Multi-agent neoadjuvant chemotherapy improves survival in early-stage pancreatic cancer: A National Cancer Database analysis

Purpose: To compare overall survival (OS) in patients who underwent surgery for early-stage pancreatic adenocarcinoma (rPca) based on sequence (NAT, neoadjuvant therapy and/or AT, adjuvant therapy) and type (SA, single-agent or MA, multi-agent) of chemotherapy received. Methods: Using the National Cancer Database, patients with clinical stage I/II rPca diagnosed between 2010 and 2014 were identified and five comparison matches (1: NAT vs. upfront resection (UR); 2: multi-agent neoadjuvant (MA NAT) vs. single-agent adjuvant therapy (SA AT), single-agent neoadjuvant therapy (SA NAT), multi-agent adjuvant therapy (MA AT); 3: MA NAT vs. MA AT; 4: NAT thorn AT vs NAT; 5: NAT thorn AT vs AT) were constructed using minimum distance matching strategy. Median OS (mOS) was analysed using KaplanMeier method, log-rank test and Cox proportional hazard model. Results: A total of 18,470 patients with stage I/II rPca were eligible for analysis. NAT showed a 5 month (mo.) improved OS compared with UR (3271 patients/group, 28.1 vs 23.2 mo. P < 0.0001 hazard ratio [HR]: 0.79). MA-NAT was shown to be superior to other chemotherapy approaches SA AT, SA NAT, and MA AT (1349 patients/group: 30 vs. 25.9 mo., P = 0.0001 [HR: 0.82]). MA NAT showed a survival advantage over MA-AT (1349 patients/group, 30 vs 26.1 mo., P = 0.0008 [HR: 0.86]). The combination of NAT and AT showed a better outcome when compared with NAT alone ( 1128 patients/group, 31.6 vs 27.4 mo., P = 0.0011 [HR: 0.81]) or AT alone (1128 patients/group, 31.6 vs. 25.2 mo., P < 0.0001 [HR: 0.76]). Conclusions: In patients with stage I/II rPca, MA NAT showed improved mOS compared to UR and all other chemotherapy sequences except both NAT plus AT. These findings support the use of MA NAT in stage I/II rPca patients and warrant prospective trials evaluating MA NAT and post-resection maintenance therapies. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

In patients with stage I/II pancreatic adenocarcinoma, multi-agent neoadjuvant therapy (MA NAT) showed improved median overall survival (mOS) compared to upfront resection and all other chemotherapy sequences, except the combination of neoadjuvant and adjuvant therapy. This suggests the potential benefit of using multi-agent neoadjuvant therapy in these patients.