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Senthil Kumar: Comprehensive Overview of First-Line Treatment for Metastatic Esophageal Cancer

cinj.org

Jan 11, 2025, 21:15

Senthil Kumar: Comprehensive Overview of First-Line Treatment for Metastatic Esophageal Cancer

Senthil Kumar, Medical Oncologist at Red Hills Chennai, shared a post on X:

“Comprehensive Overview of First-Line Treatment for Metastatic Esophageal / OGJ Cancer.

Key Clinical Trials and Outcomes

KEYNOTE-590 Trial

Population: Advanced Esophageal SCC and adenocarcinoma.

Median OS: 12.4 vs. 9.8 months (Pembrolizumab + Cisplatin/5-FU vs. Chemo alone).
Median PFS: 6.3 vs. 5.6 months.

Additional Benefits:

Significant survival advantage in SCC.
Strong outcomes in PD-L1 CPS ≥10 populations.

CheckMate 648 Trial

Population: Esophageal SCC (irrespective of PD-L1 status).

Median OS:

Chemo: 10.7 months.
Nivolumab + Chemo (Fluoropyrimidine + Platinum): 13.2 months (overall) and 15.4 months (PD-L1 ≥1%).
Nivolumab + Ipilimumab: 12.8 months (overall) and 13.7 months (PD-L1 ≥1%).

Median PFS:

Nivolumab + Chemo: 7.4 months.
Chemo alone: 5.6 months.

Note: Benefits primarily observed in TPS ≥1 populations.

ESCORT-1st Trial

Population: Esophageal SCC (predominantly Chinese cohort).

Median OS: 15.3 vs. 12.0 months (Camrelizumab + Chemo vs. Chemo alone).
Median PFS: 6.9 vs. 5.6 months.

CheckMate 649 Trial

Population: CPS >5 (Esophageal and GEJ cancers).

Median OS: 14.4 vs. 11.1 months (Nivolumab + Chemo [Fluoropyrimidine + Platinum] vs. Chemo alone).
Median PFS: 8.3 vs. 6.1 months.

KEYNOTE-859 Trial

Population: Advanced esophageal cancer.

Median OS: 12.9 vs. 11.5 months (Pembrolizumab + Chemo [Cisplatin/5-FU] vs. Chemo alone).

ATTRACTION-4 Trial

Population: HER2-negative gastric and GEJ cancers.

Median PFS: 9.5 vs. 6.9 months.
Median OS: 17 vs. 17 months (Nivolumab + Chemo vs. Chemo alone; numerically high OS, but not statistically significant).

HER2-Positive Adenocarcinomas

Key Data:

TOGA Trial: OS 14 vs. 11 months.
KEYNOTE-811 (PD-L1 ≥1): OS 20 vs. 16 months with Trastuzumab + Pembrolizumab + Chemo.

Final Insights

Best Regimens for Advanced Esophageal Cancer:

HER2+ Adenocarcinoma:

CPS ≥1: Quadruplet (Trastuzumab + Pembrolizumab + Platinum Doublet).
CPS <1: Trastuzumab + Chemo Doublet.

HER2-Negative, MSI-High:

Pembrolizumab/Nivolumab + Chemo Doublet.

HER2-Negative, MMR Proficient:

CPS <5: Chemo.
CPS ≥5: Nivolumab + Chemo.
CPS ≥10: Pembrolizumab + Chemo.

Squamous Cell Carcinoma:

Chemo + Pembrolizumab/Nivolumab for TPS ≥1 or CPS ≥5.

Chemo Backbone:

Doublets: Standard for efficacy and tolerability.
Triplets (DCF, ECF): Higher toxicity with no added survival benefit, generally avoided.”

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Senthil Kumar: Comprehensive Overview of First-Line Treatment for Metastatic Esophageal Cancer