Pancreatic cancer is known as the "king of cancer", and the patient's prognosis is usually poor and is one of the main causes of cancer-related deaths worldwide. For resectable and junctional resectable pancreatic cancer, surgical resection remains one of the main strategies for

pancreatic cancer is known as the "king of cancer". Patient prognosis is usually poor and is one of the main causes of cancer-related deaths worldwide. For resectable and junctional resectable pancreatic cancer, surgical resection remains one of the main strategies for radical pancreatic cancer treatment. Previous studies have shown that adjuvant chemotherapy can improve survival benefits in patients with pancreatic cancer after surgery.

In terms of the choice of adjuvant chemotherapy, the PRODIGE 24/CCTG PA6 clinical trial showed that comparing the gemcitabine single-drug regimen, 5-FU+LV+irinotecan+oxaliplatin (mFOLFIRINOX) regimen significantly improved the median disease-free survival (median DFS, 21.6 months vs. 12.8 months, P0.0001) and median overall survival (median OS, 54.4 months vs. 35.0 months, P=0.003). Based on the results of this study, the mFOLFIRINOX regimen has become the preferred recommended solution for postoperative adjuvant treatment in patients with pancreatic cancer. Recently, the researchers released the final analysis results of the five-year trial on JAMA Oncology (IF: 33.006), edited and compiled by Yimaitong as follows.

Research Background

CONKO-001 and ESPAC-4 have shown that adjuvant chemotherapy is indispensable in improving survival benefits for patients with pancreatic cancer. The multicenter, randomized, phase III PRODIGE 24/CCTG PA6 clinical trial evaluated the application of mFOLFIRINOX regimen in patients with pancreatic cancer. Its 3-year analysis showed that at a median follow-up of 33.6 months, the DFS and OS performance of patients in mFOLFIRINOX group was significantly better than that of gemcitabine group, with 39.7% and 21.4% of patients' 3-year DFS, and 63.4% and 48.6% of 3-year OS, respectively. After a longer follow-up period, the investigators published the five-year analysis results of the study and analyzed the prognostic factors related to patients' OS.

study design

PRODIGE 24/CCTG PA6 study was conducted in 77 hospitals in France and Canada. The main inclusion criteria are pancreatic ductal cancer patients with ages 18-79, no metastatic disease, World Health Organization physical fitness score of 0-1 and good liver and kidney function. Patients need to complete R0 or R1 resection within 12 weeks before randomization. Patients were randomly (1:1) to receive adjuvant therapy for mFOLFIRINOX ( oxaliplatin 85 mg/m²; calcium folite 400 mg/m²; irinotecan 150-180 mg/m²; fluorouracil 2400 mg/m², q14d, 12 cycles) or adjuvant therapy for gemcitabine (1000 mg/m², d1, d8 and d15, q28d, 6 cycles) adjuvant therapy. The primary endpoint of the study was DFS, and the secondary endpoints included OS, metastasis-free survival, tumor-specific survival, and safety.

Study results

Figure 1 Patient randomization

Except for the mFOLFIRINOX group, the incidence rate of lymphovascular was higher (73.7% vs. 63.1%; P=0.02), there was no significant difference in the baseline characteristics of the patients between the two groups. (95%CI, 67.1-73.9), as of June 28, 2021, the median treatment time in the mFOLFIRINOX group and the gemcitabine group were 24.6 weeks and 24.0 weeks, respectively.

Survival Analysis

median follow-up 69.7 months later, 367 patients in the intention-to-treat (ITT) population showed disease progression. As shown in Figure 2, the median DFS in the mFOLFIRINOX group and the gemcitabine group were 21.4 months and 12.8 months (stratified HR=0.66; 95% C, 0.54-0.82; P<0.001),>

Figure 2 Patients' DFS performance

As shown in Figure 3, the median OS in the mFOLFIRINOX group and the gemcitabine group were 53.5 months and 35.5 months (stratified HR=0.68; 95%CI, 0.54-0.85; P<0.001),>

Figure 3 Patient OS performance

As shown in Figure 4, subgroup analysis did not find heterogeneity in the impact of treatment strategies on OS.

Figure 4 Analysis of the OS subgroup of patients with

also had significant differences in metastasis-free survival and tumor-specific survival. The median metastasis-free survival in mFOLFIRINOX group and gemcitabine group were 29.4 months and 17.7 months, respectively (stratified HR=0.64; 95% C, 0.52-0.80; P<0.001;>

Figure 5 Patient metastasis-free survival (left) and tumor-specific survival (right) Analysis of

prognosis factors analysis of

univariate analysis showed that prognostic factors that were significantly correlated with improvement in patients' OS include: the patient received mFOLFIRINOX treatment, the tumor location is in the body/tail of the pancreas, the tumor is well differentiated, the tumor is pT1-2, the tumor is pN0, the tumor stage is low (I, IIA and IIB), the lymph node positivity rate (0.0-0.20 or 0.20-0.40), R0 resection, and the vein is not resected.

As shown in Table 1, multivariate analysis showed that prognostic factors that were significantly correlated with improvement in patients' OS include: patients receiving mFOLFIRINOX treatment, hospital enrolled ≥10 patients, patients age <70>

Table 1 Multivariate analysis of OS prognostic factors

safety analysis

safety analysis is consistent with previous reports. Previous reports show that the incidence of grade 3-4 adverse events in mFOLFIRINOX group and gemcitabine group was 75.9% and 52.9%, respectively, of which the incidence of grade 4 adverse events was 12.2% and 12.0%, respectively (Table 2). The safety of mFOLFIRINOX regimen is lower than that of gemcitabine, but it is generally controllable, and no new safety signals are found after long-term follow-up.

Table 2 Safety analysis

Study conclusions

PRODIGE 24/CCTG PA6 trial final analysis showed that compared with gemcitabine regimen, mFOLFIRINOX adjuvant chemotherapy significantly prolonged DFS, OS, metastasis-free survival and tumor-specific survival in patients with pancreatic ductal cancer, and its safety is controllable. These results support the reliability of mFOLFIRINOX regimen as a standard adjuvant therapy in patients with pancreatic ductal cancer. In addition, the relevant factors affecting OS in patients with pancreatic ductal cancer were analyzed, providing assistance in determining tumor molecular characteristics and better choosing chemotherapy regimens.

Reference

. Conroy T, Castan F, Lopez A, et al. Five-Year Outcomes of FOLFIRINOX vs Gemcitabine as Adjuvant Therapy for Pancreatic Cancer: A Randomized Clinical Trial. JAMA Oncol. 2022;e223829. doi:10.1001/jamaoncol.2022.3829

. Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer. N Engl J Med. 2018;379(25):2395-2406. doi:10.1056/NEJMoa1809775

Review: You Shi

Type: You Shi

Execution: You Shi

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