Abstract B135: The significance of third-line chemotherapy for pancreatic ductal adenocarcinoma: A single-center retrospective analysis
Akihiro Ohba, Hirotoshi Noda, Naoya Ishibashi, Rin Inamoto, Hiroki Sakamoto, Kunihiro Fushiki, Kotoe Oshima, Takeshi Kawakami, Satoshi Hamauchi, Takahiro Tsushima, Tomoya Yokota, