2024 World Conference on Lung Cancer (WCLC) - ePosters-EP.12B.12 Intrinsic ALK-TKI Resistance Due to Met-Coamplification in ALK+ NSCLC, Effectively Treated by Alectinib-crizotinib Combination

EP.12B.12 Intrinsic ALK-TKI Resistance Due to Met-Coamplification in ALK+ NSCLC, Effectively Treated by Alectinib-crizotinib Combination

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This case report discusses the unique scenario of intrinsic resistance to ALK-TKI treatment due to MET-coamplification in a patient with ALK-rearranged non-small cell lung cancer (NSCLC). Typically, patients with advanced ALK-rearranged NSCLC respond well to second-generation (2G) ALK-TKIs. However, the report details a rare case where intrinsic resistance was observed due to a de novo MET-amplification, presenting a previously underrecognized resistance mechanism.<br /><br />The patient, a 46-year-old female non-smoker with T4N3M1c lung adenocarcinoma, began treatment with Brigatinib, a 2G ALK-TKI. Despite expectations, her response was suboptimal after three months, and progression occurred at six months. A re-biopsy of a hepatic metastasis confirmed continued ALK fusion and TP53 mutation, coupled with MET receptor overexpression and high-level MET amplification.<br /><br />While MET-amplification is a known cause of acquired resistance to ALK-TKIs, in this case, it was identified as an intrinsic factor, present but undetected in initial diagnostics. The biopsy showed high MET expression and amplification, which were not initially captured by next-generation sequencing (NGS).<br /><br />Upon discovering the intrinsic MET-amplification, the treatment strategy was revised to include a combination of Alectinib, an ALK inhibitor effective against the EML4-ALK fusion variant, and Crizotinib, a MET-TKI. This combination therapy led to a significant improvement in the patient's condition, demonstrating its efficacy and safety over nine months.<br /><br />This case underscores the need for thorough diagnostic evaluations to detect possible MET amplifications that contribute to intrinsic resistance, advocating for the use of FISH in NGS-negative cases. The successful use of combined therapy with Alectinib and Crizotinib offers a promising alternative approach for similar ALK NSCLC cases resistant to traditional ALK-TKI treatments.

Asset Subtitle

Edyta Urbanska

Meta Tag

Speaker Edyta Urbanska

Topic Metastatic Non-small Cell Lung Cancer – Targeted Therapy

Keywords

ALK-rearranged NSCLC

MET-coamplification

intrinsic resistance

Brigatinib

Alectinib

Crizotinib

ALK-TKI treatment

MET-amplification

combined therapy

diagnostic evaluations