Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial

Nakachi, Kohei; Konishi, Masaru; Nomura, Shosaku; Katayama, Hiroshi; Kataoka, Tomoko; Todaka, Akiko; Yanagimoto, Hiroaki; Kobayashi, Shogo; Shimada, Kazuaki; Takahashi, Yu; Shimizu, Yasuhiro; Ueno, Makoto; Ishii, Hiroshi; Furuse, Junji; Okamura, Keiya; Kawamoto, Yasuyuki; Katanuma, Akio; Unno, Michiaki; Soejima, Hirofumi; Yamaguchi, Hironori; Takahashi, Akiko; Ikeda, Masafumi; Yanagibashi, Hiroo; Kato, Naoya; Okusaka, Takuji; Sakamoto, Yoshihiro; Kojima, Yasushi; Higuchi, Ryota; Sasahira, Naoki; Sano, Keiji; Nakagohri, Toshio; Sunakawa, Yu; Morinaga, Soichiro; Kumamoto, Yusuke; Sugimori, Kazuya; Nomura, Tetsuya; Shibuya, Kazuto; Makino, Isamu; Yamazaki, Kentaro; Mizuno, Nobumasa; Kamata, Ken; Wada, Hiroshi; Gotoh, Kunihito; Sekimoto, Mitsugu; Ajiki, Tetsuo; Nakamura, Ikuo; Miki, Ikuya; Nagano, Hiroaki; Ohta, Kouji; Okabayashi, Takehiro; Furukawa, Masayuki; Fujimori, Nao

doi:10.1016/s0140-6736(22)02038-4

Cited by 107 publications

(69 citation statements)

References 21 publications

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“…In the BILCAP trial, extrahepatic CCA was present in 64% of the patients and 47% had lymph node metastases 8,9. Similarly, in the recent ASCOT trial that showed the benefit of adjuvant S-1, 56% had extrahepatic CCA and 40% had lymph node metastases 10. In the PRODIGE-12 trial that compared adjuvant gemcitabine plus oxaliplatin versus observation, 36% had extrahepatic CCA and 37% had lymph node metastases; this trial also did not meet its primary endpoint and failed to suggest the clinical benefit of gemcitabine-based chemotherapy in the subgroup of patients with lymph node metastases 7.…”

Section: Discussionmentioning

confidence: 96%

“…[8,9] Similarly, in the recent ASCOT trial that showed the benefit of adjuvant S-1, 56% had extrahepatic CCA and 40% had lymph node metastases. [10] In the PRODIGE-12 trial that compared adjuvant gemcitabine plus oxaliplatin versus observation, 36% had extrahepatic CCA and 37% had lymph node metastases; this trial also did not meet its primary endpoint and failed to suggest the clinical benefit of gemcitabine-based chemotherapy in the subgroup of patients with lymph node metastases. [7] The single-arm SWOG S0809 trial, which included a similar patient population (all extrahepatic CCA and gallbladder cancer; among patients with extrahepatic CCA, R1 resection in 35%, and lymph node-positive in ~78%) to the current trial, investigated gemcitabine plus CAP followed by radiation with concurrent CAP; the 2-year OS rate, the primary endpoint of the SWOS S0809 trial, was 68% in the extrahepatic CCA subgroup (n = 54), which is comparable to ours (77.8% in the GemCis group and 71.0% in the CAP group).…”

Section: Discussionmentioning

confidence: 99%

“…In the recent ASCOT trial, S-1, an oral fluoropyrimidine, showed significant improvement in overall survival (OS) compared with surveillance. [10] The reasons for these conflicting results among studies are not well understood. A potential explanation is the inclusion of heterogeneous patient populations in terms of the anatomical origin of the tumor and disease status including lymph node metastases.…”

Section: Introductionmentioning

confidence: 99%

“…Accordingly, adjuvant CAP is now considered a standard treatment for resected BTC. In the recent ASCOT trial, S-1, an oral fluoropyrimidine, showed significant improvement in overall survival (OS) compared with surveillance 10. The reasons for these conflicting results among studies are not well understood.…”

