Case report: first-line lorlatinib in metastatic lung adenocarcinoma with a novel WIPF1-ALK and EML4-ALK dual fusion
Case Report

Case report: first-line lorlatinib in metastatic lung adenocarcinoma with a novel WIPF1-ALK and EML4-ALK dual fusion

Sili Wang1#, Xinxin Chen1#, Yangyang Ma1, Qiuyuan Xia2, Dongmei Yuan1, Tangfeng Lv1, Yanwen Yao1

1Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China; 2Department of Pathology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China

Contributions: (I) Conception and design: Y Yao, S Wang; (II) Administrative support: Y Yao, T Lv; (III) Provision of study materials or patients: D Yuan, Y Yao; (IV) Collection and assembly of data: X Chen, Y Ma; (V) Data analysis and interpretation: Y Yao; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

#These authors contributed equally to this work.

Correspondence to: Yanwen Yao, MD, PhD; Tangfeng Lv, MD, PhD; Dongmei Yuan, MD, PhD. Department of Respiratory and Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 305 Zhongshan East Road, Xuanwu District, Nanjing 210002, China. Email: aliceyao1112@163.com; bairoushui@163.com; yuandongmei.1@163.com.

Background: The clinical management of non-small cell lung cancer (NSCLC) harboring rare anaplastic lymphoma kinase (ALK) fusion variants and complex molecular profiles remains challenging. Herein, we report, for the first time, a case of NSCLC with concurrent novel WAS/WASL interacting protein family member 1 (WIPF1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK double fusions, along with a concomitant TP53 mutation, which demonstrated marked sensitivity to lorlatinib in this genomically complex setting.

Case Description: A 57-year-old Chinese female was diagnosed with stage IVA (T4N2M1a) lung adenocarcinoma. Comprehensive genomic profiling (CGP) identified dual ALK rearrangements: a novel WIPF1-ALK fusion as the predominant oncogenic driver [variant allele frequency (VAF) 7.81% in pleural effusion] and a minor EML4-ALK fusion component (VAF 0.64% in pleural effusion). The case was further complicated by a concurrent TP53 p.R110L mutation, representing a rare co-occurrence of dual ALK fusions with an additional resistance-associated genomic alteration. The efficacy of lorlatinib as first-line therapy achieved a partial response (PR). Notably, sustained disease control had been achieved for over 24 months in this patient.

Conclusions: This report provides the first evidence of sustained efficacy of lorlatinib in a patient harboring the rare WIPF1-ALK fusion, a dual ALK rearrangement pattern, and a concurrent TP53 mutation. The achievement of over 24 months of disease control underscores lorlatinib’s potent activity against these complex molecular profiles. Our findings highlight the importance of recognizing and targeting rare ALK fusion variants—even when coexisting with other ALK rearrangements and resistance—associated mutations and expand the therapeutic landscape of precision oncology for advanced NSCLC.

Keywords: Case report; anaplastic lymphoma kinase (ALK); WAS/WASL interacting protein family member 1 (WIPF1); echinoderm microtubule-associated protein-like 4 gene (EML4); non-small cell lung cancer (NSCLC)

Submitted Jan 29, 2026. Accepted for publication Apr 04, 2026. Published online May 26, 2026.

doi: 10.21037/tlcr-2026-1-0129

Highlight box

Key findings

• This is a case report on a metastatic lung adenocarcinoma harboring a novel WAS/WASL interacting protein family member 1 (WIPF1)-anaplastic lymphoma kinase (ALK) and echinoderm microtubule-associated protein-like 4 gene (EML4)-ALK double-fusion along with a concomitant TP53 mutation, which achieved a progression-free survival exceeding 24 months with complete radiological remission following first-line lorlatinib therapy.

What is known and what is new?

• ALK rearrangements are established oncogenic drivers in non-small cell lung cancer (NSCLC), with EML4-ALK being the most prevalent. Lorlatinib has demonstrated broad efficacy against various ALK variants and retains activity in the presence of certain concomitant mutations, such as TP53.

• This is the first report describing the co-existence of WIPF1-ALK and EML4-ALK double-fusion. Comprehensive genomic profiling (CGP) revealed WIPF1-ALK as the dominant driver clone (with a high variant allele frequency of 7.81% in pleural effusion). Furthermore, this case provides the first clinical evidence that lorlatinib confers profound and durable disease control in this genomically complex setting characterized by dual ALK rearrangements and a concurrent TP53 resistance-associated mutation.

