Excellent Response to Nivolumab and Ipilimumab in Metastatic Gastroesophageal Junction Squamous Carcinoma

Area of Science:

• Oncology
• Immunotherapy
• Gastrointestinal Cancers

Background:

• Unresectable gastroesophageal junction (GEJ) cancers present a significant clinical challenge with limited therapeutic avenues.
• Siewert class III GEJ squamous carcinoma with liver metastases carries a particularly poor prognosis.

Observation:

• A patient with metastatic Siewert class III GEJ squamous carcinoma, initially progressing on chemotherapy, received combination immunotherapy with nivolumab and ipilimumab.
• Despite negative programmed death-ligand 1 (PD-L1) expression, microsatellite stable (MSS) status, and low tumor mutational burden, the patient demonstrated an unexpected and significant clinical benefit.

Findings:

• The patient experienced near-complete resolution of metastatic disease after approximately six months of nivolumab and ipilimumab treatment.
• Remarkable functional recovery was observed, including the removal of esophageal stent and feeding tube, indicating substantial disease regression.

Implications:

• This case highlights the potential efficacy of nivolumab and ipilimumab combination therapy in challenging GEJ cancer cases, even in the absence of predictive biomarkers.
• The findings underscore the importance of considering broader immunotherapy applications for difficult-to-treat malignancies.
• Further investigation into immunotherapy strategies for PD-L1 negative, MSS, and low tumor mutational burden GEJ cancers is warranted.