Use of Pralsetinib as Neoadjuvant Therapy for Non-Small Cell Lung Cancer Patient With RET Rearrangement

Abstract

RET rearrangements are rare, and occur in 1%-2% of all non-small cell lung cancer (NSCLC) patients. Pralsetinib has a significant anti-tumor effect in patients with advanced NSCLC and a RET rearrangement. Previous studies have confirmed the efficiency of neoadjuvant target therapy for NSCLC. Herein we present a case involving a female patient who was diagnosed with stage IIIA lung adenocarcinoma and harbored a KIF5B-RET rearrangement based on next-generation sequencing. Radiologic downstaging was indicated after pralsetinib treatment. Therefore, a right lower lobectomy and systemic lymphadenectomy were successfully performed. The postoperative pathologic results revealed a response rate of 74% for primary tumor and no residual viable tumor cells were observed in lymph nodes. The tumor, nodes, and metastases (TNM) stage was ypT1cN1M0. The tumor micro-environment (TME) of the primary tumor was also assessed.

Neoadjuvant Savolitinib targeted therapy stage IIIA-N2 primary lung adenocarcinoma harboring MET Exon 14 skipping mutation: A case report

“…Previous clinical trials have already verified the availability of EGFR and ALK inhibitors neoadjuvant targeted therapy in the disease control and pathological downstaging for early-stage NSCLC patients harboring the corresponding mutation, and some case reports also observed that target therapy provided effective radiologic and pathologic response in ALK , RET and ROS1 -positive resectable NSCLC patients ( 3 , 6 , 13 – 15 ). MET ex14m is an independent oncogenic driver occurring in 2.8% of resected stage I-III NSCLC patients ( 16 ).…”

“…Immunohistochemistry outcomes were presented as: HE (A), TTF-1 (+) (B), NapsinA (+) (C), CK7 (+) (D), CK5/6 (-), CK (pan) (+), and Ki-67 (+, about 50%). some case reports also observed that target therapy provided effective radiologic and pathologic response in ALK, RET and ROS1-positive resectable NSCLC patients (3,6,(13)(14)(15). METex14m is an independent oncogenic driver occurring in 2.8% of resected stage I-III NSCLC patients (16).…”

“…Savolitinib is an oral, potent and highly selective type Ib MET inhibitor that has yielded promising activity and acceptable safety profile in patients with pulmonary sarcomatoid carcinoma and other NSCLCs harboring METex14m (2). Recently, a growing body of research has shown the feasibility of the neoadjuvant targeted therapy for early-stage resectable NSCLC patients with anaplastic lymphoma kinase (ALK) fusion gene, epidermal growth factor receptor (EGFR) mutations, RET rearrangements and ROS proto-oncogene 1 (ROS1) rearrangements (3)(4)(5)(6). The fact suggests that the untargeted patients with METex14m had a shorter disease-free survival (DFS) (7).…”

Case report: Recurrent lung infections following treatment with pralsetinib for an elderly patient with RET-fusion positive NSCLC

“…Satisfactory effects have been shown in this study, with partial response in eight patients and disease stabilization in another two patients ( 8 ). In addition, pralsetinib was used as neoadjuvant therapy in a case study, in which a 54-year-old female with stage IIIA lung adenocarcinoma achieved apparent radiologic downstaging after pralsetinib therapy for one month, and the mass of primary tumor was reduced by 74% postoperatively ( 9 ). Even though pralsetinib has consistently shown therapeutic benefits in previous studies, its effects on elderly NSCLC patients with RET fusion remain unclear.…”

Neo-Adjuvant Therapies in Lung Cancer – Past Present and Future Directions

“…Another mutation that is being explored is a RET mutation in NSCLC patients that have been treated with pralsetinib. Zhou et al [36] reported a patient with resectable Stage IIIA NSCLC with a RET mutation (KIF5B-RET fusion). The patient was treated with neoadjuvant pralsetinib for 4 weeks, showing a 74% response rate post-operatively.…”