Adding nab-paclitaxel to combination treatment with gemcitabine and cisplatin does not improve outcomes for patients with newly diagnosed, advanced biliary tract cancers, a phase 3 trial suggests.
Nab-paclitaxel did not improve the response rate, progression-free survival (PFS), or overall survival (OS) in this trial. These findings were presented at the 2023 ASCO Gastrointestinal Cancers Symposium by Rachna T. Shroff, MD, of the University of Arizona Cancer Center in Tucson.
The phase 3 SWOG 1815 trial (ClinicalTrials.gov Identifier: NCT03768414) enrolled patients with newly diagnosed, advanced cholangiocarcinoma or gallbladder cancer. They were randomly assigned to receive nab-paclitaxel, gemcitabine, and cisplatin (n=294) or gemcitabine and cisplatin (n=147).
Continue Reading
The median age at baseline was 63.2 years in the triplet arm and 63.9 years in the control arm. Most patients had metastatic disease (74% and 72%, respectively). They had extrahepatic (17% and 16%, respectively), intrahepatic (67% in both arms), and gallbladder tumors (16% in both arms).
Patients in the triplet arm received gemcitabine at 800 mg/m2, cisplatin at 25 mg/m2, and nab-paclitaxel at 100 mg/m2 on days 1 and 8 of a 21-day cycle. Patients in the control arm received gemcitabine at 1000 mg/m2 and cisplatin at 25 mg/m2 on days 1 and 8. In both arms, patients were treated until disease progression or intolerance.
The overall response rate was 31% in the triplet arm and 22% in the control arm. Disease control rates were 77% and 69%, respectively. Neither difference was significant.
The median OS was 14.0 months in the triplet arm and 12.7 months in the control arm (P =.65). The median PFS was 8.2 months in the triplet arm and 6.4 months in the control arm (P =.43).
Analyses of OS and PFS by disease site did not reveal significant differences between the treatment arms. However, among patients with locally advanced disease, the median OS and PFS were significantly longer with the triplet vs the doublet. The median OS was 19.2 months and 13.7 months, respectively (P =.01). The median PFS was 9.3 months and 7.6 months, respectively (P =.04).
Common grade 3-4 treatment-related adverse events (in the triplet and control arms, respectively) were anemia (33% and 22%), neutropenia (37% and 28%), thrombocytopenia (20% and 15%), and leukopenia (25% and 10%). Treatment discontinuation rates did not differ significantly between the arms.
Fatal adverse events were reported in 7 patients in the triplet arm. Three patients died of sepsis, and 1 each died of cardiac arrest, thromboembolism, upper gastrointestinal hemorrhage, and superior vena cava syndrome.
“This study did not meet its primary endpoint, but I still think it had a positive impact in the space of biliary tract cancers,” Dr Shroff said. “It is the first randomized phase 3 trial in this disease, and it proved that we can do a randomized phase 3 trial in a rare tumor like biliary tract cancers.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Shroff RT, Guthrie KA, Scott AJ, et al. SWOG 1815: A phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. ASCO GI 2023. January 19-21, 2023. Abstract LBA490.
