Prominent response to savolitinib monotherapy in high-grade fetal adenocarcinoma with MET amplification and concurrent brain metastasis: a case report

Abstract

Background: Mesenchymal-epithelial transition (MET) represents a potential therapeutic target in various cancers, with amplification of the MET gene identified in a subset of patients with pulmonary adenocarcinomas. However, MET gene amplification is rarely observed in high-grade fetal adenocarcinoma (H-FLAC).

Case description: Here we present a novel case of a patient diagnosed with stage IV H-FLAC harboring MET amplifications and treated with savolitinib. The 69-year-old male patient, who presented with a primary complaint of cough and white sputum, had a history of hypertension for over 10 years and a 45-year smoking history. The patient received savolitinib monotherapy treatment due to brain metastases. Despite the omission of radiotherapy for asymptomatic brain metastases, a notable response to savolitinib therapy was observed, with a partial response (PR) achieved after 4 weeks and a reduction in the brain tumor. At the time of the submission of this report, the patient received over 24 weeks of savolitinib treatment, and was maintained PR. The patient was still undergoing treatment. This highlights the potential clinical benefits of targeted therapy against MET amplification in H-FLAC.

Conclusions: H-FLAC harboring MET amplification and brain metastasis is rare. Treatment with savolitinib monotherapy resulted in a PR, providing preliminary insights to the efficacy of savolitinib for H-FLAC with MET amplification.

Keywords: Case report; high-grade fetal adenocarcinoma (H-FLAC); mesenchymal-epithelial transition (MET); savolitinib.

Figure 1

The treatment history and pathological diagnosis of the patients. (A) The timeline of treatment. (B) Pathological examination of the biopsy at diagnosis. Hematoxylin-eosin staining (×40) showed glandular and tubular structures in myxoid stroma that was lined with columnar cells. IHC testing (×40) showed positive expression of membrane β-catenin, SALL4, and Ki-67. (C) Hematoxylin-eosin staining (×40) showed complex papillotubular structures composing of pseudostratified columnar cells and morule formation. IHC testing (×40) showed positive expression of P53 and Glypican-3. (D) FISH (×400) validated MET amplification. H-FLAC, high-grade fetal adenocarcinoma; PR, partial response; PD, progressive disease; SD, stable disease; H&E, hematoxylin and eosin; IHC, immunohistochemical; MET, mesenchymal-epithelial transition; FISH, fluorescence in situ hybridization.

Figure 2

Response evaluation by chest CT scan and brain MRI. The tumor assessment was performed according to the RECIST version 1.1. The red arrow indicates the location of the lesion. (A) Chest CT scan of lung lesions and brain MRI before savolitinib treatment. (B) Chest CT scan of lung lesions and brain MRI after 4 weeks of savolitinib treatment revealed a partial response. (C) Chest CT scan of lung lesions and brain MRI after 24 weeks of savolitinib treatment revealed a partial response. CT, computed tomography; MRI, magnetic resonance imaging.