Adjuvant S-1 prolongs survival among patients with resected biliary tract cancer

ByDevin McLaughlin

Adjuvant S-1 therapy significantly extended survival compared with surgery alone among patients with resected biliary tract cancer, according to results of a study conducted in Japan and presented at ASCO Gastrointestinal Cancers Symposium.

Perspective from Daneng Li, MD

“[Based on these results,] adjuvant S-1 therapy is considered to be standard of care for resected biliary tract cancer,” Masafumi Ikeda, MD, PhD, of National Cancer Center Hospital East in Kashiwa, Japan, said during a presentation.

Three-year study outcomes. — Data derived from Ikeda M, et al. Abstract 382. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan 20-22, 2022; San Francisco.

Rationale

The BILICAP trial established capecitabine as a standard adjuvant treatment for curatively resected biliary tract cancer, although results showed no statistically significant OS benefit compared with surgery alone in the intention-to-treat analysis of that study. The oral fluoropyrimidine derivative S-1 (Taiho Pharmaceutical) has shown encouraging efficacy and mild toxicity among patients with advanced biliary tract cancer and has become an established therapy in Japan for patients with resected pancreatic and gastric cancers, Ikeda said.

Methodology

The JCOG1202: ASCOT trial enrolled 440 adults with curatively resected biliary tract cancer at 38 Japanese hospitals. Researchers randomly assigned patients to no further anticancer treatment after surgery (n = 222) or four cycles of adjuvant S-1 dosed orally at 40 mg/m² twice daily in a 4-weeks-on, 2-weeks-off schedule (n = 218).

The surgery-alone and adjuvant S-1 treatment groups had similar patient characteristics, including age (median, 70 years vs. 68 years), percentage of men (68% vs. 74%) and resection status (R0, 85% vs. 86%; R1, 15% vs. 14%).

OS served as the primary endpoint, with RFS, adverse events and proportion of treatment completion as secondary endpoints. Researchers performed the primary analysis 3 years after enrollment concluded.

Key findings

Results showed significantly longer OS in the adjuvant S-1 group compared with the surgery-alone group (HR = 0.69; 95% CI, 0.51-0.93). Ikeda reported 3-year OS rates of 77.1% (95% CI, 70.9-82.1) with adjuvant S-1 vs. 67.6% (95% CI, 61-73.3) with surgery alone.

“The benefit of OS with adjuvant S-1 was consistent across almost all subgroups,” he said, including those based on age, performance status, cancer type and cancer stage.

Ikeda said researchers observed a “clear” but not statistically significant RFS benefit with adjuvant S-1 compared with surgery alone (HR = 0.79; 95% CI, 0.61-1.03). The adjuvant S-1 group had a higher 3-year RFS rate (62.4%; 95% CI, 55.6-68.4) than the surgery-alone group (50.9%; 95% CI, 44.1-57.2). Updated analysis of RFS with longer follow-up is necessary, Ikeda said.

The most common adverse events in the S-1 group included myelosuppression and gastrointestinal and skin toxicities. Grade 3 to grade 4 adverse events with the highest incidence included decreased neutrophil (14%), anemia (4%), diarrhea (2.9%), fatigue (2.9%) and appetite loss (2.9%).

Perspective

Daneng Li, MD

Biliary tract cancers are aggressive malignancies, and only about 20% of tumors are considered for surgical resection with curative intent. Recurrence rates remain high, and the need remains for effective adjuvant therapy to improve rates of RFS and OS while maintaining quality of life.

Previously, the BILCAP study demonstrated a positive effect of adjuvant therapy with capecitabine on OS compared with observation in adjusted intent-to-treat and per-protocol analyses, as well as a significant difference in RFS, while showing no significant difference in OS in an unadjusted ITT analysis. Although the study was performed in the United Kingdom and some concerns existed in terms of how this data would translate to Asian patients, capecitabine has been, for the most part, adopted as an option for patients with resected biliary tract cancer.

The current phase 3 study by Ikeda and colleagues investigated the role of S-1 in Asian patients with resected biliary tract cancer. The strength of this study was its demonstration of a statistically significant improvement in OS with adjuvant treatment with S-1 vs. surgical resection alone. However, although the trial showed a trend of better RFS with S-1 compared with surgical resection alone, this was not statistically significant. A further limitation of the study is the broader applicability of the results given the potential differences in toxicity profile of S-1 in Asian compared with non-Asian patients as reported in other S-1 trials.

Overall, this study further adds confidence to the positive activity of adjuvant fluoropyrimidine therapy for resected biliary tract cancer. Given that the landscape of advanced biliary tract cancer continues to evolve rapidly with several multiagent regimens showing promise in the metastatic setting, investigation of newer combination regimens in the earlier adjuvant setting should be performed.

Reference:

Primrose JN, et al. Lancet Oncol. 2019;doi:10.1016/S1470-2045(18)30915-X.

Daneng Li, MD

City of Hope

Disclosures: Li reports research funding to his institution from AstraZeneca and Brooklyn ImmunoTherapeutics, and a consultant role with/honoraria from Eisai, Exelixis, Genentech, Ipsen Biopharmaceuticals and Merck.

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Sources/Disclosures

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Source:

Ikeda M, et al. Abstract 382. Presented at: ASCO Gastrointestinal Cancers Symposium; Jan 20-22, 2022; San Francisco.

Disclosures: Ikeda reports honoraria from, a consultant/advisory role with and/or institutional research funding from AstraZeneca, Bayer Yakuhin, Eisai, Eli Lilly Japan, Novartis, Takeda, Taiho Pharmaceutical and several other pharmaceutical companies. Please see the abstract for all other researchers’ relevant financial disclosures.

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