Efficacy of Pemetrexed-Based Chemotherapy in Patients with ROS1 Fusion-Positive Lung Adenocarcinoma Compared with in Patients Harboring Other Driver Mutations in East Asian Populations.
The efficacy of pemetrexed-based chemotherapy in patients with advanced lung adenocarcinoma with novel ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1) oncogenic rearrangement is unclear. This study aimed to compare the efficacy of pemetrexed-based chemotherapy in patients with advanced ROS1-fusion lung adenocarcinoma with its efficacy in those having different driver mutations.



We retrospectively identified patients with advanced lung adenocarcinoma who were screened for epidermal growth factor receptor gene (EGFR) mutations, echinoderm microtubule associated protein like 4 gene (EML4)-anaplastic lymphoma receptor tyrosine kinase gene (ALK) translocation, Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutations, and ROS1 fusion by using multiplex reverse-transcriptase polymerase chain reaction. Patients who received pemetrexed-based therapy were enrolled for further analysis. The demographic data, clinical outcomes, and thymidylate synthase immunostaining (H-score) of patients with ROS1 fusion-positive lung adenocarcinomas were compared with those of patients harboring EGFR mutations, EML4-ALK fusion, KRAS mutations, and quadruple negativity.



A total of 253 patients with advanced lung adenocarcinoma received a pemetrexed-based regimen and were classified on the basis of molecular findings as follows: 102 patients (40.3%) with EGFR mutations, 32 patients (12.6%) with EML4-ALK translocation, three patients (1.2%) with KRAS mutations, 19 patients (7.5%) with ROS1 fusion, and 97 patients (38.3%) with quadruple-negative status. Patients with ROS1 fusion had a better overall response rate (57.9%, p = 0.026), disease control rate (89.5%, p = 0.033), and longer progression-free survival (7.5 months, p = 0.003) compared with patients harboring other driver mutations. However, the H-score of thymidylate synthase was not associated with the response to pemetrexed therapy in patients with different molecular subtypes of lung adenocarcinoma.



ROS1 fusion positivity is probably a favorable factor of pemetrexed-based therapy for patients with lung adenocarcinoma.
Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Republic of China; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Republic of China.
Yen-Fu
YF
Chen
Department of Pathology, National Taiwan University Hospital, Taipei, Republic of China; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Min-Shu
MS
Hsieh
Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin, Republic of China; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Republic of China.
Shang-Gin
SG
Wu
Department of Pathology, National Taiwan University Hospital, Taipei, Republic of China; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Yih-Leong
YL
Chang
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Republic of China; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Republic of China.
Chong-Jen
CJ
Yu
Department of Oncology, National Taiwan University Hospital, Taipei, Republic of China; Graduate Institute of Oncology Cancer Research Centre, National Taiwan University, Taipei, Republic of China.
James Chih-Hsin
JC
Yang
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Republic of China; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Republic of China.
Pan-Chyr
PC
Yang
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei 10002, Republic of China; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Republic of China. Electronic address: jyshih@ntu.edu.tw.
Jin-Yuan
JY
Shih
D000230:Adenocarcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D000068437:Pemetrexed / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012189:Retrospective Studies; D013940:Thymidylate Synthase / Q000032:analysis
D000970:Antineoplastic Agents; C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; C000715470:MAS1 protein, human; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D000068437:Pemetrexed; D013940:Thymidylate Synthase; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D016283:Proto-Oncogene Proteins p21(ras)
EGFR mutation; EML4-ALK fusion; KRAS mutation; ROS1 fusion; pemetrexed-based therapy