No improved OS in pancreatic cancer after neoadjuvant mFOLFIRINOX

Although neoadjuvant chemotherapy improved surgical outcomes in patients with resectable pancreatic head cancer, it did not improve overall survival (OS) in the phase 2 NorPACT-1 trial.

In patients with resectable pancreatic cancer, complete resection and effective systemic therapy achieve the best outcomes. Upfront surgery followed by adjuvant chemotherapy, preferably mFOLFIRINOX, is the current standard-of-care. However, neoadjuvant treatment may offer early control of systemic disease, improved delivery of chemotherapy, and/or improved surgical outcomes (R0 and N0 resection rates). The aim of the phase 2, unblinded NorPACT-1 trial (NCT02919787) was to test the efficacy of neoadjuvant mFOLFIRINOX treatment for resectable pancreatic head cancer. Prof. Knut Labori (Oslo University Hospital, Norway) presented the results [1].

The study randomised 140 participants with resectable pancreatic head cancer to upfront surgery followed by 12 cycles of mFOLFIRINOX or 4 cycles of mFOLFIRINOX followed by surgery and 8 additional cycles of mFOLFIRINOX. The primary endpoint was the OS rate 18 months after randomisation (in the intention-to-treat [ITT] population). In the neoadjuvant arm, 77% of participants underwent resection compared with 89% in the upfront surgery arm; 66% of participants in the neoadjuvant arm started adjuvant chemotherapy compared with 75% in the upfront surgery arm.

Neoadjuvant treatment did not improve OS in the ITT population. At 18 months, 60% of participants were alive in the neoadjuvant arm versus 73% in the upfront surgery arm (P=0.1). The median OS per protocol was 23.0 versus 34.4 months, respectively.

On the other hand, neoadjuvant mFOLFIRINOX did improve histological outcomes. R0 (per protocol) was 59% in the neoadjuvant arm versus 33% in the upfront surgery arm (P=0.011); N0 was 37% versus 10% (P=0.002). Neoadjuvant mFOLFIRINOX also resulted in more grade 3–4 adverse events compared with adjuvant mFOLFIRINOX (55.6% versus 40%).

Prof. Labori concluded that while there was an improvement in histological outcomes with neoadjuvant mFOLFIRINOX, this improvement was not translated into better survival. “These results do not support neoadjuvant mFOLFIRINOX as a standard-of-care in resectable pancreatic cancer. However, additional follow-up may better elucidate the long-term effects of the improvement in R0 and N0 rates in the neoadjuvant arm.”

1. Labori KJ, et al. Short-course neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer. A multicenter randomized phase-2 trial (NORPACT-1). Abstract LBA4005, ASCO Annual Meeting 2023, 2–6 June, Chicago, USA.

 

Copyright ©2023 Medicom Medical Publishers



Posted on 2 August, 20232 August, 2023