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MO16 - Prognostic and Predictive Biomarkers IV (ID 97)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Medical Oncology
- Presentations: 1
- Moderators:S. Toyooka, J.C. Yang
- Coordinates: 10/29/2013, 16:15 - 17:45, Parkside Auditorium, Level 1
MO16.04 - Analysis of HER2 amplification in non-small cell lung cancers (NSCLCs) with acquired resistance (AR) to Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) (ID 2951)
16:15 - 17:45 | Author(s): A. Wurtz
Recent studies have demonstrated the feasibility of rebiopsy in patients (pts) with EGFR mutant NSCLC at the time of AR to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib or gefitinib, and provide estimates of the prevalence of well described mechanisms of AR including the EGFR T790M mutation, MET amplification and small cell lung cancer (SCLC) transformation. HER2 amplification has also been described in cases of AR to EGFR TKIs, however, its exact frequency is still unclear. Moreover, comprehensive analysis of paired pre- and post-treatment samples to establish whether HER2 amplification is acquired during treatment with TKIs have not been performed. This prompted us to further investigate HER2 amplification in EGFR mutant NSCLC cases.
Pts with metastatic or recurrent NSCLC who developed AR while on a molecularly targeted agent were enrolled on an IRB approved repeat biopsy protocol. Tumor biopsies were obtained at the time of AR, and histopathological and molecular analyses of the tumors were performed. Known mechanisms of AR to EGFR TKIs were analyzed (T790M mutation, MET amplification and SCLC transformation) as well as amplification of HER2. The presence of T790M was assessed either by Taqman or pyro-sequencing (unless T790M status was available from an outside institution). HER2 and MET amplification were determined using fluorescence in situ hybridization (FISH).
41 pts with AR to EGFR TKIs (erlotinib or gefitinib) were enrolled at YCC between Jan 2012 and May 2013. Histological analysis of all specimens revealed transformation of adenocarcinoma to SCLC in 3 cases (7%). Depending on the availability of tissue, samples were prioritized for T790M analysis followed by MET and HER2 amplification. T790M was identified in 36% of pts; MET and HER2 amplification were found in 11% and 10% of samples respectively. In the two cases with HER2 amplification, analysis of the pre-treatment specimen revealed that amplification of this receptor tyrosine kinase preceded treatment with EGFR-TKIs, however, the amplification level was lower pre-treatment in both cases. Specifically the ratio of HER2 to CEP17 probes was 2.8 pre-treatment in both cases and increased to 4.3 and 8 following TKI treatment. HER2 amplification was mutually exclusive with the other tested mechanisms of resistance.
T790M was the most commonly identified mechanism of AR to EGFR TKIs in the YCC cohort consistent with other studies. MET amplification, HER2 amplification and SCLC transformation were also observed. The observation that HER2 was amplified pre-treatment warrants further investigation of HER2 amplification in AR and pre-treatment specimens. Whole exome sequencing of specimens without known resistance mechanisms is ongoing.
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