The article "Efficacy of Incremental Next-Generation ALK Inhibitor Treatment in Oncogene-Addicted, ALK-Positive, TP53-Mutant NSCLC" presents a case study of a patient with advanced non-small cell lung cancer (NSCLC) that was positive for the ALK fusion gene and had a TP53 mutation, which is associated with poor prognosis. The patient was initially treated with the ALK inhibitor crizotinib but developed resistance to the treatment. The patient then underwent genomic testing, which identified a secondary ALK mutation that was potentially targetable by the next-generation ALK inhibitor alectinib. The patient was treated with alectinib and showed a partial response to the treatment, but then developed resistance to alectinib as well. Genomic testing identified a third ALK mutation that was potentially targetable by the next-generation ALK inhibitor lorlatinib. The patient was treated with lorlatinib and showed a durable partial response to the treatment.

Key Takeaways:

• The article describes a case study of a patient with advanced non-small cell lung cancer (NSCLC) that was positive for the ALK fusion gene and had a TP53 mutation, which is associated with poor prognosis.
• The patient was initially treated with the ALK inhibitor crizotinib but developed resistance to the treatment.
• Genomic testing identified secondary and tertiary ALK mutations that were potentially targetable by next-generation ALK inhibitors alectinib and lorlatinib, respectively.
• Incremental next-generation ALK inhibitor treatment with alectinib and lorlatinib led to a partial response to the treatment and durable disease control in the patient.
• This case study highlights the potential of genomic testing and targeted therapy with next-generation ALK inhibitors for NSCLC patients with ALK-positive tumors and TP53 mutations, which is a poor prognostic factor.
• Incremental next-generation ALK inhibitor treatment may provide a therapeutic option for NSCLC patients who develop resistance to initial ALK inhibitor treatment.

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‍Urbán L, Dóczi R, Vodicska B, Kormos D, Tóth L, Takács I, Várkondi E, Tihanyi D, Lakatos D, Dirner A, Vályi-Nagy I, Peták I.
J Pers Med. 2020 Aug 28;10(3):107. doi: 10.3390/jpm10030107. PMID: 32872120; PMCID: PMC7563786.

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