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Clinical Trial
. 2025 Feb 10;43(5):536-544.
doi: 10.1200/JCO-24-01383. Epub 2024 Dec 13.

SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers

Affiliations
Clinical Trial

SWOG S1815: A Phase III Randomized Trial of Gemcitabine, Cisplatin, and Nab-Paclitaxel Versus Gemcitabine and Cisplatin in Newly Diagnosed, Advanced Biliary Tract Cancers

Rachna T Shroff et al. J Clin Oncol. .

Abstract

Purpose: SWOG S1815 was a randomized, open label phase III trial, evaluating gemcitabine, nab-paclitaxel, and cisplatin (GAP) versus gemcitabine and cisplatin (GC) in patients with newly diagnosed advanced biliary tract cancers (BTCs).

Methods: Patients with newly diagnosed locally advanced unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) and gallbladder carcinoma (GBC), were randomly assigned 2:1 to either GAP (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, and nab-paclitaxel 100 mg/m2 intravenously once per day on days 1 and 8 of a 21-day cycle) or GC (gemcitabine 1,000 mg/m2 and cisplatin 25 mg/m2 intravenously once per day on days 1 and 8 of a 21-day cycle).

Results: Among 452 randomly assigned participants, 441 were eligible and analyzable, 67% with ICC, 16% with GBC, and 17% with ECC. There was no significant difference in overall survival (OS) between GAP versus GC. Median OS with GAP was 14.0 months (95% CI, 12.4 to 16.1) and 13.6 months with GC (95% CI, 9.7 to 16.6); hazard ratio (HR), 0.91 (95% CI, 0.72 to 1.14); P = .41. Median progression-free survival (PFS) was similar between groups with median PFS for GAP being 7.5 months (95% CI, 6.4 to 8.5) versus 6.3 months for GC (95% CI, 4.4 to 8.2); HR, 0.89 (95% CI, 0.71 to 1.12); P = .32. In exploratory subset analyses, the OS and PFS benefits of GAP versus GC treatment were greater in locally advanced disease compared with metastatic disease, although not statistically significant (interaction P = .14 for OS and P = .17 for PFS). Moreover, GAP versus GC showed greater improvement in PFS among participants with GBC than those with ICC or ECC (interaction P = .01), but not OS (interaction P = .28).

Conclusion: The addition of a taxane in the GAP regimen to the standard gemcitabine-cisplatin regimen did not improve OS in newly diagnosed BTC. More toxicity was encountered with GAP versus GC.

Trial registration: ClinicalTrials.gov NCT03768414.

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Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Rachna T. Shroff

Consulting or Advisory Role: Merck, AstraZeneca, Boehringer Ingelheim, Genentech, Jazz Pharmaceuticals, Merus

Research Funding: Merck, Exelixis, Rafael Pharmaceuticals, Bristol Myers Squibb, Immunovaccine, Seagen, Novocure, Nucana, Loxo/Lilly, Faeth Therapeutics, NGM Biopharmaceuticals, Actuate Therapeutics, Lisata, Fujifilm, Compass Therapeutics

Gentry King

Consulting or Advisory Role: AstraZeneca, Ipsen

Aaron J. Scott

Stock and Other Ownership Interests: Johnson & Johnson/Janssen

Consulting or Advisory Role: Exelixis, QED Therapeutics, Pfizer

Research Funding: Exelixis, Genentech, Incyte, Five Prime Therapeutics, Merck

Travel, Accommodations, Expenses: Exelixis, QED Therapeutics

Mitesh J. Borad

Consulting or Advisory Role: Lynx Group, Merck, Imvax, Zymeworks, Kriya Therapeutics, BJ Bioscience, Senti Biosciences, Tempus, Genentech

Research Funding: Senhwa Biosciences (Inst), MedImmune (Inst), Agios (Inst), Halozyme (Inst), Celgene (Inst), Sillajen (Inst), Eisai (Inst), Taiho Pharmaceutical (Inst), EMD Serono (Inst), Isis Pharmaceuticals (Inst), Incyte (Inst), QED Therapeutics (Inst), Puma Biotechnology (Inst), Adaptimmune (Inst), Merck Serono (Inst), RedHill Biopharma (Inst), Basilea (Inst), AstraZeneca (Inst), ZielBio (Inst), Relay Therapeutics (Inst), Kinnate Biopharma (Inst), Biond Biologics (Inst), Qurient (Inst)

