RATIONALE 302: Tislelizumab beats chemo in advanced ESCC

Treatment with tislelizumab led to a significantly improved overall survival (OS) in patients with advanced or metastatic oesophageal squamous cell carcinoma (ESCC) compared with chemotherapy in the second-line setting, according to the RATIONALE 302* study presented at ASCO 2021.

This global, phase III trial involved 512 patients with advanced or metastatic ESCC who had progressed during or after the first-line systemic treatment. Participants were randomly assigned in a 1:1 ratio to receive intravenous tislelizumab 200 mg every 3 weeks (median age 62.0 years, 84.8 percent male) or investigator’s choice of chemotherapy** (median age 63.0 years, 84.0 percent male). Patients continued treatment until disease progression, unacceptable toxicity, or study withdrawal. [ASCO 2021, abstract 4012]

At data cut-off, patients who received tislelizumab had a significantly improved median OS compared with those who received chemotherapy (8.6 vs 6.3 months; hazard ratio [HR], 0.70; one-sided p<0.0001).

In a subgroup of patients with vCPS** ≥10 percent, a significantly improved median OS was also observed in those treated with tislelizumab vs chemotherapy (10.3 vs 6.8 months; HR, 0.54; p=0.0006).

“[Of note,] survival benefit was consistently observed across predefined subgroups, including PD-L1 expression status, race, and region,” said lead author Professor Lin Shen from the Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) at Peking University Cancer Hospital & Institute in Beijing, China.

Tislelizumab recipients also achieved a longer median duration of response compared with the chemotherapy recipients (7.1 vs 4.0 months), with an objective response rate of 20.3 percent vs 9.8 percent (OR, 2.4).

Grade ≥3 treatment-emergent adverse events occurred at a lower rate in the tislelizumab arm than the chemotherapy arm (46.3 percent vs 67.9 percent), with fewer adverse events leading to treatment discontinuation (6.7 percent vs 13.8 percent). “Tislelizumab showed a favourable safety profile, … with no new safety signals identified,” Shen noted.

“[In conclusion, second-line treatment] with tislelizumab demonstrated statistically significant and clinically meaningful improvement in OS vs chemotherapy in advanced or metastatic ESCC patients whose tumour [had] progressed during or after first-line treatment,” said Shen.

“Tislelizumab [also] resulted in higher and more durable antitumour response, … and represents a potential new standard second-line treatment option for patients with advanced or metastatic ESCC,” she added.

*RATIONALE 302: A study of tislelizumab (BGB-A317) versus chemotherapy as second-line treatment in participants with advanced esophageal squamous cell carcinoma

**Chemotherapy: Intravenous paclitaxel 137–175 mg/m² Q3W or 80–100 mg/m² QW, docetaxel 75 mg/m² Q3W, or irinotecan 125 mg/m² on days 1 and 8, Q3W