Sep 30

QP 36 - From Brachy to Beams to Biologics: Innovations in Esophageal and Liver Cancer

1213 - Long-Term Survival and Biomarker-Based Exploratory Analysis of Nimotuzumab Combined with SIB-IMRT in Locally Advanced Esophageal Cancer: Insights from a Phase II Clinical Trial

08:15am - 08:20am ET

Room 162

Presenter(s)

Xiaohan Zhao, MD, PhD - The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei

R. Cheng¹, S. Liu¹, X. Li¹, L. Wang¹, C. Han¹, and X. Zhao²; ¹Department of Radiation Oncology, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China, ²Department of Radiation Oncology, Fourth Hospital of Hebei Medical University,, Shijiazhuang, China

Purpose/Objective(s): In the phase II study of ChiCTR1900027936, the combination of nimotuzumab (a monoclonal antibody against epidermal growth factor receptor) and simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and biomarker-based exploratory analyses.

Materials/Methods: This single-arm, phase II trial enrolled 36 patients diagnosed with unresectable stage ?–IVA ESCC was conducted at the XX hospital between December 2018 and August 2021. Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-_C), the prescription dose was 50.4 Gy/28 fractions, concurrently, the planning target volume of gross tumor (PTV-_G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28 fractions. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen. The 1-, 3-, 5-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included the analysis of ctDNA-based biomarker expression and therapeutic efficacy.

Results: (1) With a median follow-up of 46.5 months (IQR 13.2–57.0), the 1-, 3-, 5-year OS and PFS rates were 77.8%, 55.6%, 52.3% and 63.9%, 47.2% and 36.2%, and the median OS and PFS were not reached and 23 months, respectively. (2) Disease recurrence occurred in 22 of 36 patients (55%), 11 (30.5%) had local regional recurrence(LRR), 8 (22.2%) experienced distant metastasis, and 3 (8.3%) experienced concurrent LRR and distant failure. (3) We collected 3 tumor tissue samples and 38 plasma samples during treatment, using a customized 340-gene panel. Among which, TP53 exhibited the highest mutation frequencies with 40%(8/20) before treatment and 27.8%(5/18) after treatment. The 4-year OS rates were 69.23% and 40% for patients with TP53-negative and those with persistent TP53 mutation after treatment, respectively. The 4-year PFS rates were 61.54% and 40%, respectively (HR 2.791, 95%CI: 0.618–12.614, P=0.1641; HR=2.390, 95%CI: 0.566–10.088, P=0.2215).(4)The detection rate of left shift (positive) of nucleosome positioning in the whole group before treatment was 61.9%, which decreased to 28.6% after treatment.

Conclusion: The updated survival outcomes showed promising efficacy of nimotuzumab plus SIB-IMRT in locally advanced ESCC. Persistent positivity for TP53 mutation after treatment may indicate a poorer prognosis and nucleosome positioning was a promising biomarker worthy of further exploration.