Originally published by 2 Minute Medicine^® (view original article). Reused on AccessMedicine with permission.

1. Median overall survival was 17.2 months in the tislelizumab group versus 10.6 months in the placebo group (HR 0.66).

2. Both groups experienced similar rates of grade 3 or worse treatment-related adverse events.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Current first-line treatment options for esophageal cancer have limited efficacy, but recent research has shown that anti-PD-1 antibodies in combination with chemotherapy led to improved overall survival. This research however examined a particular chemotherapy regimen (cisplatin plus fluorouracil), limiting its generalizability. The study assessed the efficacy and safety of first-line treatment with tislelizumab (IgG4 monoclonal antibody with high affinity for PD-1) plus investigator-chosen chemotherapy compared with placebo plus chemotherapy in patients with advanced or metastatic esophageal squamous cell carcinoma. The primary outcome was overall survival (OS), and secondary outcomes included progression-free survival (PFS), overall response rate (ORR), duration of response (DoR), safety, and health-related quality of life. This study found the median OS was 17.2 months in the tislelizumab group versus 10.6 months in the placebo group (HR 0.66), and the median PFS was 7.3 months versus 5.6 months respectively (HR 0.62). With regards to ORR, patients treated with tislelizumab plus chemotherapy had an ORR of 63% compared to 42% treated with a placebo (OR 2.38). Both groups experienced similar rates of grade 3 or worse treatment-related adverse events, with the most common being decreased neutrophil count (31% in the tislelizumab group vs 33% in the placebo group), decreased white blood cell count (11% vs 16%), and anemia (15% vs 13%). 29% of the patients in the tislelizumab group versus 19% in the placebo group had treatment-related emergent adverse events that led to treatment discontinuation. The strengths of this study included the randomized, placebo-controlled design and enrollment of many patients, whereas its limitations include unbalanced demographics. Overall, treatment with tislelizumab plus chemotherapy for advanced or metastatic esophageal squamous cell carcinoma has shown some improvement in efficacy compared to using chemotherapy with a placebo.

Click to read the study in Lancet

Click to read an accompanying editorial in Lancet

Relevant Reading: Tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (RATIONALE-302): a randomized phase III study

In-Depth [randomized controlled trial]:

This global, randomized, double-blinded, placebo-controlled, phase 3 study recruited 649 adults with locally advanced/metastatic esophageal squamous cell carcinoma and randomized them into tislelizumab 200mg IV q3weeks (326 patients) or placebo (323), together with investigator chosen chemotherapy regimen (platinum-based with either fluoropyrimidine, capecitabine or paclitaxel). Patients were enrolled regardless of the expression status of PD-L1, but that was assessed retrospectively. Tumour response was assessed through radiological imaging by a blinded independent review committee. The median study follow-up time was 16.3 months in the tislelizumab group and 9.8 months in the placebo group. 55% of patients were treated with platinum plus paclitaxel and 45% were treated with a platinum plus fluoropyrimidine. The median OS was 17.2 months (95%CI, 15.8-20.1) in the tislelizumab group versus 10.6 months (95%CI, 9.3-12.1) in the placebo group, with an HR of 0.66 (95%CI, 0.54-0.80, p<0.0001). Post-hoc analysis showed no significant interaction between treatment effect and PD-L1 status. The median PFS was 7.3 months (95%CI, 6.9-8.3) in the tislelizumab group versus 5.6 months (95%CI, 4.9-6.0) in the placebo group with an HR of 0.62 (95%CI, 0.52-0.75, p<0.0001). With regards to ORR, patients treated with tislelizumab plus chemotherapy had an ORR of 63% compared to 42% treated with placebo, OR 2.38 (95%CI, 1.73-3.27, p<0.0001). Both groups experienced similar rates of grade 3 or worse treatment-related adverse events (around 65%), with the most common being decreased neutrophil count (31% in the tislelizumab group vs 33% in the placebo group), decreased white blood cell count (11% vs 16%), and anemia (15% vs 13%). 29% of patients in the tislelizumab group versus 19% in the placebo group had treatment-related emergent adverse events that led to treatment discontinuation. Overall, treatment with tislelizumab plus chemotherapy for advanced or metastatic esophageal squamous cell carcinoma has shown some improvement in efficacy compared to using chemotherapy with a placebo.

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