What is the implication, and what should change now?

• This case highlights the necessity of CGP to identify rare and complex driver mutations, such as dual ALK fusions with TP53 co-mutations. It supports the use of lorlatinib as a first-line therapy in this setting, demonstrating that even rare driver alterations can be effectively targeted. Further research is needed to understand the therapeutic implications of different ALK fusion variants.

Introduction

Lung cancer still remains the leading cause of cancer-related mortality globally, with non-small cell lung cancer (NSCLC) accounting for the majority of cases. Tyrosine kinase inhibitor (TKI)-based targeted therapy has been well established to significantly improve progression-free survival (PFS) and overall survival (OS) in NSCLC patients harboring actionable genetic mutations. Among these mutations, anaplastic lymphoma kinase (ALK) gene rearrangement is detected in approximately 4–5% of NSCLC patients. Epidemiological evidence indicates that ALK-positive NSCLC patients often present with advanced disease at the time of diagnosis (1,2), highlighting the urgent need for effective therapeutic strategies to enhance their survival outcomes. In recent years, targeted therapy for ALK gene rearrangements has undergone remarkable advancement (3,4). Specifically, data from the CROWN trial demonstrated that lorlatinib, a third-generation ALK TKI, significantly prolonged PFS in NSCLC patients with ALK fusion mutations (5). To date, more than 90 distinct ALK rearrangements have been identified in lung cancer (6). Among these, the EML4-ALK fusion is the most prevalent, and over 50 fusion partners are considered therapeutically tractable with ALK TKIs (7). However, double ALK fusions remain extremely rare, and the optimal standard of care for such cases remains undefined. Herein, we report a case of a NSCLC patient harboring a novel WAS/WASL interacting protein family member 1 (WIPF1)-ALK and echinoderm microtubule-associated protein-like 4 (EML4)-ALK double fusion who exhibited significant sensitivity to first-line lorlatinib therapy. We present this article in accordance with the CARE reporting checklist (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0129/rc).

Case presentation

A 57-year-old Chinese female with no significant past medical history presented to Jinling Hospital with complaints of cough and expectoration. Chest computed tomography (CT) revealed right-sided pleural effusion and pericardial effusion (Figure 1). Cytopathological examination of the pleural fluid was suspicious for adenocarcinoma, prompting additional cell block analysis (Figure 2,3). Combined with findings from abdominal CT, brain magnetic resonance imaging (MRI), and bone scintigraphy emission computed tomography (ECT), the final diagnosis was stage IVA (T4N2M1a) lung adenocarcinoma. Abnormal coagulation parameters were noted, and subsequent CT pulmonary angiography (CTPA) confirmed multiple pulmonary emboli (PE) (Figure 4A). Given the high suspicion for cancer-associated thrombosis (CAT), further evaluations were performed, including repeat coagulation studies, electrocardiography (ECG), echocardiography, and lower extremity venous Doppler ultrasonography. Therapeutic anticoagulation was initiated with low-molecular-weight heparin (LMWH), followed by transition to oral rivaroxaban for maintenance therapy. To guide precision treatment, synchronous DNA-based next-generation sequencing (NGS) was performed on the pleural fluid supernatant, cell block, and peripheral blood. The results identified two distinct ALK rearrangements: a novel WIPF1-ALK (W6:A15) fusion (not previously reported in the literature) and an EML4-ALK (E6:A17) fusion. Additional concurrent genomic alterations included a TP53 mutation and a previously unreported C2orf92-EML4 fusion of unknown clinical significance. Based on current clinical evidence for ALK TKIs, lorlatinib has demonstrated superior efficacy in prolonging PFS, even in patients with concurrent TP53 mutations, compared with other ALK-TKIs. To address the patient’s multiple complex genomic alterations, lorlatinib was selected as first-line therapy at a dose of 100 mg orally once daily. A follow-up chest CT one month after treatment initiation showed a significant response in lung lesions and PE, with complete resolution of pleural and pericardial effusions (Figure 4B). The therapeutic efficacy achieved a partial response (PR). Despite sustained regression of the primary lesions on the 9-month post-treatment chest CT, a new small pulmonary nodule was detected (Figure 4C). Given the patient’s favorable primary response to lorlatinib and the impracticality of biopsy for the small nodule, an inflammatory etiology was suspected, and a one-week course of oral levofloxacin was administered. A subsequent chest CT two months later confirmed sustained regression of the primary lesions and complete resolution of the new nodule (Figure 4D). To date, the patient has achieved a PFS of over 24 months with ongoing disease remission. Treatment-related adverse events (AEs) were mild, limited to grade 2 hyperlipidemia, which is well-controlled with lipid-lowering medication.

