Abstract 6495: Lenvatinib as a potential treatment option for invasive mucinous lung adenocarcinoma
Authors: Demir Tarik , Moloney Carolyn , Chung Liam Il-Young , Chae Young Kwang 
Published: March 2024

Abstract
Introduction: Invasive mucinous adenocarcinoma (IMA) accounts for approximately 4-20% of non-small-cell lung carcinoma (NSCLC). Genetic alterations and RNA sequencing analysis of IMAs reveal a unique mucinous signature similar to gastrointestinal mucinous tumors. Due to its rarity, focused clinical trials for IMA patients are often not feasible. These patients respond poorly to platinum-based conventional chemotherapy, or immunotherapy. Lenvatinib is a multitargeted-TKI with demonstrated activity in patients with RET fusion-positive lung adenocarcinoma, thyroid, hepatocellular and gastric carcinoma.
Methods: Here, we present two RET fusion-negative mucinous lung adenocarcinoma cases that received a multitargeted TKI lenvatinib with a clinical and survival benefit.
Results: Case #1: An 81-year-old female initially diagnosed with cT4N0M0 IMA (TTF1 and CDX2 focally positive) was started on neoadjuvant treatment for a 12cm tumor. She underwent right thoracotomy/right lower lobectomy/mediastinal lymph node dissection, and pathology confirmed ypT4N1M0 mucinous adenocarcinoma. Three months post-operatively, the patient had disease progression in the lungs. She had no targetable mutations. She had four subsequent lines of treatment including nivolumab/nab-paclitaxel as the fourth-line treatment. After six months of nivolumab/nab-paclitaxel, lenvatinib was added to the combination due to clear disease progression evident on imaging. After twelve cycles of nivolumab/nab-paclitaxel/lenvatinib combination treatment, patient achieved a partial response per RECIST 1.1 (-35.7% change from baseline to current). The patient reported less dyspnea and increased activity tolerance. Approximately nine months after the start of the treatment, patient showed progressive lung disease. The patient died after one more line treatment with 41 months of total overall survival. Case#2: A 56-year-old male initially diagnosed with stage IVA IMA (TTF1 negative). After four lines of treatments, patient was started on lenvatinib alone. The patient reported marked improvement in dyspnea and pain and increased activity tolerance with lenvatinib. Imaging confirmed treatment response after three months of treatment. The patient was subsequently enrolled in the double lung transplant (DLT) registry aimed for lung-limited malignancies (D.R.E.A.M.) registry study (NCT05671887), and he is alive with 25 months follow-up since DLT.
Conclusion: We report two cases of metastatic RET fusion-negative mucinous lung adenocarcinoma, in which treatment with the multitargeted TKI Lenvatinib led to significant clinical improvement. Biological rationale to explain the effect of lenvatinib in invasive mucinous lung adenocarcinoma needs to be explored.
Citation Format: Tarik Demir, Carolyn Moloney, Liam Il-Young Chung, Young Kwang Chae. Lenvatinib as a potential treatment option for invasive mucinous lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6495.