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Targeted Therapies for NSCLC (Adenocarcinoma) - Genomic Profiling and Therapeutic Strategies

Understand the latest treatment options for NSCLC with ALK rearrangement and ROS1 detection. Learn about key drugs, detection methods, and clinical implications presented at the 2017 ASCO Annual Meeting.

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Targeted Therapies for NSCLC (Adenocarcinoma) - Genomic Profiling and Therapeutic Strategies

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  1. NSCLC ALK-traslocato Valutazione e problematiche patologiche Massimo C.P. Barberis Unità Clinica di Diagnostica Istopatologica e Molecolare

  2. Translating Genomic Profiling Data into Therapeutic Strategies (Lung Adenocarcinoma) RET: Cabozantinib : RR=40% HER2 mutation HER2 mutation: >50% RR to Afatinib; ~20% to Dacomitinib ROS1: 70% RR to Crizotinib BRAF (V600E): >60% RR to BRAF + MEK inhibitor combo ALK: 65%RR to Crizotinib: ~70% RR to 2° Gen TKI Ceritinib in resistant cancers METex14: RR >50% to Crizotinib KRAS: 35% RR to MEK inhibitors + Chemotherapy EGFR: RR>70% to 1°-2° Gen TKIs; ~60% RR to 3° Gen TKIs in resistant cancers

  3. ALK and ROS1 detection epitomize the rapid advances being achieved in the basic science, diagnosis, and treatment of lung cancer. Three drugs (crizotinib, ceritinib, and alectinib) have become available for the treatment of ALK-rearranged lung tumors, and one drug (crizotinib) is now available for ROS1-rearranged tumors. NSCLC : ALK rearrangement prevalence 3-5% ROS1 < 2% http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm358301.pdf. Clinical role of the different fusion partners is unknown

  4. ALK Patients characteristics 70-80% 40-50 yrsneversmokers adenocarcinoma NSCLC 70 yrs EGFR mut- 60-65 yrs ALK rearrangedtumorshavebeenfound in patientsolderthan 70 yrs and youngerthan 40 yrs

  5. ALK rearrangement in NSCLC Presented By Alice Shaw at 2017 ASCO Annual Meeting

  6. Study rationale Presented By Alice Shaw at 2017 ASCO Annual Meeting

  7. Primary endpoint: PFS, investigator-assessed Presented By Alice Shaw at 2017 ASCO Annual Meeting

  8. PFS by baseline CNS metastases status* Presented By Alice Shaw at 2017 ASCO Annual Meeting

  9. Secondary endpoint: <br />Time to CNS progression (by IRC, ITT) Presented By Alice Shaw at 2017 ASCO Annual Meeting

  10. Conclusions Presented By Alice Shaw at 2017 ASCO Annual Meeting

  11. Targeted-therapy for patients with advanced NSCLC (adenocarcinomas or tumors with an adenocarcinoma component) is encouraging Molecular testing is crucial for therapy The approval of the IHC test ( clone D5F3) gives access to specific drugs in an easier way Which patients should be screened for ALK and ROS1 gene rearrangements? What is the most cost-effective screening method?

  12. Screening for ALK and ROS1 rearrangement should be done for all patients with advanced NSCLC ( adenocarcinoma or cancer with an adenocarcinoma component) Screening should be considered in patients with younger age, never/light smoking history, or negative results on testing for EGFR and KRAS mutations Currently, two assays are approved: the ALK FISH Break Apart assay and the ALK (D5F3) IHC (Ventana). In the future?

  13. NGS represents a practical and reliable ALK and ROS1 testing approach for use with routine lung cancer tissue specimens, enabling patients to receive optimal therapies. This novel methodology can also assess genomic-related mechanism of resistance to ALK-targeted therapies and guide the appropriate selection of the next generation of inhibitors.

  14. NSCLC –biopsy - H&E IHC FISH MolecularTesting

  15. a b c • EBUS-TBNA • DiffQuick stain (R.O.S.E.) • H&E from cyto-block • Anti TTF-1 from cytoblock

  16. Criteria of acquired resistance to TKIs in NSCLC (. Modified Criteria of acquired resistance to TKIs in NSCLC from Jackman et al.6) Jackman D, Pao W, Riely GJ et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010;28;357-360.

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