Association Between RET Fusions and Efficacy of Pemetrexed-based Chemotherapy for Patients With Advanced NSCLC in China: A Multicenter Retrospective Study

Clin Lung Cancer. 2020 Sep;21(5):e349-e354. doi: 10.1016/j.cllc.2020.02.006. Epub 2020 Feb 10.

Abstract

Background: Rearranged during transfection (RET) proto-oncogene gene fusions are rare in non-small-cell lung cancer (NSCLC). We compared the efficacy of pemetrexed-based chemotherapy with other chemotherapy regimens in patients with NSCLC with different RET fusion subtypes.

Patients and methods: A retrospective, multicenter study of patients with pathologically confirmed stage IIIB/IV lung adenocarcinomas was conducted. RET rearrangements were detected using next generation sequencing. We analyzed the clinical characteristics of patients with RET-rearranged NSCLC and the efficacy of chemotherapy regimens. We also evaluated the efficacy between groups of patients with and without KIF5B-RET-rearranged lung cancer.

Results: We evaluated 62 patients with NSCLC and RET rearrangements, including 41 with KIF5B-RET, 15 with CCDC6-RET, and 6 with other rare fusion subtypes. Of these 62 patients, 50 had stage IIIB/IV. We also evaluated 40 patients with first-line chemotherapy information available. The median progression-free survival was significantly different between those receiving pemetrexed-based chemotherapy and those receiving other chemotherapy regimens (9.2 vs. 5.2 months; P = .007). The median progression-free survival for patients with KIF5B-RET fusion and non-KIF5B-RET fusion was not significantly different statistically (7.8 vs. 11.2 months; P = .847). For second-line chemotherapy, a statistically significant difference was found between the chemotherapy regimens (4.9 vs. 2.8 months; P = .049). Survival follow-up data were available for 38 patients with advanced NSCLC. The median overall survival was 26.4 months. The overall survival of the patients with RET-rearranged NSCLC who had received pemetrexed-based chemotherapy versus no pemetrexed-based chemotherapy was 35.2 versus 22.6 months (P = .052). No difference in survival was observed between the patients with KIF5B-RET and non-KIF5B-RET rearrangements.

Conclusions: Pemetrexed-based treatment should be considered first when selecting the chemotherapy regimen for patients with NSCLC and RET rearrangements.

Keywords: Chemotherapy regimens; Non–small-cell lung cancer; RET rearrangement; Survival; Treatment.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / drug therapy
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology*
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • Oncogene Proteins, Fusion / genetics*
  • Paclitaxel / administration & dosage
  • Pemetrexed / administration & dosage
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Retrospective Studies
  • Survival Rate

Substances

  • MAS1 protein, human
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Mas
  • Pemetrexed
  • Deoxycytidine
  • Carboplatin
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Paclitaxel
  • Gemcitabine