Novartis’s tislelizumab phase-III trial data shows survival results in esophageal cancer

Novartis recently announced results from the phase-III Rationale 306 trial showing tislelizumab plus chemotherapy significantly improved the Overall Survival (OS) as a first-line treatment for adult patients with unresectable, locally advanced or metastatic Esophageal Squamous Cell Carcinoma (ESCC), regardless of PD-L1 status. Tislelizumab plus chemotherapy demonstrated a median OS of 17.2 months (CI, 15.8-20.1 months) versus 10.6 months (CI, 9.3-12.1 months) in patients receiving chemotherapy plus placebo and reduced the risk of death by 34 per cent (hazard ratio=0.66; CI, 0.54-0.80, p<0.0001). In collaboration with BeiGene, these data were presented during a late-breaking oral session at the 2022 European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer (Abstract #LBA-1), a company statement said.

In patients with PD-L1 score ≥10 per cent (secondary endpoint), tislelizumab plus chemotherapy showed a median OS of 16.6 months (CI, 15.3-24.4 months) versus 10.0 months (CI, 8.6-13.0 months) in patients receiving chemotherapy plus placebo and reduced risk of death by 38 per cent (HR=0.62; CI, 0.44-0.86, p=0.0020). In those with PD-L1 score <10 per cent (exploratory analysis), median OS with tislelizumab plus chemotherapy was 16.7 months (CI, 13.0-20.1 months) versus 10.4 months (CI, 9.1-13.0 months; HR=0.72; CI, 0.55-0.94). Survival benefit was consistent across all other subgroups, including race, geographical region and investigator choice of chemotherapy. Tislelizumab plus chemotherapy also significantly improved progression-free survival (7.3 months vs 5.6 months; HR=0.62; CI, 0.52-0.75, p<0.0001) and objective response rate (63.5% vs 42.4%; odds ratio=2.38, p<0.0001), the statement said.

It notified that the incidence of Treatment-Related Adverse Events (TRAEs) was similar in both arms. Most common TRAEs for tislelizumab plus chemotherapy versus chemotherapy were anemia (68% vs 61%), decreased neutrophils (78% vs 80%), decreased white blood cell count (55% vs 65%), decreased appetite (39% vs 38%), nausea (37% vs 42%) and peripheral sensory neuropathy (26% vs 21%).

Rationale 306 (NCT03783442) is a multi-regional phase-III, randomised, placebo-controlled, double-blind study of tislelizumab in combination with chemotherapy versus chemotherapy in patients with unresectable, locally advanced recurrent or metastatic ESCC. Approximately, 649 study participants were randomised 1:1 to receive either tislelizumab plus chemotherapy or chemotherapy plus placebo. The primary endpoint is OS in the all-comer intent-to-treat population. Secondary endpoints include OS in patients with PD-L1 score ≥10 per cent, progression-free survival, objective response rate, duration of response, health-related quality of life measures and safety.