Results of the SWOG 1815 study failed to demonstrate a benefit with the addition of nab-paclitaxel to gemcitabine/cisplatin (GemCis) versus GemCis alone.
The standard of care for patients with advanced biliary tract cancer (BTC) has traditionally included gemcitabine/cisplatin (GemCis)-based regimens; however, the median overall survival (OS) is only about 12 months, emphasizing the need for a regimen that improves patient outcomes. Albumin-bound paclitaxel combined with GemCis (GAP) showed promising efficacy, with a median OS of 19.2 months in a single-arm phase 2 study. Results from SWOG 1815, a randomized, open-label, phase 3 trial comparing GAP with GemCis in patients with advanced BTC, were presented by Rachna Shroff, MD, MS, at the 2023 ASCO Gastrointestinal Cancers Symposium.
Patients with newly diagnosed, histologically proven, untreated advanced BTC were randomly assigned 2:1 to GAP or 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 Eastern Cooperative Oncology Group performance status of 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 addition of nab-paclitaxel to GemCis did not confer a survival benefit: 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 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.
Results from SWOG 1815, a randomized, open-label, phase 3 trial comparing GAP with GemCis in patients with advanced BTC, were presented by Rachna Shroff, MD, MS, at the 2023 ASCO Gastrointestinal Cancers Symposium.
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, respectively, but this improvement was not 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 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 produce a significant increase in median OS, and greater rates of TRAEs were seen with GAP, but there was no difference in discontinuation rates between the 2 groups. Although previous studies had promising outcomes, the results of SWOG 1815 failed to show a benefit with the addition of nab-paclitaxel to GemCis. Patients with locally advanced disease and GBC may benefit from GAP, but further research is needed to fully understand its therapeutic usefulness in these patient subgroups.
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. Abstract LBA490.
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