TEST:

Oncomine™ Dx Target Test

We report a rare case of selpercatinib use for MMFCC. Since RET mutations may occur frequently in MMFCC, selpercatinib could be effective in treating MMFCC.

The AmoyDx PLC panel, a PCR-based multiplex diagnostic test, exhibits a high success rate. The frequency of the nine genes targeted for treatment detected by the AmoyDx PLC panel was comparable to the frequency of mutations detected by ODxTT-M. Clinicians should understand and use the AmoyDx PLC panel and ODxTT-M with respect to their respective performances and limitations.

"Bayer AG and Thermo Fisher Scientific Inc...announced to develop next-generation sequencing (NGS)-based companion diagnostic assays (CDx) together. These will help identify patients who may benefit from Bayer’s growing portfolio of precision cancer therapies by offering decentralized genomic testing and rapid turnaround time...The CDx will be developed using Thermo Fisher’s Oncomine Dx Express Test on the Ion Torrent Genexus Dx System, a fully integrated NGS platform that can deliver results on a patient’s tumor or liquid biopsy sample in as little as 24 hours."

This study highlights the benefits of combining morphological and immunohistochemical analyses for gene detection and posits that lymph node metastases are more suitable for genetic analysis owing to their mild calcification. Our results emphasize the importance of accurate sample processing in diagnosing and treating thyroid carcinomas.

Even if sufficient tumor samples are obtained, rare EGFR mutations (which are excluded from the ODxTT's genetic mutation list) might not be detected using the current ODxTT system due to the program used for sequence analysis. However, such rare EGFR mutations can still be accurately detected on ODxTT's sequence data using next-generation sequencing.

The 6 AV studies met the necessary product requirements and acceptance criteria to detect clinical samples with ERBB2 mutations. Additionally, the CV study clinical accuracy and clinical efficacy results demonstrated the safety and effectiveness of the use of the ODxTT in FFPE samples as an aid to identify NSCLC patients eligible for treatment with the Daiichi Sankyo lung cancer therapeutic T-DXd.

On September 29, 2023, the FDA granted companion diagnostic approval to the Oncomineâ„¢ Dx Target Test (ODxT Test) as an aid in the selection of patients with BRAF V600E-mutated ATC who may be eligible for treatment with dabrafenib in combination with trametinib. The ODxT Test was shown to be effective in identifying BRAF V600E mutations in ATC patients through a clinical concordance study using specimens from patients enrolled in the ROAR trial and commercially-sourced samples. The results support the expanded indication to the ODxT Test and marks the first FDA-approved NGS-based companion diagnostic for patients with BRAF V600E-mutated ATC.

These findings suggest that while both CDx tests are effective in detecting almost all actionable EGFR mutations, ODxTT provides slightly broader coverage. These results emphasize the importance of selecting appropriate CDx tests to inform treatment decisions for EGFR-positive NSCLC patients.

Multivariate logistic regression analysis identified ddCq and ΔCq as significant predictors of DNA and RNA NGS success rates, respectively. Quality assessment of nucleic acid extracted from archival tissue samples is important for achieving high NGS success rates in clinical practice, especially for samples ≥3 years old.

This study shows a clear difference between AD and NFAD in terms of cancer progression, pathological features of the main tumor, genetic characteristics, and PD-L1 expression.

Furthermore, genetic mutations were detected in 39 of 112 cases (35 %) in group A and 59 of 102 cases (58 %) in group B, which was statistically higher in group B (P = 0.0006). Genetic mutations were detected in 45 of 55 adenocarcinoma cases in group B. The genetic mutations detected in epidermal growth factor rescepor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), and mesenchymal epithelial transition (MET) were higher in group B. Increasing the number of tumour cells and tumour content can enhance the detection rate of genetic mutations using ODxTT.

No abstract available

Conclusions The success rate of ODxTT on EBUS-TBNA specimens were 90%. It is expected to yield specimens of sufficient quality and quantity to perform ODxTT and may be an important diagnostic option in lung cancer cases with enlarged lymph nodes.

The patient was treated with osimertinib after progression on chemoradiotherapy followed by durvalumab, and a partial response was maintained for more than 20 months. To predict EGFR-TKI efficacy, confirmation of gene mutations and VAF using next-generation sequencing is helpful.

Overall, these findings suggest that the slow-pull method is a superior technique for EBUS-TBNA to obtain high-quality tissue samples for NGS. The slow-pull method may contribute to the identification of driver gene mutations and translocations and facilitate personalized treatment of NSCLC.

However, among the other three discordant cases harboring the mutations reportable by the ODxTT, only one patient had a clinical response with short duration. Among the discordant cases for common EGFR mutations between the ODxTT and the conventional single gene test, there are a certain number of suitable patients responsive to EGFR-TKIs, especially when the cause of the discordant results comes from the difference in the range of detectable variants that are reportable between the tests.

Our findings indicate that a TS of ≥4000 is a feasible and relevant criterion for ODxTT testing, and its adoption should help to improve the success rate of such testing in clinical practice.

[Conclusion] The concordance rate of multi-gene testing to single-gene testing tended to be poor for some genes. The prognosis for Driver+ patients without targeted therapy was not different from that for Driver- patients and could be improved with appropriately performed biomarker testing and the initiation of targeted therapies.

ODxTT was able to detect driver mutations in 58.5% of cases. However, there were some cases where the results of the ODxTT and EGFR clamp assays diverged for detecting EGFR mutations. The reasons for unsuccessful ODxTT testing could be problems with sample quantity or nucleic acid quality or the sequencing analysis program failed to detect rare variants.

