{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T14:43:38Z","timestamp":1778942618238,"version":"3.51.4"},"reference-count":68,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013platinum 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.<\/jats:p>","DOI":"10.3390\/cancers12092658","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T07:27:33Z","timestamp":1600414053000},"page":"2658","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2854-5067","authenticated-orcid":false,"given":"Jin-Yuan","family":"Shih","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, National Taiwan University Hospital, No. 7 Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, National Taiwan University, 7 Chung-Shan S. Rd., Taipei 100, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Palliative Medicine, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Cheng","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Songshan District, Fuxing North Road 365, Taipei 105, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocio","family":"Varea","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company, Songshan District, Fuxing North Road 365, Taipei 105, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-We","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Oncology, Asan Medical Center, 88 Olympic-Ro 43-Gil, Songpa-Gu, Seoul 05505, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"ref_1","unstructured":"Noone, A.M., Howlader, N., Krapcho, M., Miller, D., Brest, A., Yu, M., Ruhl, J., Tatalovich, Z., Mariotto, A., and Lewis, D.R. 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