FOLFIRINOX or gemcitabine/nab-paclitaxel in advanced pancreatic adenocarcinoma: A novel validated prognostic score to facilitate treatment decision-making in real-world

Norbert Marschner, Susanna Hegewisch-Becker, Marcel Reiser, Eyck von der Heyde, Mathias Bertram, Stephan H Hollerbach, Stephan Kreher, Thomas Wolf, Adrian Binninger, Marco Chiabudini, Anja Kaiser-Osterhues, Martina Jänicke, TPK-Group (Tumour Registry Pancreatic Cancer), Norbert Marschner, Susanna Hegewisch-Becker, Marcel Reiser, Eyck von der Heyde, Mathias Bertram, Stephan H Hollerbach, Stephan Kreher, Thomas Wolf, Adrian Binninger, Marco Chiabudini, Anja Kaiser-Osterhues, Martina Jänicke, TPK-Group (Tumour Registry Pancreatic Cancer)

Abstract

There is no prospective, randomised head-to-head trial comparing first-line FOLFIRINOX and gemcitabine/nab-paclitaxel in advanced pancreatic cancer. We assess real-world effectiveness and quality of life (QoL) of both regimens using a new prognostic score. This analysis includes 1540 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer separated into learning (n = 1027) and validation sample (n = 513). The Pancreatic Cancer Score (PCS) was developed using multivariate Cox regression. We compared overall survival (OS) and time to deterioration (TTD) for longitudinal QoL between first-line FOLFIRINOX (n = 407) and gemcitabine/nab-paclitaxel (n = 655) according to patients' prognostic risk, after inverse probability of treatment weighting (IPTW) by propensity score analysis. The PCS includes nine independent prognostic factors for survival: female sex, BMI ≥24/unknown, ECOG performance status ≥1, Charlson comorbidity index ≥1, tumour staging IV/unknown at primary diagnosis, liver metastases, bilirubin >1.5× upper limit of normal (ULN), leukocytes >ULN and neutrophil-to-lymphocyte ratio ≥4. Median OS of the validation sample was 11.4 (95% confidence interval [CI]: 10.4-14.4), 8.5 (95% CI: 6.8-9.6) and 5.9 months (95% CI: 4.0-7.4) for favourable- (0-3 risk factors), intermediate- (4-5 factors) and poor-risk group (6-9 factors), respectively. After IPTW, only poor-risk patients had significantly longer median OS and TTD of overall QoL with FOLFIRINOX (OS: 6.9 months, 95% CI: 3.9-13.3; TTD: 10.6 months, 95% CI: 2.0-14.1) vs gemcitabine/nab-paclitaxel (OS: 4.0 months, 95% CI: 2.8-4.8; TTD: 4.1 months, 95% CI: 2.4-4.5). Our novel PCS may facilitate treatment decisions in clinical routine of advanced pancreatic cancer, since only poor-risk, but not favourable-risk patients, seem to benefit from intensified treatment with FOLFIRINOX.

Trial registration: ClinicalTrials.gov NCT02089269.

Keywords: FOLFIRINOX; cohort studies; gemcitabine/nab-paclitaxel; pancreatic carcinoma; prognostic score.

Conflict of interest statement

Marcel Reiser, Eyck von der Heyde, Mathias Bertram, Stephan H. Hollerbach, Stephan Kreher, Thomas Wolf, Adrian Binninger, Marco Chiabudini, Anja Kaiser‐Osterhues and Martina Jänicke declare no conflict of interest concerning the topic of this publication. Outside of the published work, the institutions of Susanna Hegewisch‐Becker, Marcel Reiser, Eyck von der Heyde, Mathias Bertram, Stephan H. Hollerbach, Stephan Kreher and Thomas Wolf received remuneration for the documentation of patient data. Norbert Marschner reported receiving honoraria for talks and attendance of conferences from Celgene and Servier; he is Chief executive officer and shareholder of iOMEDICO AG. Susanna Hegewisch‐Becker reported a consulting or advisory role for Servier.

© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Figures

FIGURE 1
FIGURE 1
Flow chart. Patient flow chart of all patients with advanced pancreatic cancer included in this analysis, starting from the total number of patients recruited into the TPK registry from February 2014 until June 2020. The study cohort consists of all patients with advanced pancreatic cancer and palliative first‐line treatment who had not received any prior (neo)adjuvant systemic treatment (n = 1540, prognosis score population) including 1062 patients treated with FOLFIRINOX or GEMNAB in first line (IPTW population). doc., documented; GEMNAB, gemcitabine plus nab‐paclitaxel; inclus., inclusion
FIGURE 2
FIGURE 2
Overall survival of learning and validation sample. (A) OS of learning (n = 1027) and (B) validation sample (n = 513) by risk groups according to the PCS. CI, confidence interval; OS, overall survival; PCS, Pancreatic Cancer Score
FIGURE 3
FIGURE 3
Overall survival after IPTW. OS after IPTW in patients receiving first‐line treatment with either FOLFIRINOX or GEMNAB independent of prognostic risk (A), by favourable risk (B), intermediate risk (C) and poor risk (D) according to the PCS. Numbers at risk refer to the sum of weights of the respective patients at risk for a given time point. Due to rounding, the weights of the three risk groups do not exactly add up to the sum of weights calculated for the FOLFIRINOX‐ and the GEMNAB‐IPTW cohorts, as shown in (A). P‐values were calculated with the log‐rank test. CI, confidence interval; GEMNAB, gemcitabine plus nab‐paclitaxel; OS, overall survival; PCS, Pancreatic Cancer Score
FIGURE 4
FIGURE 4
Time to deterioration of overall quality of life after IPTW. TTD of overall QoL (global health status) after IPTW in patients receiving first‐line treatment with either FOLFIRINOX or GEMNAB independent of prognostic risk (A), by favourable risk (B), intermediate risk (C) and poor risk (D) according to the PCS. Numbers at risk refer to the sum of weights of the respective patients at risk for a given time point. Due to rounding, the weights of the three risk groups do not exactly add up to the sum of weights calculated for the FOLFIRINOX‐ and the GEMNAB‐IPTW cohorts, as shown in (A). P‐values were calculated with the log‐rank test. CI, confidence interval; GEMNAB, gemcitabine plus nab‐paclitaxel; PCS, Pancreatic Cancer Score; QoL, quality of life; TTD, time to deterioration

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