Laura Goff

Consulting or Advisory Role: QED Therapeutics, Exelixis, Boehringer Ingelheim, Athenum Consulting, Relay Therapeutics, Merck, Bristol Myers Squibb Foundation, Jazz Pharmaceuticals, AstraZeneca

Research Funding: Bristol Myers Squibb (Inst), Agios (Inst), ASLAN Pharmaceuticals (Inst), BeiGene (Inst), Basilea (Inst), Merck (Inst)

Khalid Matin

Honoraria: Taiho Oncology, Bristol Myers Squibb/Pfizer

Consulting or Advisory Role: University of California

Travel, Accommodations, Expenses: Bristol Myers Squibb/Pfizer

Amit Mahipal

Consulting or Advisory Role: AstraZeneca/MedImmune, Taiho Oncology, Guardant Health, Elevar Therapeutics

Speakers' Bureau: AstraZeneca, Taiho Oncology

Research Funding: Taiho Pharmaceutical

Aparna Kalyan

Honoraria: Samumed

Consulting or Advisory Role: Exelixis, BTG, Boston Scientific, Incyte, Genentech, AstraZeneca, Elevar Therapeutics

Speakers' Bureau: Exelixis, Boston Scientific, Genentech/Roche, AstraZeneca

Research Funding: Bristol Myers Squibb (Inst), AstraZeneca (Inst)

Milind M. Javle

Honoraria: QED Therapeutics, Incyte, TransThera Biosciences, Merck, EMD Serono/Merck, AstraZeneca/MedImmune

Consulting or Advisory Role: QED Therapeutics, Oncosil, Incyte, Mundipharma, AstraZeneca, Merck, EMD Serono, Basilea Pharmaceutical

Other Relationship: Rafael Pharmaceuticals, Incyte, Pieris Pharmaceuticals, Merck, Merck Serono, Novartis, Seagen, BeiGene, QED Therapeutics, Bayer

Benjamin Tan

Research Funding: Eisai (Inst), Exelixis (Inst), Merck Serono (Inst), Bristol Myers Squibb (Inst), AstraZeneca (Inst), Adaptimmune (Inst), Tyme (Inst), Agios (Inst), Genentech/Roche (Inst), Tvardi Therapeutics (Inst), AbbVie (Inst)

Puneet Cheema

Employment: Fairview Health Services

Stock and Other Ownership Interests: Bristol Myers Squibb, Pfizer, ImmunityBio

Anuj Patel

Consulting or Advisory Role: Eisai

Research Funding: Analysis Group (Inst)

Travel, Accommodations, Expenses: Eisai

Renuka Iyer

Consulting or Advisory Role: Lexicon, Novartis, Eisai, Merck, Bayer, Advanced Accelerator Applications, Exelixis, Sun Pharma, QED Therapeutics, Ipsen, Sandoz, Tersera, AstraZeneca, Incyte, Genentech

Research Funding: Genentech/Roche (Inst), Ipsen (Inst), Lilly (Inst), Merck (Inst), Taiho Pharmaceutical (Inst), Cleveland BioLabs (Inst), Novartis (Inst)

Other Relationship: Genentech, Replimune, AstraZeneca

R. Katie Kelley

Consulting or Advisory Role: Agios (Inst), AstraZeneca (Inst), Merck (Inst), Kinnate Biopharma, Exelixis/Ipsen (Inst), Regeneron, Tyra Biosciences, Compass Therapeutics, Elevar Therapeutics, J-Pharma, Moderna Therapeutics, GlaxoSmithKline, Jazz Pharmaceuticals

Research Funding: Lilly (Inst), Exelixis (Inst), Novartis (Inst), Bristol Myers Squibb (Inst), MedImmune (Inst), Merck Sharp & Dohme (Inst), Agios (Inst), AstraZeneca (Inst), Adaptimmune (Inst), Taiho Pharmaceutical (Inst), Bayer (Inst), QED Therapeutics (Inst), EMD Serono (Inst), Partner Therapeutics (Inst), Genentech/Roche (Inst), Surface Oncology (Inst), Relay Therapeutics (Inst), Loxo/Lilly (Inst), Servier (Inst), Compass Therapeutics (Inst), Tyra Biosciences (Inst)

