Among patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, those with a baseline ECOG performance status of 1 experienced worsened patient-reported outcomes (PROs), clinical trial findings have shown.
Findings from a post hoc analysis of the phase 3 RATIONALE-305 trial were presented at the 2026 Gastrointestinal Cancers Symposium.
The post hoc analysis included patients treated during the study with either the experimental regimen of Tevimbra (tislelizumab-jsgr) plus chemotherapy or placebo plus chemotherapy.
Glossary
- ECOG Performance Status: This is a scale from 0 to 5 that doctors use to assess how a patient's disease is affecting their daily living abilities. It helps them determine if a patient is healthy enough for a specific treatment, like chemotherapy or a clinical trial. Lower scores indicate greater abilities.
- Overall Survival (OS): It refers to the length of time from either the date of diagnosis or the start of treatment that a patient remains alive.
- Progression-Free Survival (PFS): This measures the length of time during and after treatment that a patient lives with the disease, but the cancer does not get worse.
- Objective Response Rate (ORR): This is the percentage of patients whose cancer shrunk or disappeared after treatment.
- Duration of Response (DOR): Once a treatment successfully shrinks a tumor (as measured by the ORR above), the duration of response tracks how long that improvement lasts before the cancer begins to grow again.
Notably, when patients were stratified by ECOG performance status (0 versus 1), the analysis revealed no statistically significant differences across gastric/GEJ-specific symptom domains on the EORTC QLQ-STO22 questionnaire, including dietary restrictions (mean, 86.9 for ECOG 0 versus 86.0 for ECOG 1), dysphagia (89.5 versus 88.6), pain/discomfort (81 versus 78.2) and upper GI symptoms (88.5 versus 86.9), suggesting ECOG performance status may not fully capture baseline gastric/GEJ cancer–specific symptom burden.
Conversely, patients with baseline ECOG performance status of 1 had lower odds of reporting favorable PROs compared with those with an ECOG performance status of 0. Specifically, an ECOG performance status of 1 was associated with significantly lower odds of reporting better global health status/quality of life (GSH/QOL; 72.5 for ECOG 0 versus 68 for ECOG 1), physical functioning (89.8 versus 87.6) and pain on the EORTC QLQ-C30 questionnaire. A trend toward worse outcomes was also observed for role functioning (89.3 versus 86.6), although this did not reach statistical significance. No significant associations were observed for constipation (87 versus 86), diarrhea (92.8 versus 93.9) or fatigue (79.4 versus 77.5).
“Among patients with first-line gastric/GEJ, those with [a] baseline ECOG performance status [of] 1 reported significantly worse GHS/QOL, physical functioning and pain [versus] those with [an] ECOG performance status [of] 0, irrespective of treatment arm. Multivariable regression analyses confirmed a lower probability of achieving better PRO scores for patients with ECOG performance status 1 compared with ECOG performance status 0,” lead study author Dr. Marcia Cruz-Correa concluded in her presentation of the results. “These results suggest that integrating baseline PROs into eligibility and/or stratification criteria may improve risk stratification, support more patient-centered trial design and foster more meaningful patient-clinician dialogue at treatment initiation.”
What design characteristics were included in the RATIONALE-305 trial?
In December 2024, the U.S. Foos and Drug Administration (FDA) approved Tevimbra in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with unresectable or metastatic, HER2-negative gastric or GEJ adenocarcinoma whose tumors express PD-L1 (≥1). This regulatory decision was supported by prior data from RATIONALE-305, which showed that treatment with Tevimbra plus chemotherapy led to a statistically significant and clinically meaningful improvement in overall survival (OS) at 15 months compared with 12.9 months for placebo plus chemotherapy.
RATIONALE-305 was a randomized, double-blind, phase 3 study that enrolled patients with previously untreated, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.Eligible patients had histologically confirmed disease, HER2-negative disease, no prior systemic therapy for advanced disease, an ECOG performance status of 0 or 1, and at least one measurable or non-measurable lesion.
Patients were randomly assigned to receive Tevimbra plus chemotherapy or placebo plus chemotherapy for up to six cycles, followed by Tevimbra or placebo with optional capecitabine beginning in cycle 7 and beyond.
The primary end point of the overall trial was OS in patients with a PD-L1 combined positive score of at least 5% and in the intention-to-treat population. Secondary end points included progression-free survival, objective response rate, duration of response, safety and PROs.
The PRO analysis included 932 randomly assigned patients who completed baseline EORTC QLQ-C30 and QLQ-STO22 questionnaires. Patients were analyzed according to baseline ECOG performance status, with data pooled across treatment arms. Profile analyses were conducted to evaluate differences in overall levels and patterns across 11 PRO domains, and logistic regression sensitivity analyses were performed to identify PRO domains associated with ECOG performance status.
“Ongoing work in RATIONALE-305 is assessing the extent to which ECOG performance status meaningfully differentiates PRO trajectories over time and by treatment to further inform how ECOG performance status and PROs can be jointly leveraged in advanced gastric or gastroesophageal junction adenocarcinoma,” Cruz-Correa expressed.
References
- “Associations between ECOG performance status and patient-reported outcomes in patients with gastric or gastroesophageal junction (GC/GEJC) adenocarcinoma: Post hoc analysis from the RATIONALE-305 trial” by Dr. Marcia Cruz-Correa et al.,J Clin Oncol.
- “Tevimbra approved in U.S. for first-line treatment of gastric and gastroesophageal junction cancers in combination with chemotherapy,” news release; https://ir.beigene.com/news/tevimbra-approved-in-u-s-for-first-line-treatment-of-gastric-and-gastroesophageal-junction-cancers-in-combination/cedb475b-fcfe-47a4-8afe-8a501d9cf849/
- “Tislelizumab in combination with chemotherapy as first-line treatment in adults with inoperable, locally advanced, or metastatic gastric or gastroesophageal junction carcinoma,” https://clinicaltrials.gov/study/NCT03777657
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