Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial)

Mustafa Suker; Joost J Nuyttens; Ferry A L M Eskens; Brigitte C M Haberkorn; Peter-Paul L O Coene; Erwin van der Harst; Bert A Bonsing; Alexander L Vahrmeijer; J Sven D Mieog; Rutger Jan Swijnenburg; Daphne Roos; B Groot Koerkamp; Casper H J van Eijck

doi:10.1016/j.eclinm.2019.10.013

Efficacy and feasibility of stereotactic radiotherapy after folfirinox in patients with locally advanced pancreatic cancer (LAPC-1 trial)

EClinicalMedicine. 2019 Nov 19:17:100200. doi: 10.1016/j.eclinm.2019.10.013. eCollection 2019 Dec.

Affiliations

¹ Department of Surgery, Erasmus University Medical Center, Rotterdam, Netherlands.
² Department of Radiotherapy, Erasmus University Medical Center, Rotterdam, Netherlands.
³ Department of Oncology, Erasmus University Medical Center, Rotterdam, Netherlands.
⁴ Department of Oncology, Maasstad Hospital, Rotterdam, Netherlands.
⁵ Department of Surgery, Maasstad Hospital, Rotterdam, Netherlands.
⁶ Department of Surgery, Leiden University Medical Center, Leiden, Netherlands.
⁷ Department of Surgery, Reinier de Graaf Group, Delft, Netherlands.

Abstract

Background: We conducted a multicentre phase II trial to investigate feasibility and antitumor activity of sequential FOLFIRINOX and Stereotactic Body Radiotherapy (SBRT) in patients with locally advanced pancreatic cancer (LAPC), (LAPC-1 trial).

Methods: Patients with biopsy-proven LAPC treated in four hospitals in the Netherlands between December 2014 and June 2017. Patients received 8 cycles of FOLFIRINOX followed by SBRT (5 fractions/8 Gy) if no tumour progression after the FOLFIRINOX treatment was observed. Primary outcome was 1-year overall survival (OS). Secondary outcomes were median OS, 1-year progression-free survival (PFS), treatment-related toxicity, and resection rate. The study is registered with ClinicalTrials.gov, NCT02292745, and is completed.

Findings: Fifty patients were included. Nineteen (38%) patients did not receive all 8 cycles of FOLFIRINOX, due to toxicity (n = 12), disease progression (n = 6), or patients' preference (n = 1). Thirty-nine (78%) patients received the SBRT treatment. The 1-year OS and PFS were 64% (95% CI: 50%-76%) and 34% (95% CI: 22%-48%), respectively. Thirty grade 3 or 4 adverse events were observed during FOLFIRINOX. Two (5%) grade 3 or 4 adverse events after SBRT were observed. Two (5%) patients died due to a gastro-intestinal bleeding within three months after SBRT were observed. Six (12%) patients underwent a resection, all resulting in a complete (R0) resection. Two patients had a complete pathological response.

Interpretation: FOLFIRINOX followed by SBRT in patients with LAPC is feasible and shows relevant antitumor activity. In 6 (12%) patients a potentially curative resection could be pursued following this combined treatment, with a complete histological response being observed in two patients.

Keywords: Chemotherapy; Locally advanced pancreatic cancer; Radiotherapy; Surgery; Survival.

Associated data

ClinicalTrials.gov/NCT02292745