Early Tumor Shrinkage and Depth of Response Evaluation in Metastatic Pancreatic Cancer Treated with First Line Chemotherapy: An Observational Retrospective Cohort Study.

Caterina Vivaldi,Monica Lencioni,Francescamaria Donati,Enrico Vasile,Piero Boraschi,Valentina Massa,Irene Pecora,Daniela Campani,Lorenzo Fornaro,Francesca Salani,Andrea Cacciato Insilla,Niccolò Napoli,Emanuele Kauffmann,Alfredo Falcone,Carla Cappelli,Giulia Pasquini,Silvia Catanese,Davide Caramella,Ugo Boggi

doi:10.3390/cancers11070939

Caterina Vivaldi, Monica Lencioni + Show 17 more

Open Access

https://doi.org/10.3390/cancers11070939

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Abstract

Early tumor shrinkage (ETS) and depth of response (DoR) predict favorable outcomes in metastatic colorectal cancer. We aim to evaluate their prognostic role in metastatic pancreatic cancer (PC) patients treated with first-line modified-FOLFIRINOX (FOLFOXIRI) or Gemcitabine + Nab-paclitaxel (GemNab). Hence, 138 patients were tested for ETS, defined as a ≥20% reduction in the sum of target lesions’ longest diameters (SLD) after 6–8 weeks from baseline, and DoR, i.e., the maximum percentage shrinkage in the SLD from baseline. Association of ETS and DoR with progression-free survival (PFS) and overall survival (OS) was assessed. ETS was reached in 49 patients (39.5% in the FOLFOXIRI, 29.8% in the GemNab group; p = 0.280). In the overall population, ETS was significantly associated with better PFS (8.0 vs. 4.8 months, p < 0.001) and OS (13.2 vs. 9.7 months, p = 0.001). Median DoR was −27.5% (−29.4% with FOLFOXIRI and −21.4% with GemNab, p = 0.016): DoR was significantly associated with better PFS (9.0 vs. 6.7 months, p < 0.001) and OS (14.3 vs. 11.1 months, p = 0.031). Multivariate analysis confirmed both ETS and DoR are independently associated with PFS and OS. In conclusion, our study added evidence on the role of ETS and DoR in the prediction of outcome of PC patients treated with first-line combination chemotherapy.

Highlights

Pancreatic cancer (PC) is the seventh leading cause of cancer-related death worldwide and is one of the most aggressive tumor types, with almost as many deaths (n = 432,000) as incident cases (n = 459,000) [1].Cancers 2019, 11, 939; doi:10.3390/cancers11070939 www.mdpi.com/journal/cancersConsidering all stages, from 2014 to 2018, the overall five-year survival rate increased from 6% to9%, but it still stands very poor [2]
Of 134 patients experiencing disease progression, 98 (73%) received a second-line chemotherapy treatment: of these, 65% were given combination regimens (GemNab, Folfox, Folfiri or Gemcitabine-Capecitabine doublets), while 35% were treated with monotherapies
The prognostic role of PS and liver involvement that emerged from our analysis had already been identified in ACCORD11/PRODIGE4 and MPACT trial analyses [5,17], strengthening the value of our results in an independent population treated at a single Institution

Summary

Introduction

Two important clinical trials recently changed the standard of care from single-agent gemcitabine to combination chemotherapy [5,6]. In the MPACT trial, Von Hoff et al demonstrated that the Gemcitabine plus Nab-paclitaxel (GemNab) regimen was associated with a longer OS in comparison to Gemcitabine monotherapy [5]. Since these two regimens (triplet or doublet combination) have been used as gold standard first-line treatments for patients with advanced PC in good clinical conditions [8]

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