KEY TAKEAWAYS
- The RATIONALE 306 (BGB-A317) phase 3 trial investigated TIS, an anti-PD-1 antibody, plus chemotherapy compared to placebo plus chemotherapy in patients with advanced or metastatic ESCC who had not received prior systemic treatment for advanced disease.
- The study’s primary aim was to determine the effect of TIS plus chemotherapy on OS compared to placebo plus chemotherapy.
- Adults with advanced or metastatic ESCC were randomly assigned to receive either TIS 200 mg IV once every 3 weeks (Arm A) or placebo IV Q3W (Arm B).
- In the interim analysis of the non-Asian subgroup, TIS plus chemotherapy significantly improved OS compared to placebo plus chemotherapy.
- More patients in Arm A than in Arm B encountered at least one treatment-related adverse event (TRAE; 94.0% vs 88.5%).
- The study concluded that patients with advanced or metastatic ESCC in the non-Asian subgroup who received 1L TIS plus chemotherapy had a statistically significant longer overall survival.
Compared to placebo plus chemotherapy (PBO + chemo), TIS, an anti-programmed cell death protein 1 (PD-1) antibody, plus chemotherapy as 1L therapy significantly improved overall survival (OS) in patients with advanced or metastatic ESCC at the interim analysis of phase 3, double-blind RATIONALE-306 study (NCT03783442) while maintaining a tolerable safety profile. The information presented comes from regions other than Asia. TIS 200 mg IV once every 3 weeks (Q3W) (Arm A) or PBO IV Q3W (Arm B) with platinum + fluoropyrimidine or platinum + paclitaxel until disease progression by INV per RECIST v1.1, intolerable toxicity, or withdrawal was given to adults with advanced or metastatic ESCC who had not received prior systemic treatment for advanced disease. In the study’s primary analysis, OS was the primary outcome. PFS, ORR, and DoR by INV per RECIST v1.1 were considered secondary objectives, along with OS in the programmed death-ligand 1 score of 10% and safety.
The non-Asian proportion of randomized patients was 25.1%, or 163 individuals (Arm A, n = 83; Arm B, n = 80). At the time of data discontinuation (February 28, 2022) in the non-Asia subgroup, the median trial follow-up time was 16.0 months (mo) in Arm A and 8.4 mo in Arm B. In comparison to Arm B, Arm A had better overall survival (median 16.3 vs 9.0 months; unstratified HR 0.66 [95% CI 0.45, 0.96]) and progression-free survival (PFS) (median 7.7 vs 5.5 months; unstratified HR 0.59 [95% CI 0.41, 0.83]). The ORR in Arm A was greater than that in Arm B (61.4% vs 41.3%, odds ratio 2.27 [95% CI 1.21, 4.25]), and the median DoR was greater in Arm A than in Arm B (7.1 months [95% CI 5.6, 9.6] vs 5.7 months [95% CI 3.8, 8.2]). Overall, more patients in Arm A than in Arm B encountered at least one treatment-related adverse event (TRAE; 94.0% vs 88.5%), more patients in Arm A suffered significant TRAEs (25.3% vs 17.9%), and more patients in Arm A discontinued treatment as a result of treatment-emergent AEs (42.2% vs 35.9%). Patients in Arm A and Arm B experienced a similar rate of TRAEs of grade 3 (56.6% vs 52.6%) and TRAEs resulting in mortality (1.2% vs 1.3%). Patients with advanced or metastatic ESCC in the non-Asia subgroup who received 1L TIS plus chemotherapy had a statistically significant longer overall survival than those who received PBO plus chemotherapy, with a tolerable risk of adverse events.
Source:https://meetings.asco.org/abstracts-presentations/216098
Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT03783442
Eric Raymond, Richard Hubner, Evgeny Gotovkin, Lucjan Wyrwicz, Eric Van Cutsem, Paula Jimenez-Fonseca, Roberto Pazo-Cid, Jianming Xu, Ken Kato, Aiyang Tao, Lei Wang, Yanyan Peng, Liyun Li, Harry H. Yoon/Randomized, global, phase 3 study of tislelizumab (TIS) + chemotherapy (chemo) versus placebo (PBO) + chemo as first-line (1L) treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC) (RATIONALE-306): Non-Asia subgroup/J Clin Oncol 41, 2023 (suppl 4; abstr 340) DOI10.1200/JCO.2023.41.4_suppl.340
