Phase 3 Study Shows Tislelizumab Improves Overall Survival in Esophageal Squamous Cell Carcinoma


In PD-L1-positive patients, tislelizumab improved median overall survival by 3.5 months with a 46% decrease in the risk of death compared with chemotherapy.

Treatment with tislelizumab was found to improve overall survival (OS) compared with chemotherapy in patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who had received prior systemic therapy, according to results from the randomized, global phase 3 RATIONALE 302 trial. The findings were presented at the 2021 American Society of Clinical Oncology Annual Meeting.

The primary endpoint of RATIONALE 302 was OS in the intent-to-treat population, with a key secondary endpoint of OS in programmed death-ligand 1 (PD-L1)-positive patients (vCPS ≥10%) and additional secondary endpoints of progression-free survival (PFS), overall response rate (ORR), duration of response (DoR), and safety endpoints. Tislelizumab, an investigational anti-PD-1 immune checkpoint inhibitor, improved median OS by 2.3 months versus chemotherapy—from 8.6 months to 6.3 months (p=0.0001), respectively.

Tislelizumab also showed a 30% decrease in the risk of death (HR=0.70, 95% CI: 0.57-0.85, p=0.0001). In PD-L1-positive patients, tislelizumab improved median OS by 3.5 months with a 46% decrease in the risk of death (HR=0.54, 95% CI: 0.36-0.79, p=0.0006).

"These data show that tislelizumab has the potential to help patients with esophageal squamous cell carcinoma—one of the deadliest types of cancers—live longer," said Jeff Legos, PhD, MBA, senior vice president and head of Oncology Drug Development at Novartis, in a press release. "We are excited about these results from the newest asset in our portfolio of transformational medicines and look forward to sharing these data with regulatory authorities, as we continue to explore the full potential of this uniquely designed anti-PD-1 antibody."

Tislelizumab also showed median PFS of 1.6 months compared to 2.1 months (HR=0.83, 95% CI: 0.67–1.01) with chemotherapy, as well as a higher and more durable anti-tumor activity (ORR, 20.3% vs. 9.8%; median DoR, 7.1 months vs. 4.0 months).

Treatment-related adverse events (TRAEs) caused discontinuation of therapy in 6.7% of patients who received tislelizumab versus 13.8% with chemotherapy. The most common all-grade TRAEs (≥10%) associated with tislelizumab were increased aspartate aminotransferase (11.4%), anemia (11%) and hypothyroidism (10.2%).

"Most patients with this type of esophageal cancer are diagnosed with advanced disease, resulting in a poor prognosis for this difficult-to-treat cancer," said Jaffer Ajani, MD, professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, in a press release. "The impact tislelizumab had on survival compared to chemotherapy in this study is highly meaningful and encouraging news for patients, caregivers and treating oncologists."


Novartis investigational checkpoint inhibitor tislelizumab met primary endpoint of overall survival in pivotal Phase III trial of esophageal cancer after systemic therapy. [news release]. June 4, 2021. Novartis. Accessed June 4, 2021.

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