Tislelizumab plus chemotherapy may be a new first-line treatment option for patients with PD-L1-positive, advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma, according to a presentation at the 2023 ASCO Gastrointestinal Cancers Symposium.
“Tislelizumab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival vs placebo plus chemotherapy in patients with PD-L1-positive gastric cancer or gastroesophageal junction adenocarcinomas,” said study presenter Markus H. Moehler, MD, PhD, of Johannes Gutenberg-University Clinic in Mainz, Germany.
Dr Moehler and colleagues also found that adding tislelizumab to chemotherapy improved responses and progression-free survival (PFS) in these patients.
These results come from the phase 3 RATIONALE-305 trial (ClinicalTrials.gov Identifier: NCT03777657). The trial enrolled 546 patients with PD-L1-positive, HER2-negative, unresectable, locally advanced or metastatic gastric/GEJ cancer.
Patients were randomly assigned to receive tislelizumab plus investigator’s choice of chemotherapy (n=274) or placebo plus chemotherapy (n=272). Chemotherapy consisted of oxaliplatin plus capecitabine or cisplatin plus fluorouracil. Tislelizumab was given at 200 mg every 3 weeks. In both arms, the initial treatment was 6 cycles, but patients could continue on treatment until progression or unacceptable toxicity.
Baseline characteristics were similar between the arms. The median age was 61 years in the tislelizumab arm and 62 years in the placebo arm. Most patients (70.4% and 73.9%, respectively) were men, and most (92.7% and 93.4%) received oxaliplatin plus capecitabine as chemotherapy. A minority (37% and 38%) had received prior adjuvant or neoadjuvant therapy.
The median overall survival (OS) was 17.2 months in the tislelizumab arm and 12.6 months in the placebo arm (hazard ratio [HR], 0.74; 95% CI, 0.59-0.94; P =.0056). The 12-month OS rate was 59.8% in the tislelizumab arm and 56.7% in the placebo arm. The 24-month OS rate was 38.3% and 24.9%, respectively.
The median PFS was 7.2 months in the tislelizumab arm and 5.9 months in the placebo arm (HR, 0.67; 95% CI, 0.55-0.83). The 12-month PFS rate was 33.8% in the tislelizumab arm and 18.9% in the placebo arm. The 24-month PFS rate was 22.3% and 8.7%, respectively.
The overall response rate was 50.4% in the tislelizumab arm and 43.0% in the placebo arm. The median duration of response was 9.0 months and 7.1 months, respectively.
Treatment-related adverse events (TRAEs) occurred in 97.1% of patients in the tislelizumab arm and 96.0% of patients in the placebo arm. Grade 3 or higher TRAEs occurred in 52.6% and 48.5%, respectively. There were 6 fatal TRAEs in the tislelizumab arm and 2 in the placebo arm.
“Tislelizumab plus chemotherapy had a manageable safety profile in this patient population, with no new safety signals identified,” Dr Moehler said. “The RATIONALE-305 results offer tislelizumab plus chemotherapy as a new first-line treatment option for patients with PDL-1-positive, unresectable, locally advanced or metastatic gastric or gastroesophageal cancer.”
Disclosures: This research was supported by BeiGene, Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Moehler MH, Kato K, Arkenau H-T, et al. RATIONALE-305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma. ASCO GI 2023. January 19-21, 2023. Abstract 286.