Does pemetrexed work in targetable, nonsquamous non-small-cell lung cancer? A narrative review

Jin Yuan Shih, Akira Inoue, Rebecca Cheng, Rocio Varea, Sang We Kim

Research output: Contribution to journalReview articlepeer-review

11 Citations (Scopus)


Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First-and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK-and ROS1-positive patients and longer than that in patients with Kirsten rat sarcoma (KRAS) virus proto-oncogene mutations or WTD, although the available studies were limited. For Erb-b2 receptor tyrosine kinase 2 (ERRB2) mutations, first-line pemetrexed showed outcomes similar to those for EGFR and KRAS alterations. Data on pemetrexed in patients with KRAS mutations or MNNG HOS-transforming (MET) expression were limited. Pemetrexed could be an option for first-and second-line treatment for TKI failure in nonsquamous advanced NSCLC with select targetable driver mutations.

Original languageEnglish
Article number2658
Pages (from-to)1-18
Number of pages18
Issue number9
Publication statusPublished - 2020 Sept


  • Chemotherapy
  • Gain of function mutation
  • Non-small-cell lung cancer
  • Pemetrexed
  • Progression-free survival


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