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Lung Cancer Research Studies / Lung Cancer Treatments and Mutations · Journal article
Frontiers in Pharmacology · August 18, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a single-case report describing clinical and radiological response to a three-drug regimen (lorlatinib, dual chemotherapy, and bevacizumab) in a patient with ALK-positive lung adenocarcinoma who had progressed on iruplinalkib. The patient developed marked remission of malignant pleural effusion after treatment modification, but this represents one patient's experience and cannot be generalized without further evidence.
Single-patient case report. One 38-year-old male with stage IV lung adenocarcinoma carrying EML4-ALK V5' fusion variant.. Intervention: Lorlatinib 100 mg once daily combined with cisplatin and pemetrexed chemotherapy plus bevacizumab anti-angiogenic therapy.. n = 1.
38-year-old male with stage IV EML4-ALK V5' fusion lung adenocarcinoma (4% of EML4-ALK cases) Initial progression on iruplinalkib 180 mg daily after 6.3 months with development of substantial malignant pleural effusion Marked remission of malignant pleural effusion observed following switch to lorlatinib 100 mg daily combined with cisplatin, pemetrexed, and bevacizumab
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This case suggests a potential treatment strategy for ALK-positive NSCLC patients with acquired resistance to second-generation TKIs, specifically the rare V5' variant. However, clinical decision-making should not be based on a single case; further prospective data are needed to establish efficacy and safety of this three-drug combination.
Single-case report of a treatment strategy in a rare ALK variant; describes clinical response but lacks control group, quantified endpoints, or generalizable evidence.
As stated by the source record.
Quoted from the source exactly as published.
This case suggests a potential treatment strategy for ALK-positive NSCLC patients with acquired resistance to second-generation TKIs, specifically the rare V5' variant. However, clinical decision-making should not be based on a single case; further prospective data are needed to establish efficacy and safety of this three-drug combination.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Background The Echinoderm microtubule-associated protein-like 4 (EML4) - Anaplastic lymphoma kinase (ALK) gene fusion represents a significant driver mutation in non-small cell lung cancer (NSCLC). Among the over 20 identified EML4-ALK variant subtypes, the V5' variant occurs relatively infrequently, constituting merely 4% of cases. Currently, the clinicopathological features and prognostic implications associated with this particular variant remain poorly characterized in the literature. Case summary We report the case of a 38-year-old man diagnosed with stage IV lung adenocarcinoma carrying the EML4-ALK V5' fusion variant, who received first-line treatment with iruplinalkib at a dose of 180 mg once daily. After 6.3 months of therapy, the patient developed a substantial malignant pleural effusion. Consequently, the treatment regimen was switched to lorlatinib 100 mg once daily combined with intrathoracic infusion chemotherapy. However, no significant improvement in the malignant pleural effusion was observed. We thereafter modified the therapeutic strategy to include lorlatinib-based targeted therapy combined with a dual-agent chemotherapy regimen consisting of cisplatin and pemetrexed, along with bevacizumab for anti-angiogenic therapy. Following this adjustment, the patient’s malignant pleural effusion showed marked remission. Conclusion For patients with NSCLC harboring the EML4-ALK V5' fusion variant who have developed resistance to second-generation tyrosine kinase inhibitors (TKIs), switching to third-generation TKI lorlatinib in combination with chemotherapy and anti-angiogenic treatment may serve as a potential therapeutic option for overcoming acquired resistance and curbing rapid disease progression.
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