First-line tislelizumab + chemo improves OS in advanced/metastatic ESCC

First-line treatment with tislelizumab + chemotherapy significantly improves overall survival (OS) in patients with advanced or metastatic oesophageal squamous cell carcinoma (ESCC) compared with chemotherapy alone, according to an interim analysis of the RATIONALE-306* trial presented at ESMO GI 2022.

“[The] results of the RATIONALE-306 study support tislelizumab + chemo as a standard first-line therapy option for patients with advanced or metastatic ESCC,” said Dr Harry Yoon from Mayo Clinic in Rochester, Minnesota, US, who presented the study.

This global, double-blind trial enrolled 649 patients (74.9 percent Asian) with unresectable, locally advanced or metastatic ESCC who had no prior systemic treatment for advanced disease. Participants were randomized to receive either intravenous (IV) tislelizumab 200 mg Q3W (n=326, median age 64 years) or placebo (n=323, median age 65 years) in addition to investigator-chosen chemotherapy, which included cisplatin or oxaliplatin plus fluoropyrimidine (option A**) or paclitaxel (option B***). Patients continued treatment until disease progression, unacceptable toxicity, or study withdrawal. [ESMO GI 2022, abstract LBA-1]

As of data cut-off on February 28, 2022, patients who received tislelizumab + chemo had significantly improved OS than those who received chemo alone (median 17.2 vs 10.6 months; hazard ratio [HR], 0.66; p<0.0001).

The 12-month and 18-month OS rates were higher among those treated with tislelizumab + chemo compared with chemo alone (65.0 percent vs 44.9 percent [12-month] and 48.6 percent vs 34.5 percent [18-month]).

Improved median OS was observed in the tislelizumab + chemo arm vs the chemo-alone arm regardless of baseline programmed death-ligand 1 (PD-L1) expression status (median 16.6 vs 10.0 months; HR, 0.62; p=0.0020 and 16.7 vs 10.4 months; HR, 0.72 for patients with PD-L1 score of ≥10 or <10 percent, respectively).

The OS benefit was consistently observed with the tislelizumab + chemo arm vs the chemo-alone arm across all prespecified subgroups, such as geographic region, race, and investigator-chosen chemotherapy options, Yoon noted.

Patients treated with tislelizumab + chemo also demonstrated significantly improved median progression-free survival (PFS) compared with chemo alone (7.3 vs 5.6 months; HR, 0.62; p<0.0001).

The objective response rate (ORR) was significantly higher in the tislelizumab + chemo arm than the chemo-alone arm (63.5 percent vs 42.4 percent; odds ratio, 2.38; p<0.0001), with a longer median duration of response (7.1 vs 5.7 months).

Grade ≥3 adverse events (AEs) occurred in 66.7 percent of the patients in the tislelizumab + chemo arm and 64.5 percent in the chemo-alone arm, leading to death in 1.9 percent and 1.2 percent of the patients, respectively. Decreased neutrophil and white blood cell count, anaemia, and nausea were the most common AEs reported in both treatment arms.

The combination of tislelizumab and chemo showed a manageable safety profile, with no new safety signals identified, in patients with advanced or metastatic ESCC, Yoon noted.

“[Overall,] tislelizumab + chemo, as first-line treatment, demonstrated a statistically significant and clinically meaningful improvement in OS compared with chemo alone, in patients with advanced or metastatic ESCC,” said Yoon.

“[Moreover,] the OS benefit with tislelizumab + chemo was accompanied by significant improvements in PFS and ORR, with a more durable tumour response compared with [chemo alone],” he added.

*RATIONALE-306: A study of tislelizumab (BGB-A317) in combination with chemotherapy as first-line treatment in participants with advanced esophageal squamous cell carcinoma

**Option A: IV cisplatin 60–80 mg/m² or oxaliplatin 130 mg/m² Q3W plus 5-fluorouracil 750–800 mg/m² on days 1–5 Q3W or oral capecitabine 1,000 mg/m² BID on days 1–14

***Option B: IV cisplatin or oxaliplatin plus paclitaxel 175 mg/m² Q3W