Lenvatinib Pembrolizumab Chemotherapy: ESCC Outcomes Fail to Improve

October 17, 2025 Victoria Sterling -Business Editor Business

Summary of the ⁢LEAP-014 Trial⁤ data:

Here’s a⁢ breakdown of the key findings from the provided text, focusing on efficacy and safety:

Efficacy:

*⁢ Progression-Free ⁤survival (PFS): In patients with a PD-L1 CPS of at least 10, lenvatinib + chemoimmunotherapy showed a trend towards improved PFS (8.1 months) compared ⁢too chemoimmunotherapy alone (6.9 months), but this difference was not statistically notable (HR 0.85, 95% CI 0.69-1.04).
* PFS Rates: At 12 and 24 months, the lenvatinib arm​ had slightly higher PFS rates (36% & 16%)⁣ compared to⁤ the ‌control arm (25% & ⁣14%).
* Objective Response Rate (ORR): Lenvatinib ⁣showed a numerically⁤ higher ORR (62.2%)‌ compared to chemoimmunotherapy alone (54.8%), ⁤with⁢ a delta of 7.3%⁣ (95% CI 0.7%-13.8%). This difference was also not statistically significant.
* Duration of‍ Response (DOR): Median DOR was similar between the two arms (8.1 months for lenvatinib vs. 6.8 months for control). ⁣ A ‍slightly lower percentage of patients in the lenvatinib arm had a response lasting 24 months or greater (17%) ⁤compared to the control arm⁣ (21%).
* ‍ Overall Survival (OS): Crucially, the trial did ‌ not demonstrate an enhancement in overall survival with the addition ⁢of lenvatinib. ‌ This was the primary endpoint⁤ and failure to meet it meant the other positive trends weren’t statistically tested.

Safety:

* High Toxicity: The lenvatinib arm experienced considerably ​ more high-grade⁢ (≥3) adverse events‍ (81.2%) compared to the control arm​ (79.1%).
* Discontinuation Rates: More patients in ​the lenvatinib arm discontinued treatment due to adverse events (33.3%) compared to the control arm (39.0%).
* Treatment-Related Adverse Events (TRAEs): TRAEs were very common in both arms (97.1%‍ in lenvatinib vs. 96.5% in control).
* Common Adverse Events: Common aes (occurring in at least 15% of patients in either arm) ‍included decreased neutrophil count, nausea, hypertension, diarrhea, decreased platelet count, anemia, hypothyroidism, stomatitis, decreased white blood cell count, fatigue, decreased appetite, palmar plantar erythrodysesthesia syndrome, proteinuria, and aspartate aminotransferase increase.
* mortality: 9.7% of patients ​in the⁤ lenvatinib arm experienced grade 5 ⁢(death) adverse events, compared to 11.5% in​ the ​control arm.

In essence, while lenvatinib showed some numerical improvements in PFS and ORR, these were not⁤ statistically significant, and came at the cost of ‍significantly increased toxicity. The​ trial failed to demonstrate an improvement ​in overall survival.