Impact of response to gemcitabine-based neoadjuvant therapy on the outcomes of gemcitabine plus nab-paclitaxel after recurrence in pancreatic cancer.

Abstract

675 Background: Gemcitabine (GEM)-based neoadjuvant chemoradiotherapy is administered to facilitate curative resection in pancreatic ductal adenocarcinoma (PDAC). For recurrent PDAC after resection, gemcitabine plus nab-paclitaxel (GnP) therapy is often selected as first-line systemic therapy, resulting in repeated exposure to GEM-containing regimens. However, it is unclear how the response to prior GEM-based neoadjuvant therapy influences the efficacy of GnP for recurrence. This study aimed to evaluate whether tumor regression during neoadjuvant therapy correlates with GnP treatment outcomes in patients with recurrent PDAC. Methods: We retrospectively reviewed 51 patients with resectable and borderline resectable PDAC who received neoadjuvant GEM-based chemoradiotherapy, followed by curative-intent resection between April 2014 and March 2023, and who received subsequent first-line chemotherapy with GnP for recurrence. Patients were classified into a "high-regression group” (≥30% tumor reduction during neoadjuvant therapy, n = 32) or a "low-regression group” ( < 30% reduction, n = 19) based on the response to the neoadjuvant chemoradiotherapy. Overall survival (OS) and progression free survival (PFS) was measured from the treatment initiation for recurrent PDAC. Results: At the time of initial diagnosis, the median age was 63 years (range, 46-78); 27 patients were men. 27 patients were resectable PDAC. All patients underwent neoadjuvant chemoradiation therapy, and chemotherapy regimens in 36 of these cases were GnP. After the neoadjuvant chemoradiotherapy, 30 patients underwent pancreaticoduodenectomy, 20 underwent distal pancreatectomy, and one underwent total pancreatectomy. R0 resection was achieved in 50 patients. After the surgery, adjuvant chemotherapy based on S-1 was administered to 45 patients. The most common sites of recurrence were the lung and liver in 17 patients each, followed by local recurrence in 16 patients (including duplicates). The median follow-up after initiation of GnP therapy was 17.9 months. Patients in the high-regression group demonstrated a significantly longer median PFS compared to the low-regression group (11.8 months vs. 5.8 months, p = 0.010). Similarly, the objective response rate (ORR) was significantly higher in the high-regression group (43.8% vs. 10.5%, p = 0.015). However, there was no significant difference in median OS between the two groups (19.9 months vs. 18.6 months, respectively; p = 0.784). Conclusions: Patients with greater tumor regression during GEM-based neoadjuvant chemoradiotherapy had better PFS and ORR to GnP therapy after recurrence. These findings may suggest the importance of tumor response to neoadjuvant therapy as a potential predictor of chemosensitivity and support its use as a guide for subsequent treatment strategies for recurrent PDAC.