Travel, Accommodations, Expenses: AstraZeneca, Merck

Jaykumar Thumar

Stock and Other Ownership Interests: Pfizer, Iovance Biotherapeutics

Honoraria: Cardinal Health

Consulting or Advisory Role: Cardinal Health

Travel, Accommodations, Expenses: Cardinal Health

Anthony El-Khoueiry

Honoraria: Bristol Myers Squibb, Roche/Genentech, Eisai, Merck, Agenus, Exelixis, AstraZeneca/MedImmune, Servier, Senti Biosciences, Qurient, Terumo, Elevar Therapeutics

Consulting or Advisory Role: Bristol Myers Squibb, Eisai, Roche, Merck, Exelixis, Agenus, AstraZeneca/MedImmune, Servier, Senti Biosciences, Qurient, Terumo, Elevar Therapeutics, Genentech

Research Funding: AstraZeneca, Astex Pharmaceuticals, Fulgent Genetics, Auransa

Travel, Accommodations, Expenses: Affimed Therapeutics

E. Gabriela Chiorean

Consulting or Advisory Role: Ipsen, Pfizer, G1 Therapeutics, Astellas Pharma, Merus, Bristol Myers Squibb/Celgene, IgM Biosciences, Regeneron, BPGbio

Research Funding: Boehringer Ingelheim (Inst), Merck (Inst), AADi (Inst), FibroGen (Inst), Lonza (Inst), BioMed Valley Discoveries (Inst), Roche (Inst), Gilead/Forty Seven (Inst), Novartis (Inst), Erasca Inc (Inst), Mirati Therapeutics (Inst), Genentech (Inst), Affini-T Therapeutics (Inst)

Travel, Accommodations, Expenses: G1 Therapeutics, Merus

Howard Hochster

Stock and Other Ownership Interests: Compass Therapeutics

Consulting or Advisory Role: Processa Pharmaceuticals, Takeda

Expert Testimony: Natera

Travel, Accommodations, Expenses: Takeda

Other Relationship: Seagen

Philip A. Philip

Honoraria: Bayer, Ipsen, Incyte, Taiho Pharmaceutical, Astellas Pharma, BioNTech SE, Novocure, TriSalus Life Sciences, Servier, Seagen

Consulting or Advisory Role: Celgene, Ipsen, Merck, TriSalus Life Sciences, Daiichi Sankyo, SynCoreBio, Taiho Pharmaceutical

Speakers' Bureau: Incyte

Research Funding: Bayer (Inst), Incyte (Inst), Merck (Inst), Taiho Pharmaceutical (Inst), Novartis (Inst), Regeneron (Inst), Genentech (Inst), Halozyme (Inst), Lilly (Inst), Merus (Inst), BioNTech SE (Inst)

Uncompensated Relationships: Rafael Pharmaceuticals, Caris MPI

No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
CONSORT diagram. AE, adverse event; GAP, gemcitabine, nab-paclitaxel, and cisplatin; GC, gemcitabine and cisplatin.
FIG 2.
FIG 2.
(A) OS by treatment arm. (B) PFS by treatment arm. GAP, gemcitabine, nab-paclitaxel, and cisplatin; GC, gemcitabine and cisplatin; OS, overall survival; PFS, progression-free survival.
FIG 3.
FIG 3.
(A) OS by disease site and treatment arm. (B) PFS by disease site and treatment arm. (C) OS by disease stage and treatment arm. (D) PFS by disease stage and treatment arm. Ex chol, extrahepatic cholangiocarcinoma; Gall, gallbladder carcinoma; GAP, gemcitabine, nab-paclitaxel, and cisplatin; GC, gemcitabine and cisplatin; Int chol, intrahepatic cholangiocarcinoma; OS, overall survival; PFS, progression-free survival.

References

    1. Valle JW, Kelley RK, Nervi B, et al. : Biliary tract cancer. Lancet 397:428-444, 2021 - PubMed
    1. Kelley RK, Ueno M, Yoo C, et al. : Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 401:1853-1865, 2023 - PubMed
    1. Oh D-Y, Ruth He A, Qin S, et al. : Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid 1:EVIDoa2200015, 2022 - PubMed
    1. Wei D, Cheng X, Du C, et al. : Stroma-targeted nanoparticles that remodel stromal alignment to enhance drug delivery and improve the antitumor efficacy of nab-paclitaxel in pancreatic ductal adenocarcinoma models. Nano Today 45:101533, 2022
    1. Chang PM, Cheng CT, Wu RC, et al. : Nab-paclitaxel is effective against intrahepatic cholangiocarcinoma via disruption of desmoplastic stroma. Oncol Lett 16:566-572, 2018 - PMC - PubMed

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