This study investigated the distribution of EGFR E20ins in the Asian population, with p.A767_V769dup and p.S768_D770dup being the most frequently observed mutations. Since some studies have reported single EGFR E20ins sequences using different names, it is important to be cautious when describing EGFR E20ins. To ensure comprehensive coverage in real-world settings, each method used for the detection of EGFR E20ins must be annotated according to the HGVS nomenclature.

False positives for exon 20 insertion may occur when using cobas EGFR, and false negatives for exon 19 deletion and L858R mutations may occur when using ODxTT.

DNA concentration and degree of RNA degradation are key factors determining the success of diagnostic testing by the ODxTT.

NERoNE evaluates data from NGS profiling of three OU mapping key actionable molecular alterations in a large population of aNSCLC also accounting for PDL1 status. This preliminary analysis will be the starting point for further evaluations in order to improve the personalized approach to aNSCLC. >*For 15 pts PDL1 expression was not known.

This study demonstrates the analytical and clinical accuracy of the ODxT Test as a CDx for detecting activating HER2 mutations in NSCLC to identify pts who may benefit from T-DXd. A high level of agreement was also shown between the ODxT Test and CTAs. Clinical trials for HER2m NSCLC may successfully use a central testing assay as a CDx while allowing adequately validated local testing assays to expedite patient enrollment.

No abstracts available

TTT was decreased from 29 to 22 days with ODxTT, in contrast with single biomarker tests (median, 21-23 days overall). These results indicate that biomarker testing frequency has changed in Japanese clinical practice during the study and that the use of ODxTT has increased over time, which potentially contributed to the shortening of TTT.

The success rate of ODTT testing improved after the introduction of ROSE and the implementation of the test at their facility.

The Results of implementation rate of biomarker testing, and analysis Results of factors related to the success rate of biomarker testing will be reported at this meeting. We hope that the Results of this study would contribute to the establishment of a system where all patients with lung cancer can receive appropriate personalized medicine.

We are currently collecting information on treatment and prognosis, and the rate of induction of systemic therapy and the proportion of patients receiving each targeted therapy drug based on each biomarker will be reported at this meeting. We hope that the results of this study would contribute to the establishment of a system where all patients with lung cancer can receive appropriate personalized medicine.

The success rate of ODxTT is slightly inferior to that of cobas EGFR. ODxTT shared a high concordance rate and k-coefficient with cobas EGFR in detecting EGFR mutations, but discordant results between the two tests were observed in a few cases, mainly due to the difference of detectable EGFR variants.

"The U.S. Food and Drug Administration (FDA) has granted approval to Thermo Fisher Scientific’s Oncomine Dx Target Test as a companion diagnostic (CDx) to aid in selection of patients with RET-fusion positive locally advanced or metastatic non-small cell lung cancer (NSCLC), RET-fusion positive advanced or metastatic thyroid cancer and RET-mutation positive advanced or metastatic medullary thyroid cancer (MTC) who may be eligible for treatment with Lilly’s Retevmo (selpercatinib)."

"On September 21, 2022, the Food and Drug Administration granted regular approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test...FDA also approved the Oncomine Dx Target (ODxT) Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib."

P1; Overall response rates were comparable between the CHRYSALIS, Guardant360 CDx, and ODxT Test populations. Both plasma-based and tissue-based diagnostic tests provided accurate, comprehensive, and complementary approaches to identifying patients with EGFR ex20ins who could benefit from amivantamab therapy.

"Food and Drug Administration granted accelerated approval to fam-trastuzumab deruxtecan-nxki (Enhertu, Daiichi Sankyo, Inc.) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC)...FDA also approved the Life Technologies Corporation’s Oncomine™ Dx Target Test (tissue) and the Guardant Health, Inc.’s Guardant360® CDx (plasma) as companion diagnostics for Enhertu."

Thus, we proposed the pathological criteria for accurate ODxTT. Our result suggested that tumor cell proportions of less than 20% (around 5%) could be applicable for ODxTT. We hope that our results will help pathologists to choose between the multi-plex test (ODxTT) or single-plex test in routine diagnostics.

One of the selective oral MET inhibitors, tepotinib, is only used in Japan when METex14skipping is detected by ArcherMET, a next generation sequencer... The discrepancies observed between these systems may be owing to low allele frequencies. More analysis for these are warranted.

The analysis of ODxTT for specimens biopsied using only small forceps is prone to be unsuccessful due to an insufficient amount of nucleic acid.

Chest physicians should be noted that there might be rapidly progressive fatal patients among those with MET exon 14 skipping mutations.

CT and EBUS findings were not associated with successful NGS. Bronchoscopists should obtain sufficient core tissues for successful NGS using EBUS-TBNA specimens.

"The U.S. Food and Drug Administration (FDA) has granted premarket approval to Thermo Fisher Scientific's Oncomine Dx Target Test as a companion diagnostic (CDx) to help identify non-small cell lung cancer (NSCLC) patients whose tumors carry epidermal growth factor receptor (EGFR) Exon20-insertion mutations for potential treatment with RYBREVANT^® (amivantamab-vmjw)*, Janssen Biotech, Inc.'s (Janssen's) targeted therapy."

Multivariate analysis revealed a significant difference for surgical resection alone (p = 0.006, 95% CI; 1.36 to 6.18, odds ratio, 2.90). Although the success rate of genetic alteration testing immediately after Oncomine DxTT induction was not sufficient in this study, optimizing specimen quantity and quality may improve the use of driver gene testing in clinical settings.

Clinical trials in NSCLC initiated over the past 5 years have consistently included CGP-specific genes or markers in eligibility criteria. Patients with NSCLC have the potential to benefit from the use of CGP as compared to smaller gene panels through improved access to clinical trials.