KEY TAKEAWAYS
- The BGB-A317 phase 3 trial aimed to assess the eeficacy of TIS vs PBO + CT in pts with advanced ESCC.
- The primary endpoint was OS.
- Improved OS with TIS + CT in PD-L1 TAP ≥1%; TAP and CPS scores showed high concordance.
Tislelizumab (TIS) (an anti–PD-1 antibody) + chemotherapy (CT) demonstrated significant overall survival (OS) benefit vs placebo (PBO) + CT as first-line (1L) therapy for advanced esophageal squamous cell carcinoma (ESCC) in all randomized patients (pts; stratified HR 0.66) and pts with PD-L1 Tumor Area Positivity (TAP) score ≥10% (stratified HR 0.62). Sustained survival benefit was observed at 3 yrs follow-up.
Eric Raymond and the team reported exploratory analyses of OS by PD-L1 expression status and consesus of PD-L1 TAP and combined positive score (CPS).
Researchers performed an inclusive analysis of adults with advanced ESCC who were randomized (1:1) to IV TIS 200 mg or PBO every 3 weeks alongside investigator-chosen CT (platinum + fluoropyrimidine or platinum + paclitaxel) until disease progression or intolerable toxicity. The primary endpoint was OS. Tissue samples underwent staining using the VENTANA PD-L1 (SP263) assay. PD-L1 expression was initially assessed by tumor proportion score (TPS) and subsequently re-evaluated post hoc by CPS. OS was evaluated using various PD-L1 cutoffs, with investigation into the concordance between TPS and CPS at multiple cutoff points. Interclass correlation coefficient (ICC) and Cohen’s Kappa were calculated to assess agreement.
Results indicated that of 649 pts who were randomized in the study, PD-L1 status was evaluable in 542 pts for TAP and 537 pts for CPS. The distribution of PD-L1 TAP scores was as given here: 223 pts (34%) had a TAP score ≥10%, 135 pts (21%) had a score between 5 to <10%, 123 pts (19%) had a score between 1 to <5%, and 61 pts (9%) had a score <1%. Followed by a minimum follow-up period of 3 years, the analysis pinpointed that OS was significantly enhanced in TIS + CT vs PBO + CT in PD-L1 subgroups with TAP scores ≥1%. Whereas, the OS outcomes in the subgroup with TAP score <1% were limited due to corresponding sample size.
The OS results based on TAP and CPS scores reflected similar findings. The ICC between TAP and CPS was 0.85 (95% CI 0.80–0.88), which suggested a high degree of alignment between these two methods of assessing PD-L1 expression. Furthermore, TAP and CPS scores demonstrated substantial concordance in terms of overall percentage agreement and Cohen’s Kappa statistic, underscoring the consistency in their assessment of PD-L1 expression levels in the study population.
The findings concluded that TIS + CT as a promising first-line therapy for advanced ESCC. Concordance between TAP and CPS scoring methods affirms their reliability in assessing PD-L1 expression .
The trial was sponsored by BeiGene.
Source: https://cslide.ctimeetingtech.com/esmogi24hybrid/attendee/confcal/show/session/34
Clinical Trial: https://clinicaltrials.gov/study/NCT03783442
Raymond E, Xu J, Kato K, et al. (2024). “Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT in advanced or metastatic esophageal squamous cell carcinoma (ESCC): PD-L1 biomarker analysis from RATIONALE-306.” Presented at ESMO-GI 2024, (Abstract 395MO)
