700 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). Interim analysis of this multicenter phase II trial evaluating the tolerability and efficacy of alternating FOLFOX and FOLFIRI (aFOLFIRINOX) in OA with metastatic pancreatic adenocarcinoma (mPDAC) indicated safety of the regimen. We now report updated study results including safety and survival endpoints. Methods: Eligible patients (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 (pts) could continue treatment thereafter at the discretion of their physician. The primary endpoint was rate of treatment-limiting grade ≥3 adverse events (TLAE) per CTCAE v5.0 in the first 8 weeks of therapy. TLAE were defined as treatment-related grade 3 non-hematologic AE persisting > 2 weeks despite best supportive care, grade 3 anemia or thrombocytopenia, grade >3 neuropathy, any grade > 4 AE, or AE requiring treatment discontinuation. The study was powered to detect a 20% improvement in TLAE compared to FOLFIRINOX. Secondary endpoints included progression free median age 75 (range 65-82); 31 pts had ECOG PS 0-1. The pre-specified primary endpoint was met - 24 pts (65%, 95% CI: 47%-80%) did not experience TLAE as defined above. 4 of 28 pts (14%) who received at least 1 full cycle of treatment had a TLAE, whereas 9 of 9 patients (100%) who received <2 cycles had a TLAE (p<0.001); 8 of those 9 pts were not evaluable for response. TLAE (e.g., neutropenia, anemia, hypokalemia, hypomagnesemia) were similar to AE reported with FOLFIRINOX or were disease-related (elevated bilirubin, pulmonary embolism). Of 29 pts evaluable for response, ORR was 14% (PR: n =4), disease control rate was 86% (SD: n =21). 12 pts (32.4%) completed 6 months of study treatment. Median PFS 6 mo, OS 8.9 mo. Emotional well-being improved over time (p=0.002); other QOL and mental health scores were stable over time. GA data will be presented at the meeting. Conclusions: OA with mPDAC treated with first-line aFOLFIRINOX did not experience excess or unexpected TLAE, and the alternating regimen was overall significantly less toxic. Enrolled pts were older than the average clinical trial pt but importantly tolerated treatment well with preserved QOL. This study demonstrates tolerability of aFOLFIRINOX with similar outcomes to historical data, suggesting this is a reasonable treatment option in this vulnerable patient population. Clinical trial information: NCT05360732 .
Winer et al. (2026) studied this question.