Adjuvant S-1 ups survival in resected biliary tract cancer

Giving adjuvant S-1 to patients with curatively resected biliary tract cancer (BTC) significantly improves survival compared with observation following surgery, according to the ASCOT trial presented in the 2022 ASCO Gastrointestinal Cancers Symposium (GICS).  

“[While] capecitabine is usually used for patients with curatively resected BTC in [the] EU and US, no clear survival benefit has been shown in phase III trials,” said lead investigator Dr Masafumi Ikeda from the National Cancer Center Hospital East in Kashiwa, Japan.

“[Meanwhile,] S-1, an oral fluoropyrimidine derivative, has shown promising efficacy, with a mild toxicity profile, in patients with advanced BTC,” he added, explaining on the rationale in looking at the role of S-1 in the curatively resected BTC setting.

The open-label, multicentre, phase III trial involved 440 adult patients who had R0/R1 resection for adenosquamous carcinoma of the intrahepatic or extrahepatic bile duct, gallbladder or ampulla of Vater with an ECOG performance status of 0 or 1. They were randomized 1:1 to receive adjuvant S-1 or observation only, following their surgery. [GICS 2022, abstract 382]

Patients assigned to the adjuvant S-1 arm were treated with four cycles of oral S-1 chemotherapy 40 mg/m² twice daily based on a 4-week on, 2-week off dosing schedule; while those in the observation control arm did not receive any further anti-cancer therapy.

After a median follow-up of 45.4 months, overall survival (OS) was significantly longer in patients treated with adjuvant S-1 compared with surgery alone (hazard ratio [HR], 0.694; one-sided p=0.008).

At 3 years, 77.1 percent of patients in the adjuvant S-1 arm were still alive compared with 67.6 percent in the surgery alone arm. 

Moreover, the survival benefit was seen across all prespecified subgroups regardless of age, cancer type or stage, R factor, performance status, and serum CA19-9, in favour of the adjuvant S-1 arm.

In addition, the rate of relapse-free survival (RFS) was also significantly higher in patients who received S-1 than those in the control group at 3 years (62.4 percent vs 50.9 percent; HR, 0.797, 95 percent confidence interval [CI], 0.613–1.035).

“Adjuvant S-1 was well tolerated,” reported Ikeda. Common adverse events (AEs) of any grades (occurring at ≥20 percent frequency) among patients treated with adjuvant S-1 included myelosuppression, gastrointestinal toxicity, and skin hyperpigmentation. 

The main grade 3–4 AEs reported with adjuvant S-1 therapy included biliary tract infection (7.2 percent), fatigue (2.9 percent), diarrhoea (2.9 percent), and appetite loss (2.9 percent), he pointed out.

“Adjuvant S-1 therapy led to significantly longer survival than surgery alone in patients with resected BTC and [should be considered] the standard of care for [these patients],” Ikeda concluded.