RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma

Abstract

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcɣR binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

“Sandwich Therapy”—Immunotherapy Plus Concurrent Chemoradiotherapy for Advanced Esophagogastric Junction Carcinoma: Report of Two Cases and Literature Review

“…Concurrent immunotherapy should be continued during chemoradiotherapy, but this triple combination therapy increases the intensity of treatment and raises safety concerns. However, several clinical trials ( 17 – 19 ) have used a combination of concurrent radiotherapy and PD-1 inhibitors for the treatment of locally advanced esophageal cancer, suggesting that triple combination therapy is a viable treatment modality for some patients with esophageal cancer. In addition, both patients were negative for PD-L1 expression, suggesting that some patients with low PD-L1 expression might benefit from the combination with immunotherapy.…”

Dose escalation based on 18F-FDG PET/CT response in definitive chemoradiotherapy of locally advanced esophageal squamous cell carcinoma: a phase III, open-label, randomized, controlled trial (ESO-Shanghai 12)

“…The detailed comparison is in Table 3 . Esophageal cancer is on the way to the era of immunotherapy, despite the footstone of chemoradiation in locally advanced disease [ 38 – 40 ]. Precise radiotherapy based on biology and imaging will provide new basis for individualized therapies in the future [ 41 ].…”

Comparison of Efficacy and Safety of Taxanes Plus Platinum and Fluorouracil Plus Platinum in the First-Line Treatment of Esophageal Cancer: A Systematic Review and Meta-Analysis

“…At present, there are multiple studies exploring the modes of neoadjuvant therapy, including neoadjuvant chemotherapy combined with immunotherapy and nCRT combined with immunotherapy, and some have achieved excellent results. We look forward to updated research data, which will continue to improve the existing treatment modes [ 56 , 57 ].…”