Dr. Mehta on Frontline and Adjuvant Treatments in ESCC

Rutika Mehta, MD, MPH, medical oncologist, Moffitt Cancer Center, discusses which patients with esophageal squamous cell carcinoma (ESCC) may benefit most from the different frontline treatment options available and highlights key treatment developments with adjuvant immunotherapy plus chemotherapy.

Dr. Mehta on Frontline Treatments in ESCC

Chemotherapy alone has long been the standard first-line treatment for patients with metastatic ESCC, Mehta says. However, the phase 3 KEYNOTE-590 (NCT03189719) and CheckMate 648 (NCT03143153) trials have brought 2 new immunotherapy options to the frontline setting, Mehta explains. In KEYNOTE-590, patients with ESCC who received pembrolizumab (Keytruda) plus chemotherapy had a median overall survival (OS) of 12.6 months vs 9.8 months in those who received placebo plus chemotherapy. Additionally, the median progression-free survival (PFS) in this population was 6.3 months with the chemoimmunotherapy regimen vs 5.8 months with placebo.

CheckMate 648 investigated 2 frontline combinations: nivolumab (Opdivo) plus chemotherapy and nivolumab plus ipilimumab (Yervoy), a chemotherapy-free regimen. Across all enrolled patients with ESCC, this trial showed a median OS of 13.2 months with nivolumab plus chemotherapy vs 10.7 months with chemotherapy alone. CheckMate 648 also demonstrated a median OS benefit with nivolumab plus ipilimumab in this population, at 12.7 months vs 10.7 months with chemotherapy alone.

A small subset of patients with ESCC is eligible to receive the chemotherapy-free regimen of ipilimumab plus nivolumab, and the ideal patients for this regimen are those with minimal symptoms, Mehta notes. In patients with de novo metastatic disease who have their esophagus in place and present with dysphasia, a chemotherapy-free regimen may not be the most beneficial, Mehta elaborates. In addition, patients with heavy metastatic disease burden, such as multiple liver lesions or other visceral metastases, are not ideal candidates for this approach, Mehta says. However, patients on surveillance after esophagectomy who have isolated liver lesions, for example, may benefit from ipilimumab plus nivolumab.

Dr. Mehta on Future Developments in Adjuvant ESCC Treatment

An important development in the field of ESCC is the incorporation of adjuvant treatment after chemoradiation and surgery for patients with locally advanced disease, Mehta says. Adjuvant nivolumab is a new SOC in this setting, Mehta notes, and future data may demonstrate that the combination of chemoradiation and immunotherapy improves survival outcomes for patients with ESCC, Mehta explains.