Results from SWOG 1815: GemCis and Nab-Paclitaxel versus GemCis in Advanced BTC

March 2023, Vol 4, No 1 — April 4, 2023

Dr. Rachna Shroff

Although regimens including gemcitabine/cisplatin (GemCis) have been standard of care for patients with advanced biliary tract cancers (BTCs), the median overall survival (OS) is roughly 12 months, warranting the need for a regimen that improves patient outcomes. In a single-arm, phase 2 study, albumin-bound paclitaxel added to GemCis (GAP) demonstrated promising efficacy with a median OS of 19.2 months. At the 2023 ASCO Gastrointestinal Cancers Symposium, Dr Rachna Shroff presented results from SWOG 1815, a randomized, open-label, phase 3 trial comparing GAP to GemCis in patients with advanced BTC.

Patients had newly diagnosed, histologically proven, untreated advanced BTC and were randomly assigned 2:1 to GAP versus GemCis. Patients were restaged every 3 cycles until disease progression. The primary end point was OS, with a target hazard ratio of 0.7 with 90% power and a 1-sided alpha of 0.025. Secondary end points included overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), and CA 19-9 changes. Randomization was stratified by intrahepatic cholangiocarcinoma (iCCA) versus gallbladder adenocarcinoma (GBC) versus extrahepatic CCA (eCCA), locally advanced versus metastatic, and ECOG performance status 0 versus 1.

A total of 441 eligible patients were randomly assigned, 294 to GAP and 147 to GemCis. In all, 67% of patients had iCCA, 16% had GBC, and 17% had eCCA. A total of 73% of patients had metastases versus locally advanced disease. The median OS was 14 months with GAP versus 12.7 months with GemCis (P = .65). The median PFS for GAP versus GemCis was 8.2 months versus 6.4 months (P = .43). No statistically significant differences were seen between GAP and GemCis by disease site, but a trend was evident toward better survival with GAP in patients with GBC, with a median OS of 17 months with GAP versus 9.3 months with GemCis.

In an exploratory subset analysis of patients with locally advanced disease, the median OS was 19.2 months with GAP versus 13.7 months with GemCis (P = .01). A similar trend in PFS was seen in patients with locally advanced disease, with a median PFS of 9.3 months with GAP versus 7.6 months with GemCis (P = .04). The ORR was 31% with GAP versus 22% with GemCis, and the DCR was 77% with GAP versus 69% with GemCis. The ORR in patients with GBC was 44% with GAP versus 22% with GemCis; in addition, a slight improvement was seen in patients with eCCA, with an ORR of 34% versus 21% with GAP versus GemCis, but this improvement was not statistically significant. The ORR in patients with locally advanced disease was 28% with GAP versus 21% with GemCis, and 32% versus 23% in patients with metastatic disease, but this too was not statistically significant. The most common grade 3-4 treatment-related adverse events (TRAEs) with GAP included anemia (33%), neutropenia (37%), leukopenia (25%), and thrombocytopenia (20%). The most common grade 3-4 TRAEs with GemCis were anemia (22%), neutropenia (28%), thrombocytopenia (15%), and leukopenia (10%). Other TRAEs included alopecia, alanine transaminase increase, anorexia, constipation, edema, hypomagnesemia, nausea, and vomiting.

SWOG 1815 did not result in a statistically significant improvement in median OS with GAP versus GemCis, and higher rates of TRAEs occurred with GAP but no difference in discontinuation rates between the 2 arms. GAP may be beneficial in patients with locally advanced disease and GBC; however, further analysis is warranted to understand the clinical utility in these subsets of patients.

Source: 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. Oral abstract presented at: ASCO Gastrointestinal Cancers Symposium, January 19-21, 2023; San Francisco, CA.

Related Items

Characterization of Long-Term Survivors in TOPAZ-1
March 2023, Vol 4, No 1
Researchers examined the characteristics, outcomes, and genomic profiles of patients with advanced biliary tract cancer who were treated with durvalumab plus gemcitabine/cisplatin and experienced long-term survival.
MDM2-p53 Antagonist BI 907828 Demonstrated Promising Activity in Patients with Advanced BTC
March 2023, Vol 4, No 1
The novel MDM2-p53 antagonist BI 907828 is being investigated as a first-line treatment in patients with advanced biliary tract cancer.
Treatment and Survival Outcomes with Systemic Therapy for Patients with BTC with IDH1 Mutations: A Retrospective Study
March 2023, Vol 4, No 1
Long-term outcomes were evaluated in patients with IDH1-mutated biliary tract cancer who were treated with systemic therapy.
Phase 2 Study of CTX-009 plus Paclitaxel in Patients with Advanced BTC
March 2023, Vol 4, No 1
CTX-009 plus paclitaxel showed promising efficacy as second- or third-line treatment in patients with advanced biliary tract cancer.
Gunagratinib in Patients with Previously Treated Advanced CCA Harboring FGFR2 Fusions or Rearrangements
March 2023, Vol 4, No 1
Gunagratinib showed promising efficacy as a second-generation FGFR inhibitor and demonstrated potential to treat multiple FGFR pathway abnormalities.
JCOG1202 Subgroup Analysis: Risk Factors for Early Relapse in Patients Undergoing Curative Resection
March 2023, Vol 4, No 1
A study of patients with resected biliary tract cancer (BTC) found that postoperative CA 19-9 level, tumor differentiation, lymph node metastases, and residual tumor significantly impact early relapse in patients with curatively resected BTC. Similar risk factors were also found in patients receiving adjuvant S-1.
Impact of Gene Expression in 5-FU Metabolic Pathways on Outcomes in Patients Enrolled in JCOG1202
March 2023, Vol 4, No 1
Results from a study evaluating the impact of 5-FU metabolic pathway enzyme expression on outcomes of patients with curatively resected biliary tract cancer showed that relapse-free survival was improved in patients with certain enzymes who received adjuvant S-1.
Atezolizumab with or without Bevacizumab in Combination with GemCis in Advanced BTC: Results from IMbrave 151
March 2023, Vol 4, No 1
Researchers assessed whether VEGF blockade plus chemotherapy with gemcitabine/cisplatin can enhance responses to PD-L1 inhibition by promoting an immune-permissive tumor microenvironment in patients with advanced biliary tract cancer.
Nab-Paclitaxel plus Sintilimab as Second-Line Treatment for Advanced BTC
March 2023, Vol 4, No 1
The safety and efficacy of second-line nab-paclitaxel combined with the anti-PD-1 antibody sintilimab was studied in patients with advanced biliary tract cancer.
ICIs as Salvage Therapy for BTCs with KRAS Mutation
March 2023, Vol 4, No 1
Results are presented from a retrospective analysis of molecular profiles in patients with biliary tract cancers to assess the efficacy of immune checkpoint inhibitors according to KRAS mutation.

Subscribe Today!

To sign up for our newsletter or print publications, please enter your contact information below.

I'd like to receive: