Combining PD-L1 and TIGIT Inhibitors Plus Chemotherapy in Esophageal Cancer

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Results from the phase III SKYSCRAPER-08 study found that combining PD-L1 and T-cell immunoglobulin and ITM domain (TIGIT) inhibitors plus chemotherapy in the first-line setting extended 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 patients with unresectable or metastatic esophageal squamous cell carcinoma. The research was presented by Hsu et al at the 2024 ASCO Gastrointestinal Cancers Symposium (Abstract 245).

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, of the National Taiwan University Hospital in Taipei.

The SKYSCRAPER-08 study evaluated the efficacy and safety of the addition of the TIGIT inhibitor tiragolumab to the 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 and overall survival.

Key Findings 

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

After a minimum survival follow-up of 6.5 months, the median independent review facility–assessed progression-free survival was 6.2 months with tiragolumab, atezolizumab, and chemotherapy vs 5.4 months with placebo plus chemotherapy. After a minimum survival follow-up of 14.5 months, the median overall survival was 15.7 months in patients who received tiragolumab plus atezolizumab plus chemotherapy vs 11.1 months in patients who received 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 were related to chemotherapy. 

Side effects of note with tiragolumab plus atezolizumab and chemotherapy 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 2 and were easily manageable, according to the study authors.

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.

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, an ASCO Expert. 

Disclosure: The study was funded by F. Hoffmann–La Roche Ltd and Genentech Inc. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.