Tislelizumab Plus Chemo Yields Survival Benefit Vs Chemo in Advanced ESCC

The phase 3 RATIONALE 306 trial showed improved overall survival for patients receiving tislelizumab plus chemotherapy vs placebo and chemotherapy for unresectable, locally advanced or metastatic esophageal squamous cell carcinoma regardless of PD-L1 status.

Overall survival (OS) had been significantly improved when tislelizumab was added to chemotherapy for first-line treatment for unresectable locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) despite PD-L1 status, according to results from the phase 3 RATIONALE 306 trial (NCT03783442).

The median OS was 17.2 months (95% CI, 15.8-20.1) in the tislelizumab arm and 10.6 months (95% CI, 9.3-12.1) in the placebo arm. This translated to a reduction in risk of death of 34% (HR, 0.66; 95% CI, 0.54-0.80; P <.0001). The results from the updated analysis were presented at the 2022 European Society of Medical Oncology Congress on Gastrointestinal Cancer.

“These data, which show tislelizumab plus chemotherapy extended patients’ lives by a median of more than 6 months, are a promising outcome in the treatment of this aggressive cancer,” Ken Kato, MD, chief of Head and Neck Medical Oncology at the National Cancer Center Hospital in Tokyo, Japan, said in the press release. “Importantly, the significant overall survival benefit was observed across all patient subgroups in the trial, indicating that tislelizumab plus chemotherapy may be a viable treatment option for patients regardless of their PD-L1 score.”

A total of 649 patients were enrolled and were randomized 1:1 to receive either tislelizumab plus chemotherapy or chemotherapy plus placebo. In the tislelizumab arm, patients received 60 mg/m2 to 80 mg/m2 of intravenous cisplatin on day 1; 1000 mg/m2 of oral capecitabine on days 1 to 14; 175 mg/m2 of intravenous paclitaxel on day 1; 750 mg/m2 to 800 mg/m2 of intravenous fluorouracil on days 1 to 5; 130 mg/m2 of intravenous oxaliplatin on day 1; and 200 mg of intravenous tislelizumab every 3 weeks, respectively. In the placebo arm, patients received the same chemotherapy regimen plus a placebo.

Median OS for those with a PD-L1 score of 10% or more—the trial’s secondary end point—was 16.6 months (95% CI, 15.3-24.4) in the tislelizumab arm and 10.0 months (95% CI, 8.6-13.0) in the placebo arm, translating to a 38% reduction in risk of death (HR, 0.62; 95% CI, 0.44-0.86; P = .0020). For those who had a PD-L1 score of less than 10%, the median OS was 16.7 months (95% CI, 13.0-20.1) in the tislelizumab arm and 10.4 months in the placebo arm (95% CI, 9.1-13.0; HR, 0.72; 95% CI, 0.55-0.94). Of note, survival was similar across all subgroups including race, geographical region, and investigator choice chemotherapy.

Improvements in progression-free survival were also observed with a median of 7.3 months in the tislelizumab arm and 5.6 months in the placebo arm (HR, 0.62; 95% CI, 0.52-0.75; P <.0001). Additionally, an improved objective response rate was reported, including 63.5% vs 42.4% in the tislelizumab and placebo arms, respectively (OR, 2.38; P <.0001).

Treatment-related adverse effects included anemia (68% vs 61%), decreased neutrophil count (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%) in the tislelizumab and placebo arms, respectively.

“The prognosis for ESCC remains poor, with a 5-year survival rate of just 5%, and patients are in need of more treatment options, especially in earlier lines of therapy,” Jeff Legos, executive vice president of Global Head of Oncology & Hematology Development at Novartis, concluded. “These results add to the growing body of evidence demonstrating the potential for tislelizumab to help patients with esophageal cancer and reinforce our commitment to studying tislelizumab alone and in synergistic combinations across additional tumor types that may benefit from an immunotherapy.”

Reference

New phase III data show Novartis tislelizumab significantly extended median overall survival by more than 6 months in first-line advanced esophageal cancer in combination with chemotherapy. News Release. Novartis. June 30, 2022. Accessed July 1, 2022. https://bit.ly/3y6dlgl