2020 - Checkpoint Inhibition in Metastatic ESCC: Survival Outcomes and Opportunities for RT-IO Synergy

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 21

POSTER

Presenter(s)

Vincent Rothweiler, MD - Heinrich Heine University, Dusseldorf,

V. Rothweiler¹, C. Roderburg¹, M. Koeksal², W. Budach³, J. Fischer¹, I. Gencer², G. Lu⁴, Y. Li⁵, W. T. Knoefel¹, B. E. Jensen¹, T. Feldt¹, J. Neuwahl¹, and E. Boelke²; ¹Heinrich Heine University, Dusseldorf, Germany, ²University Hospital OWL Klinikum Bielefeld, Bielefeld, Germany, ³Department of Radiation Oncoloy, Heinrich Heine University, Dusseldorf, Germany, ⁴Yangzhou University, Yangzhou, China, ⁵Northern Jiangsu People's Hospital, Yangzhou, China

Purpose/Objective(s):

Metastatic esophageal squamous cell carcinoma (ESCC) is associated with poor prognosis. While systemic PD-1 inhibitors have reshaped first-line therapy, radiotherapy remains central for palliation and local control in thoracic oncology. Understanding how immunotherapy outcomes interact with radiotherapy indications is critical for radiation oncologists, particularly in the context of symptom management and potential RT-IO synergy.

Materials/Methods:

A systematic search (2015–2025) identified phase III randomized controlled trials comparing PD-1 inhibitors (pembrolizumab, nivolumab, camrelizumab, tislelizumab) with chemotherapy in advanced or metastatic ESCC. Hazard ratios (HRs) for overall survival (OS) were extracted and pooled using a fixed-effects model. Subgroup analyses were performed by PD-L1 expression, age, and geographic region. In addition, implications for radiotherapy integration were analyzed, including palliative RT for dysphagia and bleeding, and conceptual frameworks for RT-IO combinations.

Results:

Four phase III trials (KEYNOTE-590, CheckMate-648, ESCORT-1st, RATIONALE-306) were included. All demonstrated significant OS benefit for PD-1 inhibitor–based regimens. The pooled HR for OS was 0.65 (95% CI: 0.58–0.72), corresponding to a 35% risk reduction for death compared with chemotherapy. Patients with PD-L1 CPS =10 derived the greatest benefit (HR 0.62), but survival improvement was also observed in PD-L1 low populations (HR 0.79). Benefit was consistent across age groups and geographic regions. Immune-related adverse events occurred in ~10–15% of patients and were generally manageable. These systemic improvements redefine the context in which radiotherapy is applied: RT is increasingly reserved for symptom control, but future strategies may explore RT-IO combinations to enhance both local and systemic disease control

Conclusion:

PD-1 inhibitors significantly improve OS in advanced ESCC and establish a new systemic standard. For radiation oncologists, these findings highlight the evolving role of RT—shifting from routine palliation toward strategic integration with immunotherapy. Prospective studies should evaluate optimal sequencing, dose, and field design in RT-IO approaches, aiming to maximize local control while leveraging systemic immune activation.