Redefining the use of a first-line FOLFIRINOX-like regimen in older patients with metastatic pancreatic cancer.

681 Background: Prospective elderly-specific data for treating pancreatic cancer are scarce. First-line treatment with triplet chemotherapy (e.g., FOLFIRINOX) is often too toxic for older adults (OA). An alternating regimen of FOLFOX and FOLFIRI (aFOLFIRINOX) has demonstrated efficacy and decreased toxicity in patients with colon cancer. This ongoing multicenter phase II trial evaluates the tolerability and efficacy of aFOLFIRINOX in OA with metastatic pancreatic adenocarcinoma (mPDAC). Herein we report the interim safety analysis results. Methods: Eligible patients (goal n=37) ≥65 years old with measurable untreated mPDAC, ECOG PS 0-2, receive standard doses of FOLFOX alternating with FOLFIRI every 2 weeks for up to 6 months. Patients can continue treatment thereafter at the discretion of their physician. The primary endpoint is rate of treatment-limiting grade ≥3 adverse events (TLAE) per CTCAE v5.0 in the first 8 weeks of therapy. These toxicities are defined as treatment-related grade 3 non-hematologic AE persisting > 2 weeks despite best supportive care, grade 3 anemia or thrombocytopenia, grade >3 neuropathy, or any grade > 4 AE. The study is powered to detect a 20% improvement in grade ≥3 TLAE: null vs alternate: 45% vs 65% of patients without TLAE at 8 weeks. Secondary endpoints include progression free & overall survival (PFS & OS) and objective response rate (ORR). FACT-G and PROMIS-10 quality of life (QOL) surveys and geriatric assessments are collected and will be correlated with treatment outcomes. Results: 21 eligible patients were included in the interim safety analysis: 11 male, 10 female; median age:73 (range 65-82); 18 patients had ECOG PS 0-1. 16 (76%) patients did not experience TLAE as defined above. TLAE included neutropenia, thromboembolism, and hypokalemia, and are similar to reported toxicity with FOLFOX and FOLFIRI in this patient population. One patient died of their disease within 8 weeks of treatment initiation and another within 2 weeks due to pulmonary embolism deemed unrelated to treatment. Of the 18 patients evaluable for response, ORR was 11% (partial response: n =2), Disease Control Rate was 89% (stable disease: n =14). 7 patients completed 6 months of treatment on study. Conclusions: The interim safety analysis of this clinical trial fulfilled the predefined futility rule without excess treatment-limiting or unexpected toxicity among OA with mPDAC treated with first-line aFOLFIRINOX, suggesting this may be a reasonable treatment option in this patient population. Trial is ongoing for evaluation of efficacy data of this regimen. Clinical trial information: NCT05360732 .