Figure 1 Chest CT showing a large right-sided pleural effusion and a small pericardial effusion (December 26, 2023). CT, computed tomography.
Figure 2 Cytological and immunohistochemical analysis of pleural effusion. (A) Low-power cytology showing sparse cellular material (H&E, ×40). (B) High-power view revealing clusters of atypical epithelial cells with nuclear pleomorphism (H&E, ×100). (C) Cell block section demonstrating glandular structures with nuclear pleomorphism (H&E, ×400). (D) Focal TTF-1 immunoreactivity in tumor cells, supporting a pulmonary origin (IHC, ×200). H&E, hematoxylin and eosin; IHC, immunohistochemistry; TTF-1, thyroid transcription factor 1.
Figure 3 ALK expression detected by D5F3 immunohistochemistry. Representative images showing strong, diffuse cytoplasmic staining in tumor cells at original magnifications of ×100 (left, scale bar =100 µm), ×200 (middle, scale bar =100 µm), and ×200 (right, scale bar =100 µm). ALK, anaplastic lymphoma kinase.
Figure 4 CT scan of the patient. (A) Multiple pulmonary emboli (red arrow) and lung lesions (red circle) (January 2024). (B) Significant regression of lesions (red circle) and pulmonary emboli (red arrow) (February 2024). (C) Continued regression (red circle) and new pulmonary nodule in the right lung (red circle) (October 2024). (D) Complete resolution of the nodule (red circle) and continued regression (red circle) (December 2024). CT, computed tomography.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In NSCLC, ALK rearrangement is recognized as a well-validated oncogenic driver. The ALK gene encodes a transmembrane tyrosine kinase receptor that plays a critical regulatory role in neural differentiation during embryonic development and is rarely expressed in adult tissues. Oncogenic activation of ALK primarily occurs through three mechanisms: copy number variations arising from gene amplification, point mutations within the kinase domain, and most commonly chromosomal translocation leading to fusion gene formation (8). These genetic alterations in ALK gene result in sustained activation of the ALK protein, with fusion proteins exhibiting constitutive kinase activity that drives tumorigenesis.

While EML4-ALK is the most prevalent ALK fusion variant, our study identified a novel WIPF1-ALK fusion that retains the complete ALK kinase domain, suggesting it possesses comparable oncogenic potential. The WIPF1 gene encodes a protein critical for the dynamic regulation of the actin cytoskeleton, and its aberrant expression is closely associated with the invasive and metastatic capabilities of tumor cells (9). Notably, NGS analysis confirmed the presence of the WIPF1-ALK fusion across multiple specimen types (Figure S1), with mutation variant allele frequencies (VAFs) of 0.51% in plasma, 7.81% in pleural effusion, and 4.57% in tissue samples. In contrast, EML4-ALK was detected exclusively in pleural effusion at a low VAF of 0.64% and was undetectable in both plasma and tissue specimens (Table 1). The pleural effusion sample exhibited the highest WIPF1-ALK VAF (7.81%), supporting its role as a key driver of tumor progression (10). The WIPF1-ALK fusion resulted from the breakage and rearrangement of WIPF1 exon 6 and ALK exon 15 (Figure 5). Of note, both WIPF1 and ALK are located on chromosome 2p, and their fusion likely arose from an intrachromosomal inversion-a rearrangement that mediates efficient, constitutive ALK activation. This molecular event may explain the aggressive clinical features observed in this case, including suspected tumor thrombi and high tumor burden. Although EML4-ALK was also detected, WIPF1-ALK was consistently present across all tested specimens, suggesting it represents the primary driver of the patient’s aggressive disease course. These findings highlight the molecular heterogeneity of non-canonical ALK fusions and their clinical relevance in advanced NSCLC.

