Crizotinib Re-Challenge Overcomes Multiple Resistant Clones in cMET Positive NSCLC Patient

Case Report

Volume 2, Issue 3 (August Issue)

Crizotinib Re-Challenge Overcomes Multiple Resistant Clones in cMET Positive NSCLC Patient

Walid Shalata^1,2*, Roni Gillis^1,2*, Waleed Kian^1,2, Michal Goldhirsh^1,2, Aharon Yehonatan Cohen^1,2, Roxana Denisa Grinberg^1,2, Dina Levitas^1,2, Lior Soussan Gutman³, Addie Dvir³, Steve Olsen⁴, Richard B. Lanman⁴, Laila C. Roisman² and Nir Peled^1,2

¹Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel

²The Legacy Heritage Center and Dr. Larry Norton Institute, Soroka Medical Center, Beer Sheva, Israel

³Oncotest-Teva / GUARDANT Health

⁴Guardant Health, Inc., Redwood City, California, USA

*Corresponding author: Walid Shalata, MD, Resident Physician of Oncology, The Legacy Heritage Oncology Center and Dr. Larry Norton Institute, Soroka Medical Center and Ben-Gurion University, Beer-Sheva, Israel, Tel: +972 (0)542967100; Email: walid.shalata@gmail.com

Received: May 28, 2020; Accepted: June 10, 2020; Published: July 04, 2020

Citation: Walid S, Roni G, Waleed K, et al. Crizotinib Re-Challenge Overcomes Multiple Resistant Clones in cMET(+) NSCLC Patient. Clin Image Case Rep J. 2020; 2(3): 118.

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Crizotinib Re-Challenge Overcomes Multiple Resistant Clones in cMET Positive NSCLC Patient

Abstract

Objectives: Non-Small Cell Lung Carcinomas (NSCLC) presents mesenchymal-epithelial transition factor exon 14 skipping (METex14) mutation in 0.6-7 % of patients. Crizotinib is a Tyrosine Kinase Inhibitor (TKI) that has been approved for the treatment of ALK-rearranged tumors and demonstrated clinical activity in MET(+) NSCLC. Acquired point mutations in the MET gene have been described as mechanisms of resistance to crizotinib.

Materials and Methods: For the evaluation of the MET clones we have used cell-free DNA (cfDNA) NGS test (Guardant360).

Results: In this report, we present a 66-year-old previously healthy non-smoking male who was diagnosed with metastatic adenocarcinoma of the lung with METex14 mutation, PDL-1 expression more than 50 %. The patient developed multiple secondary c-MET resistant clones and responded to re-exposure to crizotinib therapy.

Conclusion: According to this case we suggest that clonal evolution is not necessarily a synonymous with resistant to previous lines (beyond the recent one). Similar phenomenon was previously reported in an ALK fusion case with respond to crizotinib re-exposure, by Shaw et al. The eradication of the emerging clones by crizotinib, as presented in this case, may support this assumption and suggest cautious re-exposure to previous lines in case of emerging resistant. Hypothetically, if this is not the case, we may suggest that crizotinib has changed the microenvironment in a way allowing eradication of the different clones by the activated immune system, however we do not have any support for this assumption.

Keywords: Targeted therapy; Non-small cell lung carcinoma (NSCLC); c-MET Acquired resistance; Crizotinib