Abstract 425P
Background
Chemoradiation (CRT) with carboplatin and paclitaxel (CP) is the gold standard neoadjuvant treatment for esophageal (E) and gastroesophageal junction (GEJ) cancers, but 10-year CROSS data shows overall distant relapse rate remains high (40%). The addition of full-dose chemotherapy prior to CRT could provide enhanced local and early systemic disease control. We evaluated induction FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) followed by CRT and surgery in patients (pts) with E/GEJ cancers and, here, present mature safety and efficacy data.
Methods
This single-arm, phase II clinical trial evaluated 6 weeks of induction mFOLFOX6 followed by 5.5 weeks of CRT with CP and 41.4-45 Gy radiation and surgery in clinically staged II-III E/GEJ cancers. Primary endpoint was 2-year progression-free survival (PFS), defined as time from induction initiation to disease relapse or death. Pathologic response, overall survival (OS), and safety were secondary outcomes.
Results
Median follow-up was 4.4 years. 42 pts enrolled; median age was 64 years and 78.6% were male. Most primary tumors (68.3%) were in the GEJ and 95.2% were adenocarcinoma. Treatment completion rate was high: 97.6% completed all FOLFOX cycles and received at least the pre-specified RT dose. 37 pts (88.1%) underwent surgery, all of which were R0 resections. 81.1% of surgical specimens were node-negative and 24.3% showed a pathological complete response (pCR). Median PFS was 3.53 years and 2-year PFS was 66.7%; median OS was 5.32 years. Distant relapse occurred in 26%. There were no ≥ 3 treatment-related adverse events that occurred in >5% of patients other than cytopenias and no deaths during induction or CRT.
Conclusions
FOLFOX followed by CRT with CP and surgery demonstrated a good safety profile and an impressive 63.8 month median OS. Though pCR rates were similar to historical comparisons, the 100% R0 resection rate, high rates of node-negative pathology and relatively low distant relapse rates may have contributed to survival outcomes. Given findings from CALGB 80803 and those here, FOLFOX could be considered during neoadjuvant treatment for locally advanced E/GEJ cancers.
Clinical trial identification
NCT03110926.
Legal entity responsible for the study
University of Rochester.
Funding
University of Rochester.
Disclosure
M.S. Noel: Financial Interests, Advisory Role: Celgene, Ipsen, Taiho Pharmaceutical; Financial Interests, Speaker’s Bureau: Celgene, Daiichi Sankyo/AstraZeneca, Taiho Pharmaceutical; Financial Interests, Other, Research Funding: Erytech Pharma. A.F. Hezel: Financial Interests, Advisory Role: AstraZeneca; Financial Interests, Expert Testimony: LegalMed. R.F. Dunne: Financial Interests, Advisory Board: Exelixis Inc., Merck & Co., Toray Industries Inc. All other authors have declared no conflicts of interest.