CHICAGO—Neoadjuvant chemotherapy cannot match upfront surgery for survival for resectable pancreatic cancer, a small randomized trial shows.
Unexpectedly, patients who had surgery for the first time lived more than a year longer than those who received a short course of FOLFIRINOX chemotherapy before surgery. This result is particularly surprising given that neoadjuvant therapy was associated with a higher rate of negative surgical margins (R0) and that more patients in the treatment group achieved node-negative status.
“Additional follow-up may better explain the long-term impact of improvements in R0 and N0 in the neoadjuvant group,” said Knut Jorgen Laborie, MD, University of Oslo, Norway, American Society of Clinical Oncology. ASCO) meeting. “The results do not support the use of neoadjuvant FOLFIRINOX as standard treatment for resectable pancreatic cancer.”
This result surprised Andrew H. Ko, MD, of the University of California, San Francisco, who was invited to the discussion, and he agreed that they do not support neoadjuvant FOLFIRINOX as an alternative to upfront surgery. But they also do not exclude this possibility. Due to some interest in the study, it is not possible to make a definitive statement about the future status of FOLFIRINOX neoadjuvant.
Ko noted that only half of the patients completed four cycles of neoadjuvant chemotherapy, “which is much lower than what I expected for this group of patients, for whom four cycles of treatment is generally not very difficult…. ..Second, why Do more favorable surgical and pathologic outcomes [R0, N0 status] lead to a trend toward worse outcomes in the neoadjuvant group? understand the cause and ultimately switch to gemcitabine-based regimens.”
“Therefore, we really cannot draw firm conclusions from this study about the specific impact of perioperative FOLFIRINOX on survival outcomes… FOLFIRINOX remains available, and several ongoing studies will hopefully shed light on its potential in resectable surgery.” Diseases.”
Laborie noted that surgery combined with effective systemic therapy provides the best results for resectable pancreatic cancer. Traditionally, the standard of care has included upfront surgery and adjuvant chemotherapy. However, neoadjuvant therapy followed by surgery and adjuvant chemotherapy has begun to gain popularity among many oncologists.
Neoadjuvant therapy offers many potential benefits: early control of systemic disease, improved delivery of chemotherapy, and improved histopathological outcomes (R0, N0), Laborie continued. However, to date, no randomized trial has clearly demonstrated a survival benefit of neoadjuvant chemotherapy.
To address the lack of data in randomized trials, researchers from 12 centers in Norway, Sweden, Denmark and Finland recruited patients with resectable pancreatic head cancer. Patients randomized to upfront surgery received 12 cycles of adjuvant-modified FOLFIRINOX (mFOLFIRINOX). Patients receiving neoadjuvant therapy received 4 cycles of FOLFIRINOX followed by repeat staging and surgery, followed by 8 cycles of adjuvant mFOLFIRINOX. The primary endpoint was overall survival (OS), and the study was powered to show an improvement in 18-month survival from 50% with surgery upfront to 70% with neoadjuvant FOLFIRINOX.
Data included 140 randomized patients with ECOG status 0 or 1. In the first surgical group, 56 of 63 patients (89%) underwent surgery and 47 (75%) began adjuvant chemotherapy. Of the 77 patients assigned to neoadjuvant therapy, 64 (83%) initiated therapy, 40 (52%) completed therapy, 63 (82%) underwent resection, and 51 (66%) began adjuvant therapy.
Grade ≥3 adverse events (AEs) were observed in 55.6% of patients receiving neoadjuvant chemotherapy, mainly diarrhea, nausea and vomiting, and neutropenia. During adjuvant chemotherapy, approximately 40% of patients in each treatment group experienced grade ≥3 AEs.
In an intention-to-treat analysis, median overall survival with neoadjuvant therapy was 25.1 months compared with 38.5 months with surgery upfront, and neoadjuvant chemotherapy increased the risk of survival by 52% (95% CI 0.94–2.46, P=0.06). The 18-month survival rate was 60% with neoadjuvant FOLFIRINOX and 73% with surgery upfront. Per-protocol assays yielded similar results.
Histopathologic results favor neoadjuvant chemotherapy as 56% of patients achieved R0 status compared with 39% of patients upfront surgery (P = 0.076) and 29% achieved N0 status compared with 14% of patients (P = 0.060). Per-protocol analysis showed statistically significant differences with neoadjuvant FOLFIRINOX in R0 status (59% vs. 33%, P=0.011) and N0 status (37% vs. 10%, P=0.002).
Charles Bankhead is a senior oncology editor and also covers urology, dermatology and ophthalmology. He joined MedPage Today in 2007.
The study was supported by the Norwegian Cancer Society, the Regional Health Authority of South-East Norway, the Swedish Sjoberg Foundation and Helsinki University Hospital.
Ko 披露了与 Clinical Care Options、Gerson Lehrman Group、Medscape、MJH Life Sciences、Research to Practice、AADi、FibroGen、Genentech、GRAIL、Ipsen、Merus、Roche、AbGenomics、Apexigen、Astellas、BioMed Valley Discoveries “Bristol Myers Squibb” . Celgene, CrystalGenomics, Leap Therapeutics and other companies.
Source Citation: Labori KJ et al. “Short-course neoadjuvant FOLFIRINOX versus upfront surgery for resectable pancreatic head cancer: a multicenter randomized phase II trial (NORPACT-1),” ASCO 2023; Abstract LBA4005.
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Post time: Sep-22-2023