Based on the results of the PRODIGE4/ACCORD11 and MPACT clinical trials, modified FOLFIRINOX (FFX) and Nab-paclitaxel plus Gemcitabine (AG) are frequently recommended as first-line treatment regimens for metastatic pancreatic cancer [4, 5]. Some retrospective or real-world studies have compared the effectiveness and safety of the two regimens [8,9,10, 12, 13]. However, since there is no clinical trial to directly compare the efficacy and safety of the two regimens, it is not clear which regimen is more effective. Additionally, the majority of these studies included not only metastatic pancreatic cancer (mPC) but also local advanced pancreatic cancer (LAPC) or borderline resectable tumors, resulting in a very heterogeneous study.
In this retrospective study, we aimed to compare the two standard first-line chemotherapy regimens only in Chinese patients with metastatic pancreatic cancer. Herein, our study showed no difference in terms of survival outcomes or tumor response between the patients treated with AG or FFX. Moreover, high PNI was a good prognostic factor for OS in the whole patients included in this study.
Previously, a randomized phase III trial showed that gemcitabine significantly improved disease-related symptoms and median OS compared with 5-fluorouracil alone in patients with locally advanced or metastatic pancreatic cancer [17]. Thus, gemcitabine monotherapy became the standard chemotherapy regimen for advanced pancreatic cancer since the 1990s. However, since more effective alternatives regimens have been developed, including AG or FFX, recent guidelines recommend the use of AG or FFX regimens for first-line treatment in locally advanced or metastatic pancreatic cancer based on the results of the MPACT trial and PRODIGE4/ACCORD11 trials [6, 7].
The present study showed that the overall survival of the AG group and FFX group as first-line therapy in metastatic pancreatic cancer were 9.00 months and 10.00 months respectively, consistent with their respective pivotal trials [4, 5]. The objective response rates (ORR) were 16.7% and 20.0% in the AG group and FFX group, respectively. No statistical difference was found between the two groups in terms of tumor responses. Immune checkpoint inhibitors (ICIs) based regimens are common second-line treatment options whether in AG or FFX group. Immunotherapy has reshaped the therapeutic pattern of many solid tumors, including lung cancer, gastric cancer, and melanoma [18,19,20,21]. Moreover, various clinical trials have also begun to explore the effect of immunotherapy on pancreatic cancer. An open-label, single-center, phase Ib/II clinical trial, which used toripalimab (anti-PD-1) plus AG as the first-line treatment for patients with locally advanced or metastatic pancreatic cancer, showed a favorable response and manageable toxicity [22]. Another randomized phase 2 trial conducted by researchers at the university of Pennsylvania and parker institute for cancer immunotherapy evaluated the efficacy of nivolumab (anti-PD-1) and/or sotigalimab (CD40 agonistic antibody) with AG in patients with first-line metastatic pancreatic cancer [23]. Thus, immunotherapy combined with chemotherapy may be a better treatment for advanced pancreatic cancer, which is worth further exploration and research.
The present study also found that PNI (prognostic nutritional index) was significantly related to the OS in metastatic pancreatic cancer. The patients in the high PNI group had a significantly longer median OS in this study. Nutritional status and immunity are closely related to the prognosis of patients with malignant tumors, according to many studies [24,25,26,27,28]. PNI is an easily accessible index that considers nutritional and immunologic factors. The preoperative nutritional index was first proposed by Buzby et al. [29] in 1980 and was initially used to assess preoperative nutritional status, surgical risk, and postoperative complications (PNI = 5 × total lymphocyte count (109/L) + serum albumin (g/L)). According to recent studies, PNI can be used to evaluate the prognosis of many cancers. Our study reported that low PNI was significantly associated with reduced survival in patients with metastatic pancreatic cancer. Additionally, studies have shown that nutritional interventions can reduce the risk of death among cancer patients. A phase III, randomized, controlled trial showed that early nutrition and psychological intervention could reduce the mortality risk of patients with advanced esophageal cancer by 32% [30]. A prospective, multicenter, randomized study showed that whole-course nutrition management is helpful to maintain the weight and nutritional status of esophageal cancer patients receiving concurrent radiotherapy and chemotherapy and improving their treatment tolerance and short-term prognosis [31]. Nutritional support may improve the prognosis of pancreatic cancer, which deserves further attention and research.
Non-systematic treatment of advanced and metastatic pancreatic cancer also has important clinical value. Due to the local expansion of pancreatic cancer, many pancreatic cancer patients may experience severe abdominal pain, which may seriously affect the quality of life of patients. Endoscopic ultrasonography guided-celiac plexus neurolysis (EUS-CPN) is an important option for the treatment of severe intractable pain in pancreatic cancer patients. Moreover, a retrospective study found that EUS-guided tumor ablation combined with CPN may be more effective and safe compared to standard EUS-CPN [32]. Meanwhile, radiotherapy is also widely used to relieve pain of pancreatic cancer [33].
This study has limitations. This study was a single-center retrospective study involving a relatively small number of patients with pancreatic cancer. The results need to be further confirmed by a large sample prospective study.
In conclusion, in this retrospective study, we aimed to compare the two standard first-line chemotherapy regimens only in Chinese patients with metastatic pancreatic cancer. Herein, our study showed no significant difference in terms of survival outcomes or tumor response between the patients treated with AG or FFX. Moreover, high PNI was a good prognostic factor for OS in the whole patients included in this study. Further studies are needed to prove which regimen works better in a wider range of situations. However, consistent with other research results, our study also suggested that the prognosis of patients with metastatic pancreatic cancer was very poor. Therefore, chemotherapy combined with targeted therapy or immunotherapy is worthy of further research as a more effective approach.