Summary

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• This summary is based on the review of 14 systematic review(s)/meta-analysis(es). ^[1-14]
• In advanced NSCLC, the addition of pemetrexed to bevacizumab significantly improved overall survival (OS) (HR (hazard ratio) = 0.87; 95% CI (confidence interval) = 0.76 to 0.99; P = 0.03) and progression-free survival (PFS) (HR = 0.63; 95% CI = 0.55 to 0.72; P < 0.00001), while the combination of gefitinib with pemetrexed-based chemotherapy in EGFR (Epidermal Growth Factor Receptor)-mutated patients further enhanced OS (HR = 0.57, 95% CI 0.37-0.89, P = 0.0125) and PFS (HR = 0.52, 95% CI 0.39-0.70, P < 0.0001).
• Among ALK-positive NSCLC patients, lorlatinib demonstrated superior OS and PFS when compared to pemetrexed-based chemotherapy, particularly showing the best PFS in patients with brain metastases. Alectinib and ensartinib were noted as effective alternatives, with ensartinib providing optimal PFS specifically in Asian populations.
• In maintenance therapy for NSCLC, no OS difference was observed between pemetrexed monotherapy and the combination of pemetrexed with anti-VEGF agents, although PFS was significantly better with the combination (HR = 0.71, 95% CI = 0.65-0.77, P < .00001).
• Comparisons between pemetrexed and gefitinib in previously treated advanced or metastatic NSCLC patients indicated no significant differences in OS (OR (odds ratio) = 0.97, 95% CI = 0.77-1.21, P = .76) or PFS (OR = 1.17, 95% CI = 0.60-2.30, P = .65), indicating similar effectiveness in these endpoints.
• The addition of pemetrexed to bevacizumab in NSCLC patients was associated with a significant increase in grade ≥ 3 adverse events (OR = 2.15; 95% CI = 1.62 to 2.84; P < 0.00001), with higher incidences of anemia, fatigue, thrombocytopenia, and anorexia reported.
• Gefitinib plus pemetrexed-based chemotherapy presented similar rates of adverse events, treatment discontinuation, and disease control compared to other treatment options, indicating a comparable safety profile in advanced NSCLC.
• Lorlatinib showed a poorer safety profile than other first-line treatments for ALK-positive NSCLC, with alectinib demonstrating the most favorable safety outcomes among these options.
• Patients with EGFR exon 19 deletion and exon 21 L858R mutations experience significant PFS improvements when treated with gefitinib plus pemetrexed-based chemotherapy; in ALK-positive NSCLC, lorlatinib offers the best PFS in patients with baseline brain metastases, while among Asian ALK-positive patients, ensartinib shows superior PFS outcomes.