Tislelizumab plus chemo gives survival advantage over chemo in advanced CCHS
The Phase 3 RATIONALE 306 trial showed improved overall survival for patients receiving tislelizumab plus chemotherapy compared to placebo plus chemotherapy for unresectable, locally advanced or metastatic esophageal squamous cell carcinoma, regardless of disease status. or PD-L1 status.
According to the results of RATIONALE 306 phase 3 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. This translated into a 34% reduced risk of death (HR, 0.66; 95% CI, 0.54-0.80; P <.0001 the results of updated analysis were presented at>European Society of Medical Oncology Gastrointestinal Cancer Congress 2022.
“These data, which show that tislelizumab plus chemotherapy prolonged patients’ lives by more than 6 months on average, are a promising result in the treatment of this aggressive cancer,” said Ken Kato, MD, chief of the 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 recruited and randomized 1:1 to receive either tislelizumab plus chemotherapy or chemotherapy plus placebo. In the tislelizumab arm, patients received cisplatin 60 mg/m2 to 80 mg/m2 intravenously on day 1; 1000 mg/m2 oral capecitabine on days 1-14; 175 mg/m2 intravenous paclitaxel on day 1; 750 mg/m2 to 800 mg/m2 intravenous fluorouracil on days 1-5; 130 mg/m2 intravenous oxaliplatin on day 1; and 200 mg intravenous tislelizumab every 3 weeks, respectively. In the placebo arm, patients received the same chemotherapy regimen plus a placebo.
The median OS for people with a PD-L1 score of 10% or greater – the trial’s secondary endpoint – 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, resulting in a 38% reduction in the risk of death (HR, 0.62; 95% CI , 0.44-0.86; P = .0020). For those with a PD-L1 score 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 (95% CI, 9.1-13.0; RR, 0.72; 95% CI, 0.55-0.94). Of note, survival was similar across all subgroups, including race, geographic region, and investigator-chosen chemotherapy.
Improvements in progression-free survival were also seen 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
Treatment-emergent adverse events included anemia (68% vs 61%), neutrophil count decreased (78% vs 80%), white blood cell count decreased (55% vs 65%), appetite (39% versus 38%), nausea. (37% vs 42%) and peripheral sensory neuropathy (26% vs 21%) in the tislelizumab and placebo arms, respectively.
“The prognosis for CCHS remains poor, with a 5-year survival rate of only 5%, and patients need more treatment options, especially in the first lines of treatment,” Jeff Legos, vice -Executive Chairman of Global Head of Oncology & Hematology Development at Novartis, concluded. “These results add to the growing body of evidence demonstrating the potential of tislelizumab to help patients with esophageal cancer and reinforce our commitment to study tislelizumab alone and in synergistic combinations on other tumor types that may to benefit from immunotherapy.
New Phase III data show that Novartis’ tislelizumab significantly prolonged median overall survival by more than 6 months in first-line advanced esophageal cancer in combination with chemotherapy. Press release. Novartis. June 30, 2022. Accessed July 1, 2022. https://bit.ly/3y6dlgl