small cell lung cancer (NSCLC) and guiding appropriate treatment decision making for those with detected mutations, according to a press release from Gencurix.1
According to its manufacturers, the Droplex EGFR Mutation Test v2 is a digital polymerase chain reaction (PCR)–based in-vitro diagnostic test that demonstrates significantly higher sensitivity compared with other EGFR mutation tests that use reverse transcription PCR (RT-PCR). The developers indicate that the test was designed to detect a maximum of 107 mutations.
The digital PCR-basted test is also capable of detecting exon 20 insertion mutations, which the press release described as something that no existing single gene tests in the country are able to properly detect. In addition to the Droplex EGFR Mutation Test v2, manufacturers have received European CE certification for other tests that detect KRAS, BRAF, C-MET, PIK3CA, ESR1, and POLE mutations.
According to the press release, manufacturers plan to research early cancer detection and screening for minimal residual disease through digital PCR technology.
Investigators previously compared a droplet digital PCR–based EGFR (ddEGFR) test and a cobas EGFR test for detecting EGFR mutations in NSCLC formalin-fixed paraffin-embedded tissue (FFPET) DNA samples as part of a retrospective comparative clinical study published in Scientific Reports.2 Across 316 NSCLC FFPET samples, the ddEGFR and cobas EGFR test methods yielded a positive percent agreement (PPA) of 94.04%, a negative percent agreement (NPA) of 63.41%, and an overall percent agreement (OPA) of 78.10%.
After applying an internal control index (iQC) index criterion to the 316 FFPET samples, investigators re-classified 150 samples into group 3, in which the IQC criteria were satisfied. Re-analyzing the concordance rates between ddEGFR and cobas EGFR test results in this group of samples yielded a PPA of 100.0%, a NPA of 75.0%, and an OPA of 92.67%. Among samples in group 4, in which the iQC criteria were not satisfied, the respective concordance rates were 78.57%, 58.20%, and 63.41% between the 2 EGFR testing methods. The data suggested that the iQC index was critical in determining whether DNA was of sufficient quality for the ddEGFR test, according to investigators.
In an analysis of 11 discordant samples in group 3, investigators performed macrodissection for each tumor tissue sample before re-analyzing EGFR mutations among 8 samples; this produced negative results with cobas EGFR testing and positive results with ddEGFR testing. Following macrodissection, the cobas EGFR test yielded the same results as the ddRGFR test for 4 of 8 samples, suggesting that the latter demonstrated greater sensitivity in detecting EGFR mutations independent of tumor ratio.
“Our ddPCR-based EGFR mutation test exhibited superior analytical performance to the cobas EGFR test,” the study authors wrote. “A future clinical study should evaluate the use of the ddPCR-based EGFR test to determine the suitability of patients [with NSCLC] for EGFR-[tyrosine kinase inhibitor] treatment in cases in which the cobas EGFR test reports no mutation.”
In this retrospective study, investigators collected and analyzed NSCLC FFPET-DNA samples of various ages and qualities across 3 sites. Additionally, they formed cut-offs of ddEGFR test results based on false-positive analyses using FFPET samples to account for false positive reports due to the test’s intrinsically high sensitivity.
References
- Gencurix obtains approval for companion diagnostic of digital PCR-based EGFR mutation test. News release. Gencurix. June 13. 2023. Accessed June 15, 2023. bit.ly/42HbThC
- Kim SS, Choi HJ, Kim JJ, et al. Droplet digital PCR-based EGFR mutation detection with an internal quality control index to determine the quality of DNA. Sci Rep. Published online January 11, 2018. doi:10.1038/s41598-017-18642-x
