Pemetrexed

(Alimta®)

Pemetrexed

Drug updated on 5/17/2024

Dosage FormInjection (intravenous; 100 mg, 500 mg)
Drug ClassFolate analog metabolic inhibitors
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated in combination with pembrolizumab and platinum chemotherapy, for the initial treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.
  • Indicated in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic, non-squamous NSCLC.
  • Indicated as a single agent for the maintenance treatment of patients with locally advanced or metastatic, non-squamous NSCLC whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
  • Indicated as a single agent for the treatment of patients with recurrent, metastatic non-squamous, NSCLC after prior chemotherapy.

Summary
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  • Pemetrexed (Alimta) is indicated for the treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC), both as a single agent and in combination with other drugs such as pembrolizumab, platinum chemotherapy, or cisplatin. It is also used for maintenance treatment after initial chemotherapy.
  • The studies sourced information from systematic reviews and meta-analyses focusing on pemetrexed's use in various combinations for NSCLC.
  • In ALK-mutated NSCLC, pemetrexed-based chemotherapy shows less efficacy compared to targeted therapies like lorlatinib in terms of progression-free survival. Nevertheless, it remains an effective first-line treatment option.
  • When combined with carboplatin, pemetrexed demonstrated superior outcomes in overall survival and progression-free survival compared to EGFR-TKI therapy alone, indicating significant benefits over TKI monotherapy, especially for patients with EGFR mutations.
  • Data for Asian populations and specific EGFR mutation subsets did not significantly favor pemetrexed-based chemotherapy over other treatments like EGFR tyrosine kinase inhibitors (TKIs) in overall survival benefits but demonstrated effectiveness regarding progression-free survival (PFS).
  • Maintenance therapy combining bevacizumab and pemetrexed resulted in significant improvement in both PFS and OS compared to monotherapy using either drug individually, despite increased adverse events associated with this combination therapy, making it a preferable choice among eligible patients.
  • A notable improvement was observed when combining pembrolizumab, pemetrexed, and platinum chemotherapy, showing a superior benefit-risk profile during the maintenance phase of treatment, outperforming historical data on pemetrexed maintenance while maintaining comparable safety profiles, thus establishing itself as a strong first-line treatment option.
  • Patient subgroups, such as those having ALK or EGFR mutations or certain genetic aberrations, may experience different benefits from pemetrexed-based therapies. For instance, targeted therapies may offer more significant benefits in the presence of certain mutations. Combination therapies involving pemetrexed tend to provide improved PFS and OS but might increase toxicity.

Product Monograph / Prescribing Information

Document TitleYearSource
Alimita (pemetrexed) Prescribing Information.2022Lilly USA LLC, Indianapolis, IN

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy and safety of first-line treatments for patients with advanced anaplastic lymphoma kinase mutated, non-small cell cancer: a systematic review and network meta-analysis.2023Cancer
Overall survival and safety with pemetrexed/platinum ± Anti-VEGF followed by pemetrexed ± Anti-VEGF maintenance in advanced nonsquamous non-small-cell lung cancer: a pooled analysis of 4 randomized studies.2022Clinical Lung Cancer
Efficacy and safety of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor combination therapy as first-line treatment for patients with advanced EGFR-mutated, non-small cell lung cancer: a systematic review and Bayesian network meta-analysis.2022Cancers
Overall survival benefits of first-line treatments for Asian patients with advanced epidermal growth factor receptor-mutated NSCLC harboring exon 19 deletion: a systematic review and network meta-analysis.2022Cancers
Overall survival benefits of first-line treatments for asian patients with advanced EGFR-mutated NSCLC harboring L858R mutation: a systematic review and network meta-analysis.2022JTO Clinical and Research Reports.
Concurrent chemoradiotherapy with cisplatin + S-1 versus cisplatin + other third-generation agents for locally advanced non-small-cell lung cancer: a meta-analysis of individual participant data.2022BioMed Central Pulmonary Medicine
The efficacy and toxicity of maintenance therapy with bevacizumab plus pemetrexed versus bevacizumab/pemetrexed alone for stage IIIB/IV nonsquamous non-small cell lung cancer: a meta-analysis of randomized controlled trials.2021Journal of Clinical Pharmacy and Therapeutics
Systematic review and meta-analysis of the predictive power of MTHFR polymorphisms for pemetrexed drug efficacy and toxicity in non-small cell lung cancer patients.2021Journal of Chemotherapy
First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non-squamous non-small cell lung cancer.2021The Cochrane Database of Systematic Reviews.
Pemetrexed maintenance with or without pembrolizumab in non-squamous non-small cell lung cancer: a cross-trial comparison of keynote-189 versus paramount, pronounce, and JVBL.2021 Lung cancer
Clinical option of pemetrexed-based versus paclitaxel-based first-line chemotherapeutic regimens in combination with bevacizumab for advanced non-squamous non-small-cell lung cancer and optimal maintenance therapy: evidence from a meta-analysis of randomized control trials.2021BioMed Central Cancer
Efficacy and safety of first line treatments for patients with advanced epidermal growth factor receptor mutated, non-small cell lung cancer: systematic review and network meta-analysis.2019British Medical Journal

Clinical Practice Guidelines