Episode 12: The RATIONALE-306 study solidifies checkpoint inhibition therapy in ESCC
Presented by Prof Marc Van den Eynde (Cliniques Universitaires Saint-Luc) and Prof Eric Van Cutsem (University Hospitals Leuven)
Prof Eric Van Cutsem from University Hospitals Leuven and Prof Marc Van den Eynde from Cliniques Universitaires Saint Luc are discussing the role of immunotherapy in treating metastatic oesophagal squamous cell carcinoma (ESCC).
The RATIONALE-306 study, a global trial involving both East Asian and Western patients, evaluates the efficacy of combining the investigator’s choice doublet chemotherapy with or without tislelizumab, a PD-L1 antibody also possessing ADC properties. Notably, this was a first-line treatment and patient inclusion was not based on PD-L1 status, as CPS testing was not used for enrichment. The primary endpoint of this phase 3 study was OS.
Results demonstrate a clear positive outcome, with median OS increasing from 10.6 to over 17 months with the combination of chemo doublet and tislelizumab. Subgroup analysis reveals a particularly pronounced benefit among PD-L1 enriched subgroups. While tislelizumab exhibited immune-related toxicity typical of PD-L1 antibodies, no new safety concerns emerged.
Experts delve into the comparative efficacy of tislelizumab versus other checkpoint inhibitors like nivolumab or pembrolizumab, though caution against direct cross-trial comparisons. Nevertheless, RATIONALE-306 solidifies the role of checkpoint inhibition in first-line treatment for metastatic ESCC.
Looking forward, the future of immunochemotherapy in these patients may involve combining different classes of immune-oncology agents, as is observed in other cancer types. The SKYSCRAPER-08 study, for instance, demonstrated the benefit of combining a PD-L1 antibody and TIGIT inhibitor with chemotherapy over chemotherapy alone. Unfortunately, this study lacked a third arm combining the PD-L1 antibody alone with chemotherapy, which would have allowed for a clearer assessment of the added benefit of the TIGIT inhibitor. Further research is warranted in this regard, yet it remains evident that combined immune-oncology treatment represents a valuable option for specific patient subgroups.
In conclusion, immune checkpoint inhibition and double immunotherapy represent enduring pillars in the management of ESCC.
References:
Xu J et al., (2023) Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study. The Lancet oncology Volume 24, Issue 5, P483-495
Hsu C-H. et al. (2024) SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC). J Clin Oncol 42, (suppl 3; abstr 245)
