SWOG S1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers Journal Article
| Authors: | Shroff, R. T.; King, G.; Colby, S.; Scott, A. J.; Borad, M. J.; Goff, L.; Matin, K.; Mahipal, A.; Kalyan, A.; Javle, M. M.; El Dika, I.; Tan, B.; Cheema, P.; Patel, A.; Iyer, R.; Kelley, R. K.; Thumar, J.; El-Khoueiry, A.; Guthrie, K. A.; Chiorean, E. G.; Hochster, H.; Philip, P. A. |
| Article Title: | SWOG S1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers |
| Abstract: | PURPOSESWOG 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).METHODSPatients 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).RESULTSAmong 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).CONCLUSIONThe 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. © American Society of Clinical Oncology. |
| Keywords: | adult; controlled study; treatment response; aged; aged, 80 and over; middle aged; survival analysis; major clinical study; overall survival; clinical trial; constipation; fatigue; mortality; paresthesia; hepatitis; cisplatin; advanced cancer; ascites; diarrhea; drug safety; hypertension; side effect; gemcitabine; paclitaxel; comparative study; antineoplastic agent; cancer diagnosis; anorexia; progression free survival; multiple cycle treatment; neutrophil count; pain; sensory neuropathy; anemia; bleeding; esophagitis; mucosa inflammation; nausea; randomized controlled trial; thrombocytopenia; vomiting; antineoplastic combined chemotherapy protocols; dehydration; myalgia; delirium; ca 19-9 antigen; creatinine; pathology; abdominal pain; arthralgia; backache; dizziness; dyspnea; febrile neutropenia; fever; hyperglycemia; hypomagnesemia; chronic disease; alanine aminotransferase; alkaline phosphatase; bilirubin; acute kidney failure; dysphagia; hyperkalemia; hypoalbuminemia; hypokalemia; hyponatremia; hypotension; albumin; albumins; heart failure; multicenter study; thromboembolism; urinary tract infection; muscle weakness; peripheral edema; sepsis; colitis; pleura effusion; open study; intrahepatic cholangiocarcinoma; bile duct carcinoma; cholangiocarcinoma; flu like syndrome; seizure; headache; phase 3 clinical trial; memory disorder; drug therapy; gallbladder carcinoma; gallbladder neoplasms; lung infection; portal vein thrombosis; deoxycytidine; catheter infection; epistaxis; gastrointestinal disease; hepatobiliary disease; atrial fibrillation; bilirubin blood level; ataxia; cholecystitis; adverse drug reaction; hearing impairment; biliary tract cancer; supraventricular tachycardia; biliary tract neoplasms; lymphocyte count; heart arrest; skin infection; multiple organ failure; respiratory tract disease; biliary tract tumor; hypocalcemia; respiratory failure; motor neuropathy; enterocolitis; superior cava vein syndrome; progression-free survival; lymphatic system disease; wheezing; gallbladder tumor; typhlitis; exploratory research; peritonitis; thrush; gamma glutamyl hydrolase; vascular access; 130-nm albumin-bound paclitaxel; extrahepatic cholangiocarcinoma; infective endocarditis; Common Terminology Criteria for Adverse Events; stomach hemorrhage; upper gastrointestinal bleeding; faintness; infusion related reaction; peripheral motor neuropathy; very elderly; null hypothesis; humans; human; male; female; article; infestation; lower limb; peripheral sensory neuropathy; triplet chemotherapy; doxecitine; generalized muscle weakness |
| Journal Title: | Journal of Clinical Oncology |
| Volume: | 43 |
| Issue: | 5 |
| ISSN: | 0732-183X |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2025-02-10 |
| Start Page: | 536 |
| End Page: | 544 |
| Language: | English |
| DOI: | 10.1200/jco-24-01383 |
| PUBMED: | 39671534 |
| PROVIDER: | scopus |
| PMCID: | PMC11798714 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
