Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma

Abstract

Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM. Materials and Methods Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors. Results Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy. Conclusion 2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.

Real World Evidence on Second-Line Palliative Chemotherapy in Advanced Pancreatic Cancer

“…Regression analyses were performed in order to define potentially prognostic baseline parameters. In line with previous reports ( 19 , 20 , 22 – 24 ), no prognostic impact of age or gender was evident in terms of mOS2 and TTF2. Neither was tumor burden (locally advanced vs. metastatic disease) a statistically significant prognostic parameter.…”

“…Estimated mTTF2 was 2.0 and 1.4 months in patients with ECOG performance status of ≤1 and >1, respectively. These results, together with other publications (16,(21)(22)(23), imply that ECOG performance status >1 predicts a poor outcome with short time to treatment failure and progression, and raise uncertainty whether second-line chemotherapy has any role in this type of patients.…”

“…These numbers are almost identical to the mOS2 of 5.2 months observed in the present patient cohort. Two other observational studies included patients with all forms of second-line regimens, but first-line treatment was restricted to gemcitabine based regimens only (21,22). These publications report mOS2 measures ranging from 4.5 to 7.3 months.…”

Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG)

“… 3 Gemcitabine monotherapy remains a valid treatment option for patients with poor performance status. 4 Previous studies have assessed the role of 5-fluorouracil (5-FU)-based therapies in patients who progressed following gemcitabine-based therapy 5 , 6 , 7 , 8 , 9 ; however, there is no clear consensus on the best second-line treatment for patients with metastatic pancreatic cancer (MPC) after progression following gemcitabine-based chemotherapy.…”

FOLFIRINOX after first-line gemcitabine-based chemotherapy in advanced pancreatic cancer: a retrospective comparison with FOLFOX and FOLFIRI schedules

“…A recent retrospective study has compared fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) and fluoropyrimidine monotherapy (S-1) in this setting for Korean patients, although it failed to detect significant differences in PFS and OS. 22 Therefore, to the best of our knowledge, ours is the first study to compare three second-line poly-chemotherapy regimens for advanced PDAC that progressed during first-line gemcitabine-based treatment. Thus, prospective trials are needed to investigate the role of second-line FOLFIRINOX treatment after failure of first-line gemcitabine-based treatment, and especially after failure of gemcitabine plus nab-paclitaxel, which is currently the standard of care in most countries.…”