Dr. Saeed on Biomarkers That Influence Treatment Decisions in ESCC

Anwaar Saeed, MD, associate professor, medicine, chief, Gastrointestinal Medical Oncology, University of Pittsburgh Medical Center, discusses biomarkers that signal the potential efficacy of frontline immunotherapy regimens in patients with advanced esophageal squamous cell carcinoma (ESCC).

The tissue-agnostic biomarkers microsatellite instability (MSI)–high disease and mismatch repair deficiency (dMMR) should be tested for in every solid tumor type and can also drive first-line treatment approaches in ESCC, Saeed says. If patients have these biomarkers, they can receive standard-of-care chemotherapy with either nivolumab (Opdivo), per the phase 3 CheckMate 648 trial (NCT03143153), or pembrolizumab (Keytruda), per the phase 3 KEYNOTE-590 trial (NCT03189719), Saeed explains. In CheckMate 648, patients with advanced ESCC were randomized 1:1:1 to receive nivolumab plus chemotherapy, nivolumab plus ipilimumab (Yervoy), or chemotherapy alone. The patients in the nivolumab/chemotherapy arm achieved a median overall survival (OS) of 13.2 months vs 10.7 months in the chemotherapy alone arm. In KEYNOTE-590, patients with advanced ESCC were randomized 1:1 to either pembrolizumab plus chemotherapy or placebo plus chemotherapy. In this trial, patients who received pembrolizumab achieved a median OS of 12.6 months vs 9.8 months with placebo.

Additionally, with the May 2022 FDA approval of ipilimumab plus nivolumab for patients with ESCC, this chemotherapy-free regimen is another potential frontline treatment option. This approval was based on additional findings from CheckMate 648, in which the patients who received nivolumab plus ipilimumab achieved a median OS of 12.7 months vs 10.7 months in those who received chemotherapy alone.

PD-L1 expression is another relevant biomarker in ESCC and other upper gastrointestinal cancers and should be tested for in all patients regardless of their histology, Saeed notes. If patients have high PD-L1 expression, they should receive chemotherapy with either pembrolizumab or nivolumab, Saeed says.

Patients with ESCC can also be tested for tumor mutational burden (TMB), although most patients with MSI-high disease will also have high TMB, Saeed explains. The definition of high TMB for every disease type, including ESCC, is still unclear, Saeed notes. However, patients with higher TMB along with high PD-L1 expression may benefit most from the use of immunotherapy regimens, Saeed concludes.