Dr. Kelly on Trials Evaluating Frontline Immunotherapy Combinations in ESCC

Ronan J. Kelly, MD, MBA, director, Oncology, the Charles A. Sammons Cancer Center, W. W. Caruth, Jr. Chair in Immunology, Baylor University Medical Center, discusses the variety of clinical trials investigating immunotherapy with or without chemotherapy in patients with esophageal squamous cell carcinoma (ESCC).

The phase 3 CheckMate 648 trial (NCT03143153) investigated the safety and efficacy of nivolumab (Opdivo) plus chemotherapy vs nivolumab plus ipilimumab (Yervoy) vs chemotherapy alone in patients with previously untreated advanced ESCC. One aim of this trial was to determine whether patients with ESCC could benefit from a chemotherapy-free regimen, Kelly says.

This trial showed objective response rates of 47%, 28%, and 27% in the nivolumab/chemotherapy, nivolumab/ipilimumab, and chemotherapy alone arms, respectively. Additionally, treatment with the immunotherapy combination led to a median overall survival of 12.7 months vs 10.7 months in the chemotherapy-alone arms. Nivolumab plus chemotherapy demonstrated a median OS of 13.2 months. Responses with nivolumab plus ipilimumab were durable, with a duration of response of 11.1 months vs 8.2 months and 7.1 months with nivolumab/chemotherapy and chemotherapy alone, respectively. These data support the use of the first dual immunotherapy treatment option for patients with ESCC who refuse chemotherapy or in whom a chemotherapy regimen may be difficult to tolerate, Kelly emphasizes.

In the frontline advanced ESCC setting, many trials are investigating other PD-1 inhibitors in combination with chemotherapy, Kelly adds. The phase 3 RATIONALE-306 trial (NCT03783442) is evaluating tislelizumab (BGB-A317) or placebo plus chemotherapy. The phase 3 ESCORT-1st trial (NCT03691090), conducted across 60 centers in China, evaluated camrelizumab (SHR-1210) plus chemotherapy and showed positive outcomes vs placebo plus chemotherapy in this population. Similarly, the phase 3 JUPITER-06 trial (NCT03829969) is investigating toripalimab plus chemotherapy, and the phase 3 ASTRUM-007 trial (NCT03958890) is evaluating serplulimab (HLX-10) plus chemotherapy. Additionally, the phase 3 ORIENT-15 trial (NCT03748134) will examine sintilimab or placebo plus chemotherapy across 66 sites in China and 13 sites outside of China.

The phase 3 KEYNOTE-590 trial (NCT03189719) further supports the use of chemoimmunotherapy in this population. This trial, which investigated frontline pembrolizumab (Keytruda) plus chemotherapy in patients with advanced ESCC, demonstrated a median OS of 12.6 months with pembrolizumab plus chemotherapy vs 9.8 months with chemotherapy alone.

The most effective first-line treatment options for metastatic ESCC are a PD-1 inhibitor plus chemotherapy, according to Kelly. However, nivolumab plus ipilimumab is an effective chemotherapy-free option for this population, Kelly concludes.