Table 1

Somatic genomic alterations and their variant allele frequencies across plasma, pleural effusion, and tumor tissue samples. Abundance refers to variant allele frequency in respective samples.

Gene Variant Mutation type Plasma abundance Pleural effusion abundance Tissue abundance
ALK WIPF1-ALK fusion WIPF1:exon6~ALK:exon15 0.51% 7.81% 4.57%
ALK EML4-ALK fusion EML4:exon6~ALK:exon17 - 0.64% -
TP53 p.R110L, missense mutation in exon 4 c.329G>T (p.R110L) 0.38% 4.72% 3.93%
EML4 C2orf92-EML4 fusion C2orf92:exon1~EML4:exon7 0.06% 2.19% 0.41%

ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein-like 4 gene; WIPF1, WAS/WASL interacting protein family member 1.

Figure 5 Identification of WIPF-ALK and EML4-ALK double-fusion. ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein-like 4 gene; WIPF1, WAS/WASL interacting protein family member 1.

Current evidence indicates that first- and second-generation ALK TKIs exhibit variable efficacy against rare ALK fusion variants. For instance, favorable responses have been documented in patients with uncommon ALK fusions such as STRN-ALK (11), in contrast, first- and second-generation TKIs show limited efficacy against HIP1-ALK fusions (12). These discrepancies highlight the unmet need for fusion-specific therapeutic strategies. Lorlatinib, a third-generation ALK-TKI, possesses potent blood-brain barrier (BBB) penetration and demonstrates broad-spectrum activity against diverse ALK fusion variants (5). As summarized in Table 2, while lorlatinib has shown efficacy across multiple tumor types-including gliomas and sarcomas-accumulating data specifically underscore its clinical utility in NSCLC harboring rare ALK fusions. In lung adenocarcinoma cases involving rare fusion partners (e.g., FAM179A, HIP1, SQSTM1), lorlatinib has achieved PR or stable disease (SD), even when administered as later-line therapy. Furthermore, emerging reports confirm that lorlatinib retains activity in the presence of co-occurring genomic alterations (e.g., TP53, RB1) and central nervous system (CNS) involvement, supporting its role as a viable therapeutic option for patients with rare ALK fusions (Table 2). In our case, the patient harboring dual ALK fusions (WIPF1-ALK and EML4-ALK) and a concurrent TP53 mutation achieved rapidtumor regression and sustained disease control for more than 24 months. This finding confirms the potent clinical activity of lorlatinib against the novel WIPF1-ALK fusion and validates its efficacy in complex molecular profiles characterized by both rare ALK fusions and coexisting TP53 mutations (21,22).

Table 2

Summary of clinical efficacy of lorlatinib in rare ALK fusion variants

Reference Year Tumor type ALK fusion variant Accompanying mutations Lorlatinib treatment Response
Yan et al. (13) 2020 Lung adenocarcinoma FAM179A-ALK (F1,A19) Not reported 2nd line PR (intracranial), SD (lung), PFS >27 months
Li et al. (14) 2023 NSCLC (adenocarcinoma transformed to squamous) ALK-RNF144A HIP1-ALK RB1 loss-of-function 7th line SD >2 months, OS >18 months
Xu et al. (15) 2023 NSCLC transformed to SCLC EML4-ALK (V3 variant) ALK V1180L; TP53; RB1; KRAS G12D; PIK3CA 2nd line PR (pulmonary and intracranial); sustained response at 5 months
Ogimoto et al. (12) 2024 Lung adenocarcinoma HIP1-ALK (H30,A20) BRAF V600E; ALK V1180L 3rd line PFS 5 months
Luo et al. (16) 2025 Lung adenocarcinoma KIF5B-ALK (K15,A20) TP53, ROS1 1st line SD >8 months
Vitale et al. (17) 2025 Lung adenocarcinoma EML4-ALK (E6,A18) Not reported 1st line CR (intracranial), CMR (systemic)
Gu et al. (18) 2025 Lung adenocarcinoma SQSTM1-ALK (S6,A20) Not reported 3rd line PFS 15 months
Zhou et al. (19) 2025 Mucinous lung adenocarcinoma KANK1-ALK TP53 p.D259Y 1st line Primary resistance, rapid progression
Tang et al. (20) 2025 Thoracic IMT EML4-ALK, PLB1-ALK, ALMS1-ALK (triple fusion) Not reported 1st line PR, PFS >15 months

ALK, anaplastic lymphoma kinase; CMR, complete metabolic response; CR, complete response; IMT, inflammatory myofibroblastic tumor; OS, overall survival; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; PFS, progression-free survival; PR, partial response; SD, stable disease.

