New Immunotherapy Combinations for Patients with Esophageal Cancer

For immediate release
January 16, 2024


Rachel Cagan Facci

ASCO Expert Perspective

 “Esophageal squamous cell carcinoma accounts for most esophageal cancer cases worldwide. This phase III trial demonstrates that dual immunotherapy plus chemotherapy with the novel checkpoint inhibitor, tiragolumab, improves progression free and overall survival without compromising safety,” said Pamela Kunz, MD, ASCO Expert. 

Study at-a-Glance 


Combination immunotherapy plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma


461 patients from five countries across Asia

Main Takeaway 

Dual immunotherapy plus chemotherapy prolongs survival in patients with advanced esophageal squamous cell carcinoma


  • Esophageal cancer is the eighth most commonly diagnosed cancer worldwide, and esophageal squamous cell carcinoma is the most common form of esophageal cancer – making up more than 80% of all esophageal cancers – with China accounting for approximately half of global esophageal squamous cell carcinoma disease burden.
  • Patients with locally advanced unresectable or metastatic esophageal squamous cell carcinoma generally have a poor prognosis, with 5-year survival rates reported as low as 5%.
  • The current first-line standard of care for systemic therapy for patients with advanced esophageal squamous cell carcinoma is checkpoint inhibitor plus platinum-based doublet chemotherapy, however, additional treatment strategies are needed to further improve patient outcomes.
  • Targeting TIGIT has been actively investigated as a new cancer immunotherapy in multiple cancer types. 
  • Tiragolumab is a human anti-TIGIT monoclonal antibody that may enhance antitumor responses when combined with other immunotherapies.
  • SKYSCRAPER-08 is the first phase III study to explore the efficacy and safety of tiragolumab in combination with atezolizumab plus chemotherapy vs. chemotherapy alone in patients with advanced esophageal squamous cell carcinoma in the first-line setting.


ALEXANDRIA, Va. —Results from a new phase III study found that combining PD-L1and TIGIT inhibitors plus chemotherapy in the first-line setting prolongs survival in an Asian population of patients with metastatic or locally advanced esophageal squamous cell carcinoma. This treatment combination has the potential to boost the body's ability to fight cancer and may ultimately lead to better outcomes for these patients with esophageal squamous cell carcinoma that cannot be surgically removed or has spread to other parts of the body. The research will be presented at the 2024 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium, taking place January 18-20 in San Francisco, California. 

About the Study

“Esophageal squamous cell carcinoma has a significant impact on patients’ functioning and quality of life, including symptoms such as trouble sleeping, weight loss, anxiety and depression, pain, and difficulty swallowing. Given the demographics of patients with esophageal cancer, the study was intended to focus on the Asian population,” said lead study author Chih-Hung Hsu, MD, PhD, from the National Taiwan University Hospital in Taipei, Taiwan 

The SKYSCRAPER-08 study evaluated the efficacy and safety of the addition of the T-cell immunoglobulin and ITM domain (TIGIT) inhibitor tiragolumab to the programmed cell death protein 1 (PD-L1) inhibitor atezolizumab in combination with chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with unresectable locally advanced, unresectable recurrent, or metastatic esophageal squamous cell carcinoma. Overall, 461 patients were enrolled at 67 centers in mainland China, South Korea, Thailand, Taiwan, and Hong Kong. The primary endpoints were independent review facility-assessed progression-free survival (PFS) and overall survival (OS).

Key Findings 

In this randomized, double-blind, placebo-controlled study, 229 were randomized to receive the immunotherapy combination plus chemotherapy and 232 patients were randomized to receive the placebo plus chemotherapy.

  • After a minimum survival follow-up of 6.5 months, the median independent review facility-assessed PFS was 6.2 months in patients who received the tiragolumab plus atezolizumab plus chemotherapy vs. 5.4 months in patients who received the placebo plus chemotherapy.
  • After a minimum survival follow-up of 14.5 months, the median OS was 15.7 months in patients who received the tiragolumab plus atezolizumab plus chemotherapy vs. 11.1 months in patients who received the placebo plus chemotherapy.
  • Overall, treatment-related side effects occurred in 98.2% of patients in both treatment arms. Most of the side-effects seen in both arms are those related to chemotherapy. 
  • Side effect of note in the tiragolumab plus atezolizumab and chemotherapy arm were immune-mediated rash (38.6%), immune-mediated hepatitis (35.1%), immune-mediated hypothyroidism (17.5%), infusion-related reaction (17.5%), and immune-related pneumonitis (7.5%). Most of the side effects of special interest were grade 1 or grade 2 and were easily manageable.

Next Steps  

Studies to investigate tiragolumab plus atezolizumab as a maintenance therapy following definitive chemoradiotherapy and the combination of tiragolumab plus atezolizumab with neoadjuvant chemoradiotherapy followed by surgery for locally advanced esophageal cancer are ongoing.

The study was funded by F. Hoffmann-La Roche Ltd and Genentech Inc. 

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