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.
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