Randomized phase II/III trial of gemcitabine plus nab-paclitaxel versus concurrent chemoradiotherapy with S-1 as neoadjuvant treatment for borderline resectable pancreatic cancer: GABARNANCE study.

Abstract

LBA4014 Background: No randomized controlled trials have compared systemic chemotherapy and chemoradiotherapy as neoadjuvant therapy for borderline resectable pancreatic cancer (BRPC). We attempted to determine which of the two could become established as standard neoadjuvant therapy for BRPC. Methods: This was an open-label, multicenter, randomized controlled phase II/III trial comparing two neoadjuvant treatments (UMIN-CTR 000026858): gemcitabine (GEM) plus nab-paclitaxel (nab-P) (group A, GEM 1000 mg/m2 IV + nab-P 125 mg/m2 IV on days 1, 8, and 15, 2 cycles) and concurrent chemoradiotherapy (50.4 Gy/28 fractions) with S-1 (80 mg/m2) on the irradiation days (group B). After the neoadjuvant therapy, patients (pts) underwent surgical resection if R0/R1 resection was judged as being possible, followed by postoperative adjuvant S-1 therapy for 6 months. The key eligibility criteria included patients aged 20 to 79 years with histologically proven adeno(squamous)carcinoma, centrally confirmed BRPC, PS 0-1, and no prior treatment for BRPC. The primary endpoint of the phase III part was overall survival (OS). A total of 110 pts (65 events) was required to detect a 17% difference in the 2-year OS [hazard ratio (HR) of 0.70] with a two-sided alpha level of 10% and power of 70%. Results: A total of 112 pts were randomly assigned to the trial treatments between June 2017 and December 2022 (group A/B: 56/56 pts). The median OS was 23.1 months in group A and 31.5 months in group B. No statistically significant difference in the OS was observed between the two arms (HR 0.758, 95% CI: 0.472-1.219, p = 0.2518), but a large late separation of the Kaplan-Meier curves was observed after 18 months. The difference in the 2-year OS between the groups was 14.6% (group A: 48.2%, group B: 62.8%); the separation continued until the end of the observed survival curves. A similar late separation in the PFS was seen after around 12 months, but the difference in the PFS was not statistically significant (median PFS: Group A, 12.6 months, Group B, 11.1 months; HR 0.805; 95% CI: 0.535-1.212; p = 0.2565). The R0 resection rate did not differ between the two groups (group A, 60.7%; group B, 57.1%). The tumor response rate was higher in Group A (group A, 16.1%; group B, 8.9%), but the pathological response rate was higher in group B (group A, 14.3%; group B, 30.4%). Neutropenia and thrombocytopenia were observed more frequently in group A, while anorexia was observed more frequently in group B. Both treatments were well-tolerated. Conclusions: A delayed survival advantage, in terms of both the OS and PFS, of concurrent chemoradiotherapy with S-1 was observed, without any additional toxicity burden. An updated analysis with longer-term efficacy/toxicity data is planned to verify the advantage of neoadjuvant chemoradiotherapy. Clinical trial information: UMIN-CTR 000026858.