This study reports a clinically meaningful case of lung adenocarcinoma harboring a rare ALK fusion variant. Through NGS, the patient was identified to carry a dual WIPF1-ALK/EML4-ALK fusion, along with a concurrent TP53 mutation. First-line treatment with lorlatinib, a third-generation ALK TKI, resulted in a rapid and durable clinical response, characterized by significant tumor regression, complete resolution of malignant pleural effusion, and improvement in pulmonary embolism-related manifestations-ultimately leading to marked enhancement of the patient’s quality of life. This case carries several key clinical implications: first, the identification of the novel WIPF1-ALK fusion expands the molecular spectrum of ALK-rearranged NSCLC. Second, it validates the robust efficacy of lorlatinib in treating this rare and complex genomic profile, including dual ALK fusions and coexisting TP53 mutation. Third, it underscores the indispensable role of comprehensive genomic profiling (CGP) in guiding precision oncology practice. Collectively, this case provides novel evidence supporting the clinical utility of ALK-TKIs, suggesting that lorlatinib may serve as an effective therapeutic strategy for NSCLC patients with rare ALK fusion variants. Given the paucity of data on rare ALK fusions, further investigations—including large-scale clinical trials and in-depth mechanistic studies—are warranted to clarify the differential sensitivity of distinct ALK fusion variants to targeted therapies and optimize treatment algorithms for this patient population.

Conclusions

This case demonstrates that lorlatinib can achieve profound and durable efficacy in a patient with metastatic lung adenocarcinoma harboring a rare WIPF1-ALK/EML4-ALK double-fusion and a concomitant TP53 mutation. It underscores the critical role of CGP in identifying such rare and complex oncogenic drivers. These findings reinforce that potent, targeted therapy should be pursued even in the presence of non-canonical fusion variants and resistance-associated co-mutations, thereby expanding the actionable landscape of precision oncology for ALK-positive NSCLC.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0129/rc

