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.