GABARNANCE OS, PFS Results: Gemcitabine, Nab-Paclitaxel With Concurrent Chemoradiotherapy for Pancreatic Cancer

New results from the randomized, phase 2/3 GABARNANCE trial were presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology Annual Meeting by Masafumi Ikeda, MD.

GABARNANCE compared the use of gemcitabine plus nab-paclitaxel with concurrent chemoradiotherapy plus S-1 to determine which can be established as a standard neoadjuvant treatment for patients with borderline resectable pancreatic cancer (BRPC).

S-1 is a novel oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine used for the treatment of multiple forms of cancer, including gastric and pancreatic cancers.

Between June 2017 and December 2022, the open-label, multicenter trial assigned 112 patients to receive intravenous (IV) gemcitabine 1000 mg/m² plus IV nab-paclitaxel 125 mg/m² on days 1, 8, and 15 for 2 treatment cycles (group A, 56 patients), with concurrent chemoradiotherapy (50.4 Gy/28 fractions) plus S-1 80 mg/m² on the irradiation days (group B, 56 patients).

After undergoing neoadjuvant therapy, patients underwent surgical resection, if it was determined to be possible, followed by postoperative treatment with S-1 therapy for 6 months. The primary end point of phase 3 was overall survival (OS). A total of 110 patients (65 events) was required to detect a 17% difference in the 2-year OS (hazard ratio [HR], 0.70) with a 2-sided alpha level of 10% and power of 70%.

The median OS in groups A and B was 23.1 and 31.5 months, respectively. While no statistically significant difference in OS rates was observed between the 2 arms (HR, 0.758; 95% CI, 0.472-1.219; P=.2518), a large late separation of the Kaplan-Meier curves was seen after 18 months.

The difference in 2-year OS between the groups was 14.6% (group A, 48.2%; group B, 62.8%), and the separation continued until the end of the observed survival curves. A similar late separation in progression-free survival (PFS) was also seen after around 12 months, but this difference was not statistically significant (median PFS in group A, 12.6 months; median PFS in group B, 11.1 months; HR, 0.805; 95% CI, 0.535-1.212; P=.2565).

The resection rate did not differ between the 2 groups (group A, 60.7%; group B, 57.1%). The tumor response rate was higher in group A (16.1%) than in group B (8.9%), but the pathological response rate was higher in group B (30.4%) than in group A (14.3%). Neutropenia and thrombocytopenia occurred more in group A, while treatment-related anorexia was observed more frequently in group B. Both treatments were well tolerated.

In both OS and PFS, there was a delayed survival advantage of concurrent chemoradiotherapy with S-1, without any additional toxicity. An updated analysis featuring longer-term efficacy and toxicity data is planned for the future to verify the advantage of neoadjuvant chemoradiotherapy.