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An advanced NSCLC patient with ALK-RNF144A and HIP1-ALK fusions treated with ALK-TKI combination therapy: a case report.

ABSTRACT:

Background

Anaplastic lymphoma kinase (ALK) rearrangement is one of the most important drivers in non-small cell lung cancer (NSCLC). Despite the effectiveness to canonical 3'-ALK fusions, the clinical efficacy of ALK inhibitors in patients with complex ALK fusions, such as nonreciprocal/reciprocal translocation remains uncertain. Exploring the optimal therapeutic regimens for this subset of patients is of crucial clinical significance.

Case description

We reported a female patient diagnosed with stage IVB lung adenocarcinoma (LUAD) harboring a novel ALK-RNF144A fusion, concurrent with a Huntingtin-interacting protein 1 (HIP1)-ALK fusion and a RB1 loss-of-function variant. The patient sequentially received multiple lines of treatment with ALK-tyrosine kinase inhibitor (TKI), chemotherapy, radiotherapy and ALK-TKI combined with anti-angiogenesis. Disease progression accompanied by a squamous cell carcinoma transformation was indicated after ALK-TKI combined with anti-angiogenesis and both ALK-RNF144A and HIP1-ALK fusions were retained in the tumor. The patient was subsequently treated with a third generation ALK-TKI, lorlatinib, in combination with albumin-bound paclitaxel and anlotinib, and then achieved stable disease. The patient remained on the treatment as of the last follow-up resulting in an overall survival (OS) of more than 18 months.

Conclusions

We have reported an advanced NSCLC patient with a complex nonreciprocal/reciprocal ALK translocation containing a novel ALK-RNF144A fusion, concurrent with a RB1 loss-of-function mutation, who subsequently experienced pathological squamous cell carcinoma transformation. The combined treatment with ALK-TKI, chemotherapy, and anti-angiogenesis demonstrates clinical efficacy and may provide optional therapeutic strategies for this phenotype.

SUBMITTER: Li H

PROVIDER: S-EPMC10774998 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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An advanced NSCLC patient with <i>ALK-RNF144A</i> and <i>HIP1-ALK</i> fusions treated with <i>ALK</i>-TKI combination therapy: a case report.

Li Hui H Liu Jingjing J Lan Shaowei S Zhong Rui R Cui Yanan Y Christopoulos Petros P Schenk Erin L EL Sasaki Takaaki T Cheng Ying Y

Translational lung cancer research 20231124 12

<h4>Background</h4>Anaplastic lymphoma kinase (<i>ALK</i>) rearrangement is one of the most important drivers in non-small cell lung cancer (NSCLC). Despite the effectiveness to canonical 3'-<i>ALK</i> fusions, the clinical efficacy of ALK inhibitors in patients with complex <i>ALK</i> fusions, such as nonreciprocal/reciprocal translocation remains uncertain. Exploring the optimal therapeutic regimens for this subset of patients is of crucial clinical significance.<h4>Case description</h4>We rep ...[more]

PMID: 38205210

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