A phase II clinical trial has demonstrated that adding immunotherapy to neoadjuvant chemoradiation can significantly improve outcomes for patients with locally advanced esophageal cancer. The study, published in Clinical Cancer Research, found that the combination of radiation, chemotherapy, and immunotherapy made tumors more amenable to surgical resection, leading to improved survival rates.
Yin Li, MD, director of section of esophageal and mediastinal oncology at the Chinese Academy of Medical Sciences and Peking Union Medical College, noted that fewer than half of patients with esophageal squamous cell carcinoma (ESCC) have resectable disease at the time of diagnosis due to lack of symptoms and early detection. The neoadjuvant treatment approach tested in this trial aims to make initially unresectable tumors resectable, offering patients a chance for a durable cancer-free state.
Study Details and Findings
The phase II trial enrolled patients aged 18-75 who received three steps of treatment: radiation with nab-paclitaxel (Abraxane) and cisplatin chemotherapy, followed by the immune checkpoint inhibitor tislelizumab (Tevimbra) plus chemotherapy, and then surgery if possible. Of the 30 patients enrolled, 20 underwent surgery and had complete resections.
Key findings from the study include:
- 19 of the 20 patients who underwent surgery experienced major pathologic responses.
- 13 of the 20 patients achieved complete pathologic responses.
- Patients who underwent surgery had significantly longer overall and progression-free survival compared to those who did not, with 82% and 72% reductions in the risk of death and progression, respectively, at one-year follow-up.
Li stated that the trial clearly demonstrated the effectiveness of combining chemoradiotherapy, chemoimmunotherapy, and surgery compared to nonsurgical management alone. The remarkable pathologic complete response and strong survival outcomes exceeded expectations.
The study also utilized circulating tumor DNA (ctDNA)-based liquid biopsies to monitor for relapse, providing valuable insights into the molecular landscape and minimal residual disease trajectory of these patients.
SCIENCE Trial Results
Preliminary results from the phase 3 SCIENCE trial, presented at the 2025 Gastrointestinal Cancers Symposium, further support the benefits of adding immunotherapy to chemoradiation. The trial demonstrated that adding sintilimab (Tyvyt) to neoadjuvant chemoradiotherapy (CRT) improved pathological complete response (pCR) rates compared to CRT alone in patients with resectable, locally advanced esophageal squamous cell carcinoma (ESCC).
The pCR rate was 60% in patients treated with sintilimab plus CRT, compared to 47.3% in those given CRT alone (OR vs sintilimab plus chemotherapy, 6; 95% CI, 2.3-17.8; P = .0005). Xuefeng Leng, MD, PhD, of the Department of Thoracic Surgery at Sichuan Cancer Hospital & Institute, suggested that neoadjuvant CRT combined with immunotherapy has the potential to become the new standard of care in the near future.
Limitations and Future Directions
Limitations of the phase II study include its small sample size and treatment discontinuations. Phase III trials are needed to validate these findings and explore the optimal sequencing of therapies. Similarly, while the SCIENCE trial results are promising, further data on event-free survival are needed to fully assess the benefits of sintilimab in combination with chemoradiotherapy.
Despite these limitations, the results from both trials suggest that incorporating immunotherapy into the neoadjuvant treatment of esophageal cancer can lead to significant improvements in patient outcomes.
