LEAP‑015 Trial Summary
Title: Pembrolizumab + Lenvatinib + Chemotherapy in Advanced Esophageal and GEJ Cancer
Design: Global, randomized, Phase III trial
Population: 765 patients with previously untreated HER2-negative, advanced/metastatic esophageal squamous cell carcinoma (ESCC) or gastroesophageal junction (GEJ) adenocarcinoma
Arms:
Triplet arm: Pembrolizumab + Lenvatinib + 5-FU/cisplatin Control arm: 5-FU/cisplatin chemotherapy alone
Key Efficacy Results
Progression-Free Survival (PFS): Median PFS: 8.2 months (triplet) vs 6.3 months (chemo alone) HR = 0.77 (P = 0.002), favoring the triplet Objective Response Rate (ORR): 57.8% in triplet arm vs 39.8% in control Overall Survival (OS): Data immature at interim analysis Preliminary trends favor the triplet Disease Control Rate (DCR): 91.1% (triplet) vs 83.4% (chemo)
Safety & Toxicity
Any adverse event (AE): 98% in triplet arm vs 92% in chemo arm Grade ≥3 AEs: 65% (triplet) vs 49% (chemo) Grade 5 (fatal) AEs: 5% (triplet) vs <1% (chemo)
Conclusion
Adding pembrolizumab + lenvatinib to chemotherapy improved response rates and PFS, suggesting a more active regimen in HER2‑negative advanced ESCC/GEJ cancer. However, this came with a higher risk of severe and fatal toxicity. Careful patient selection and toxicity management are critical if this regimen moves toward clinical use.