Abstract
Simple SummaryThe chemotherapy agent pemetrexed is currently considered in combination with other therapies for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) in patients negative for gene mutations/rearrangements. The aim of this review was to highlight data from clinical studies with pemetrexed in patients with advanced nonsquamous NSCLC positive for gene mutations/rearrangements. The results of the review suggest that pemetrexed could be a treatment option in patients with advanced nonsquamous NSCLC positive for certain gene mutations/rearrangements.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.
Highlights
Non-small-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases [1] and is the leading cause of death from cancer worldwide [2]
Patients with ROS proto-oncogene1 (ROS1) rearrangement may benefit from pemetrexed-based treatment, with progression-free survival (PFS) similar to that in anaplastic lymphoma kinase (ALK)-positive patients and longer than that in patients with echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK), epidermal growth factor receptor (EGFR) or Kirsten rat sarcoma (KRAS) mutations, or wild-type disease (Supplementary Table S5)
Guidelines generally recommend pemetrexed for first- and later-line treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) in patients negative for gene mutations/rearrangements, this nonsystematic literature review suggests that survival outcomes with pemetrexed in patients with gene mutations/rearrangements are comparable to those in unselected patients
Summary
Non-small-cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases [1] and is the leading cause of death from cancer worldwide [2]. Guidelines generally recommend pemetrexed in combination with carboplatin or cisplatin and immunotherapy for first-line treatment and as monotherapy for later-line treatment of advanced nonsquamous NSCLC in patients with a performance status of 0/1 who are negative for gene mutations/rearrangements (i.e., with wild-type disease; Supplementary Table S2) [3,4,56,57]. Since 2018, the European Society of Medical Oncology (ESMO) has recommended pemetrexed plus carboplatin and gefitinib as first-line treatments in patients with an EGFR-activating mutation [4,56] The aim of this narrative review is to highlight the role of pemetrexed in the treatment of targetable nonsquamous advanced NSCLC by reviewing clinical outcomes with the drug in published clinical studies, including systematic reviews, randomized controlled trials, prospective cohort studies, post-hoc analyses, and retrospective chart reviews.
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