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0129/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2026-1-0129/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Zheng D, Wang R, Zhang Y, et al. Prevalence and clinicopathological characteristics of ALK fusion subtypes in lung adenocarcinomas from Chinese populations. J Cancer Res Clin Oncol 2016;142:833-43. [Crossref] [PubMed]
  2. Kauffmann-Guerrero D, Kahnert K, Huber RM. Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer. Drugs 2021;81:87-100. [Crossref] [PubMed]
  3. Mok T, Camidge DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol 2020;31:1056-64. [Crossref] [PubMed]
  4. Ou SI, Solomon BJ, Besse B, et al. Final Overall Survival and Long-Term Safety of Lorlatinib in Patients With ALK-Positive NSCLC From the Pivotal Phase 2 Study: A Brief Report. J Thorac Oncol 2025;20:513-20. [Crossref] [PubMed]
  5. Solomon BJ, Liu G, Felip E, et al. Lorlatinib Versus Crizotinib in Patients With Advanced ALK-Positive Non-Small Cell Lung Cancer: 5-Year Outcomes From the Phase III CROWN Study. J Clin Oncol 2024;42:3400-9. [Crossref] [PubMed]
  6. Ou SI, Zhu VW, Nagasaka M. Catalog of 5' Fusion Partners in ALK-positive NSCLC Circa 2020. JTO Clin Res Rep 2020;1:100015. [Crossref] [PubMed]
  7. Liang Q, Xu H, Liu Y, et al. Coexistence of a novel NBEA-ALK, EML4-ALK double-fusion in a lung adenocarcinoma patient and response to alectinib: A case report. Lung Cancer 2021;162:86-9. [Crossref] [PubMed]
  8. Du X, Shao Y, Qin HF, et al. ALK-rearrangement in non-small-cell lung cancer (NSCLC). Thoracic Cancer 2018;9:423-30.
  9. Pan Y, Lu F, Xiong P, et al. WIPF1 antagonizes the tumor suppressive effect of miR-141/200c and is associated with poor survival in patients with PDAC. J Exp Clin Cancer Res 2018;37:167. [Crossref] [PubMed]
  10. He X, Jiao XD, Liu K, et al. Clinical Responses to Crizotinib, Alectinib, and Lorlatinib in a Metastatic Colorectal Carcinoma Patient With ALK Gene Rearrangement: A Case Report. JCO Precis Oncol 2021;5:PO.20.00534.
  11. Zhang L, Xiao P, Meng F, et al. STRN-ALK Fusion in Lung Adenocarcinoma with Brain Metastasis Responded Well to Ensartinib: A Case Report. Curr Oncol 2022;29:6749-53. [Crossref] [PubMed]
  12. Ogimoto A, Katsurada N, Yatani A, et al. HIP1-ALK-Rearranged Lung Cancer in a Young Adult With BRAF V600E Mutation Detected After ALK Tyrosine Kinase Inhibitor Therapy: A Case Report. JTO Clin Res Rep 2024;5:100612. [Crossref] [PubMed]
  13. Yan J, Zhou X, Pan D. A case of one lung adenocarcinoma patient harboring a novel FAM179A-ALK (F1, A19) rearrangement responding to lorlatinib treatment. Lung Cancer 2020;147:26-9. [Crossref] [PubMed]
  14. Li H, Liu J, Lan S, et al. An advanced NSCLC patient with ALK-RNF144A and HIP1-ALK fusions treated with ALK-TKI combination therapy: a case report. Transl Lung Cancer Res 2023;12:2538-49. [Crossref] [PubMed]
  15. Lingling X, Maoxi C, Wei Y, et al. Transformation of NSCLC to SCLC harboring EML4-ALK fusion with V1180L mutation after alectinib resistance and response to lorlatinib: A case report and literature review. Lung Cancer 2023;186:107415. [Crossref] [PubMed]
  16. Luo Y, Ouyang W. Case Report: A rare case of ALK-KIF5B gene fusion benefited from treatment with lorlatinib. Front Oncol 2025;15:1594072. [Crossref] [PubMed]
  17. Vitale A, De Paolis E, Russo J, et al. Complete Response to Lorlatinib in Lung Adenocarcinoma With EML4-ALK Fusion Variant (E6;A18): Case Report and Literature Review. J Natl Compr Canc Netw 2025;23:e257099. [Crossref] [PubMed]
  18. Gu J, Zhang J, Li S, et al. Case Report: Treatment response of SQSTM1-ALK fusion lung adenocarcinoma to multiple ALK inhibitors. Front Pharmacol 2025;16:1608080. [Crossref] [PubMed]
  19. Zhou L, Huang W, Zhu Y, et al. KANK1-ALK, a rare ALK fusion in mucinous lung adenocarcinoma with primary resistance to ALK-TKI treatment: A case report. Precision Medical Sciences 2025;14:156-9.
  20. Tang LB, Peng YL, Yang XR, et al. Partial response to lorlatinib in thoracic inflammatory myofibroblastic tumor harboring complex and rare ALK fusions: a case report. Transl Lung Cancer Res 2025;14:631-8. [Crossref] [PubMed]
  21. Mudumba R, Liu X, Davis I, et al. Real-world costs, treatment patterns, and clinical outcomes associated with treatments for advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. J Manag Care Spec Pharm 2025;31:890-9. [Crossref] [PubMed]
  22. Bearz A, Martini JF, Jassem J, et al. Efficacy of Lorlatinib in Treatment-Naive Patients With ALK-Positive Advanced NSCLC in Relation to EML4::ALK Variant Type and ALK With or Without TP53 Mutations. J Thorac Oncol 2023;18:1581-93. [Crossref] [PubMed]
Cite this article as: Wang S, Chen X, Ma Y, Xia Q, Yuan D, Lv T, Yao Y. Case report: first-line lorlatinib in metastatic lung adenocarcinoma with a novel WIPF1-ALK and EML4-ALK dual fusion. Transl Lung Cancer Res 2026;15(5):156. doi: 10.21037/tlcr-2026-1-0129

Article Options

Download Citation

Share