The European Commission has approved tislelizumab monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma after prior platinum-based chemotherapy.
The European Commission (EC) has approved tislelizumab (Tevimbra) monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior platinum-based chemotherapy.1
The regulatory decision was based on data from the phase 3 RATIONALE 302 trial (NCT03430843), which demonstrated that patients in the intention-to-treat (ITT) population who were administered tislelizumab (n = 256) experienced a statistically significant and clinically meaningful improvement in overall survival (OS) compared with those treated with physician’s choice of chemotherapy (n = 256; HR, 0.70; 95% CI, 0.57-0.85; P = .0001).2 Tislelizumab resulted in a median OS of 8.6 months (95% CI, 7.5-10.4) vs 6.3 months (95% CI, 5.3-7.0) with chemotherapy. The 12-month OS rates were 37.4% (95% CI, 31.4%-43.4%) and 23.7% (95% CI, 18.5%-29.3%), respectively.
“The global RATIONALE 302 trial demonstrated the anti–PD-1 antibody tislelizumab prolonged the survival of patients with locally advanced or metastatic ESCC who had received prior systemic treatment, with no new safety signals identified,” Florian Lordick, MD, director and professor of oncology of the University Cancer Center in Leipzig, Germany, stated in a news release.1 “The approval of tislelizumab in Europe is a noteworthy moment for patients, their caregivers and their physicians, due to the existing unmet need for new treatment options.”
The global, randomized, open-label, RATIONALE 302 study enrolled patients at least 18 years of age with a histologically confirmed diagnosis of ESCC who experienced tumor progression during or after first-line treatment for unresectable, locally advanced or metastatic ESCC.3 Patients needed to have at least 1 measurable/evaluable lesion per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate end organ function.
Key exclusion criteria included 2 or more prior systemic treatments for advanced/metastatic unresectable ESCC; a history of gastrointestinal perforation and/or fistula or aorto-esophageal fistula within 6 months of randomization; uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage; and prior treatment with anti–PD-1 or–PD-L1 therapies.
Patients were randomly assigned to receive 200 mg of intravenous tislelizumab once every 3 weeks or investigator’s choice of chemotherapy. Chemotherapy options consisted of paclitaxel at 135 mg/m2 to 175 mg/m2 once every 3 weeks, or 80 mg/m2 to 100 mg/m2 once per week; docetaxel at 75 mg/m2 once every 3 weeks; or irinotecan at 125 mg/m2 on days 1 and 8 of every 21-day cycle.
Along with the primary end point of OS, secondary end points included OS in the PD-L1–positive analysis set, overall response rate (ORR), progression-free survival, duration of response (DOR), health-related quality of life, and safety.
Additional data showed that among patients with a PD-L1 tumor area positivity (TAP) score of at least 10%, those treated with tislelizumab (n = 89) experienced a median OS of 10.3 months (95% CI, 8.5-16.1) compared with 6.8 months (95% CI, 4.1-8.3) for those given chemotherapy (n = 68; HR, 0.54; 95% CI, 0.36-0.79; P = .0006).2 Notably, OS benefits were also observed for tislelizumab for patients with a PD-L1 TAP score of less than 10% (HR, 0.82; 95% CI, 0.62-1.09) and unknown TAP scores (HR, 0.67; 95% CI, 0.41-1.12).
In the ITT population, patients treated with tislelizumab achieved an ORR of 20.3% (95% CI, 15.6%-25.8%) compared with 9.8% (95% CI, 6.4%-14.1%) for those given chemotherapy. The complete response rates were 2.0% and 0.4%, respectively. The median DOR was 7.1 months (95% CI, 4.1-11.3) for tislelizumab vs 4.0 months (95% CI, 2.1-8.2) for chemotherapy.
Safety findings for tislelizumab were consistent with prior trials, and the EC approval was supported by data from 1972 patients who received tislelizumab monotherapy across 7 clinical trials.1
In RATIONALE 302, patients treated with tislelizumab experienced lower rates of treatment-related adverse effects (TRAEs; 73.3%) compared with chemotherapy (93.8%).2 The rates of grade 3 or higher TRAEs for tislelizumab and chemotherapy were 18.8% and 55.8%, respectively, and the rates of serious TRAEs were 14.1% for tislelizumab and 19.6% for chemotherapy. The most common any-grade TRAEs in the experimental arm included increased aspartate aminotransferase (11.4%), anemia (11.0%), and hypothyroidism (10.2%).
TRAEs led to treatment discontinuation for 6.7% of patients in the tislelizumab arm vs 13.8% of patients in the chemotherapy arm.