Section: Introductionmentioning

confidence: 99%

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Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial

Jeong

Kim

et al. 2023

Hepatology

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Background and Aims: The effectiveness of gemcitabine-based adjuvant chemotherapy is unclear in cholangiocarcinoma. We investigated the role of adjuvant gemcitabine plus cisplatin (GemCis) in a homogeneous group of high-risk patients with resected, lymph node-positive extrahepatic cholangiocarcinoma. Approach and Results: Adenocarcinoma of perihilar or distal bile duct with regional lymph node metastasis who underwent curative-intent surgery (R0/ R1) was eligible. Patients were randomized to receive GemCis (gemcitabine 1000 mg/m 2 , cisplatin 25 mg/m 2 on days 1 and 8) or capecitabine (1250 mg/ m 2 twice daily on days 1-14) every 3 weeks for 8 cycles. Primary endpoint was disease-free survival. Secondary endpoints were overall survival and safety. All p values are 1 sided and were considered significant if <0.1.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial

Jeong

Kim

et al. 2023

Hepatology

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“…Three patients achieved partial or complete remission after S-1 monotherapy, suggesting that S-1 could be used as an alternative therapy if standard first-line chemotherapy drugs were not tolerated. Results from a recent large trial of Japanese patients undergoing BTC resection showed a significant increase in both three-year OS (77.1% vs. 67.6%) and three-year relapse-free survival (62.4% vs. 50.9%) for patients treated with S-1 compared to those who did not receive it ( 27 ). Results from another trial investigating the efficacy of combined chemotherapy with S-1 and cisplatin in the treatment of metastatic or recurrent BTC showed an overall ORR of 30% and a median OS of 8.7 months ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review

Zhang

Liu

et al. 2023

Front. Immunol.

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Gallbladder cancer (GBC) and cholangiocarcinoma are common cancers of the biliary system and are associated with a poor prognosis. Surgery and chemotherapy provide limited benefit to patients with advanced biliary tract carcinoma. Novel immunotherapies and molecularly targeted therapies are more effective options; however, few patients benefit and drug resistance is a concern. Here, we report five cases of advanced GBC with either high programmed death-ligand 1 (PD-L1) expression or a high tumor mutation burden (TMB-H). The patients were treated with a combination therapy of tislelizumab and S-1. The tumors were effectively controlled in most patients. One patient developed immune-related pneumonia (irP) during treatment, which resolved after hormone therapy, and the patient underwent surgery. Tislelizumab and S-1 were administered again after surgery; however, recurrent irP required discontinuation, and the tumor progressed after drug withdrawal. These cases demonstrate that combined therapy of anti-programmed cell death protein-1 (PD-1) antibodies and S-1 is a safe and effective regimen with few side effects for GBC patients, especially for sensitive populations (patients with TMB-H, microsatellite instability, deficient mismatch repair, or high expression of PD-L1). To our knowledge, this is the first time that tislelizumab in combination with S-1 has been used to treat patients with advanced GBC.

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Adjuvant Chemotherapy and Outcomes in Older Adult Patients With Biliary Tract Cancer

Gbolahan,

Zhi,

Liu

et al. 2024

JAMA Netw Open

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ImportanceThe association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated.ObjectiveTo describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC.Design, Setting, and ParticipantsThis retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment.ExposuresAdjuvant chemotherapy vs observation following BTC resection.Main Outcomes and MeasuresThe primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias.ResultsBetween 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P &lt; .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P &lt; .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P &lt; .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P &lt; .001) were associated with worse OS.Conclusions and RelevanceIn this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.

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Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial

Cited by 107 publications

References 21 publications

Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial

Adjuvant gemcitabine plus cisplatin versus capecitabine in node-positive extrahepatic cholangiocarcinoma: the STAMP randomized trial

Case report: Preliminary response to tislelizumab plus S-1 in patients with metastatic gallbladder carcinoma: A report of five cases and a literature review

Adjuvant Chemotherapy and Outcomes in Older Adult Patients With Biliary Tract Cancer

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