Oct 01

QP 19 - GI 4: Quick Pitch: Enhancing Efficacy for Esophageal Cancer and Radiation Responders for Rectal Cancer

1109 - Radiotherapy followed by Systemic Therapy and Tislelizumab in MSS Rectal Cancer with Unresectable Metastases: Results of the MIRACLE-2 Study

08:10am - 08:15am PT

Room 154

Presenter(s)

Zhen Zhang, MD, PhD - Fudan University Shanghai Cancer Center, shanghai, shanghai

M. L. Zhou¹, L. Shen¹, Z. Shan², H. Zhang¹, J. Wan¹, W. Yang¹, Y. Chen¹, S. Zhou¹, D. Luo², Z. Ye², W. He², Y. Yang², Y. Chen², C. Zhou³, Q. Li², X. Li², F. Xia¹, and Z. Zhang¹; ¹Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, ²Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, ³Department of Cancer Prevention, Fudan University Shanghai Cancer Center, Shanghai, China

Purpose/Objective(s):

MSS tumors account for 95% of metastatic colorectal cancer and are characterized by the hyporesponsiveness of immunotherapy. Systemic therapy has been reported to promote immunotherapy response. The addition of radiotherapy may further improve the efficacy as it can overcome the hyporesponsiveness and decrease tumor burden. MIRACLE-2 aims to assess the safety and efficacy of radiotherapy combined with systemic therapy and Tislelizumab in the first-line treatment of MSS unresectable metastatic rectal cancer (RC).

Materials/Methods:

MIRALCE-2 was a prospective, single arm, phase 2 study. The main inclusion criteria included MSS locally advanced RC with a distance of =10 cm from the anus by MRI evaluation, and with unresectable metastases. Eligible patients (pts) were treated with radiotherapy including hypofractionated radiotherapy (HFRT) for primary lesions and HFRT or stereotactic body radiotherapy (SBRT) for metastatic lesions, followed by FOLFOX plus bevacizumab and Tislelizumab for RAS/BRAF-mutant pts, or FOLFIRI plus cetuximab and Tislelizumab for RAS and BRAF-wild pts. Reassessment was performed every two months. For patients converted to resectable disease, surgical resections w/o local ablative therapies of primary and metastatic lesions were performed. Otherwise, systemic treatment was administered until disease progression or intolerable toxicity. The primary endpoint was the rate of early tumor shrinkage (ETS), which was defined as = 20% reduction of target lesions’ diameter at 8 weeks since the initiation of systemic therapy. The secondary endpoints included disease control rate (DCR), duration of response, overall survival (OS), progression-free survival (PFS) and toxicities.

Results:

From March 2023 to November 2024, 45 pts were enrolled and 38 were evaluable. At baseline, 76.3% of pts were male, median age was 56 years (range 30-73), 57.9% had liver metastases (mets), 5.3% had lung mets, and 36.8% had both liver and lung mets. 50.0% primary tumors had RAS/BRAF mutations. The ETS rate was 84.2%. The DCR reached 92.1%. 6 pts received primary tumor resection, and 9 pts received both primary and metastatic tumor resections. 15.8% (6/38) pts remained NED. Median PFS was 9.2 months. Median OS has not yet reached. No grade 5 adverse events occurred. The most common treatment-related adverse events (TRAEs) in all grades were fatigue (81.6%), neutropenia (65.8%) and thrombocytopenia (52.6%). The most frequent grade 3/4 TRAEs were neutropenia (34.2%) and thrombocytopenia (21.1%).

Conclusion:

Combination treatment of radiotherapy, systemic therapy and Tislelizumab demonstrated a high ETS rate and a manageable safety profile in MSS unresectable metastatic RC. Translational study to identify predictive biomarkers is ongoing. Clinical trial information: NCT05359406.