Hwang I, et al. ASCO GI 2018:354

Efficacy of nab-paclitaxel plus gemcitabine versus FOLFIRINOX as first-line chemotherapy for metastatic pancreatic cancer: Real-world experiences

Background

Gemcitabine plus nab-paclitaxel (GN) and FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) have led to significantly improved clinical outcomes when compared to gemcitabine alone in pivotal phase III trials in pancreatic cancer.1,2 However, there are no prospective head-to-head trials between GN and FOLFIRINOX in metastatic pancreatic cancer (MPC). Furthermore, there is a lack of real-world outcomes with both regimens. At ASCO GI 2018, Hwang and colleagues presented a retrospective efficacy assessment of outcomes of patients with MPC who were treated with either GN or FOLFIRINOX as the first-line chemotherapy in a real-world setting.3

Study design

  • The study analyzed 593 patients with advanced pancreatic cancer.
  • Of these, 77 patients were excluded due to recurrence of disease after curative resection, 206 due to locally advanced unresectable disease, and two due to having a histology of acinar cell carcinoma or neuroendocrine carcinomas.
  • A total of 308 patients were included in the final analysis.
  • The primary endpoints were progression-free survival (PFS) and overall survival (OS).
  • Secondary endpoints included overall response rate (ORR) and prognostic factors for PFS and OS.

Study design

Key findings

Baseline characteristics and disposition

  • A total of 149 patients from the NG arm and 159 from the FOLFIRINOX arm were included in the study.
  • The median age was 62 years (range: 32–82) in the GN arm and 60 years (range: 25–83) in the FOLFIRINOX arm.
  • Most of the patients in each arm were <65 years old (59.1% for GN and 69.2% for FOLFIRINOX).
  • The vast majority of patients in each arm had an Eastern Cooperative Oncology Group performance status of 0 or 1 (96.6% for GN and 99.4% for FOLFIRINOX).
  • The proportion of primary tumour site location was similar between the two arms.
  • Patients in the GN arm had a significantly higher proportion of lung and distant lymph node metastasis when compared with the FOLFIRINOX arm (20.1% vs. 8.2% and 41.6% vs. 26.4%, respectively).
  • The median duration of follow-up was 19.6 months in surviving patients (15.7 months in the GN arm vs. 35.3 months in the FOLFIRINOX arm).

Efficacy

  • The ORR and disease control rate did not significantly differ between the two arms. (Table 1)
  • The median PFS was numerically, but not significantly, higher with GN when compared with FOLFIRINOX (6.8 months vs. 5.0 months; p = 0.19). (Figure 1)
  • The median OS was significantly improved with GN when compared with FOLFIRINOX (11.4 months vs. 9.6 months; p = 0.002). (Figure 1)
  • The median PFS was significantly improved with GN versus FOLFIRINOX in patients ≥65 years (7.1 months vs. 5.0 months; p = 0.03), while only numerically higher with GN versus FOLFIRINOX in patients <65 years old (6.4 months vs. 5.4 months; p = 0.95).
  • The median PFS was significantly improved with GN versus FOLFIRINOX in patients with peritoneal metastasis (7.3 months vs. 5.0 months; p = 0.02), while only numerically higher with GN versus FOLFIRINOX in patients without peritoneal metastasis (5.8 months vs. 5.1 months; p = 0.91).
  • In patients who received subsequent second-line chemotherapy, both the median PFS and the median OS were significantly improved in patients who received first-line GN versus those who received first-line FOLFIRINOX. (Figure 2)
  • Elevated baseline CA19-9 (carbohydrate antigen 19-9) level and presence of liver metastasis were the only statistically significant prognostic factors for PFS. (Table 2)

Table 1. Objective response by regimen in patients with at least one measurable lesion

Figure 1. Progression-free survival and overall survival

Figure 2. Survival outcomes in patients with subsequent second-line chemotherapy

Table 2. Prognostic factors for PFS

Key conclusions

  • Efficacy outcomes for GN were comparable to those of FOLFIRINOX in the daily practice setting.
  • The significantly better OS with GN versus FOLFIRINOX may be attributed to the impact of subsequent second-line treatment.
  • Older patients (≥65 years) and those with peritoneal metastasis appeared to have more of a PFS benefit with GN versus FOLFIRINOX.
  • Liver metastasis and elevated baseline CA19-9 were significant prognostic factors for PFS.

References: 1. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364(19):1817–25. 2. Von Hoff DD, Ervin T, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Eng J Med 2013;369(18):1691–703. 3. Hwang I, Kang J, Yoo C, et al. Efficacy of nab-paclitaxel plus gemcitabine versus FOLFIRINOX as first line chemotherapy for metastatic pancreatic cancer: retrospective analysis. J Clin Oncol (ASCO GI Annual Meeting) 2018;36(Suppl): abstr 354.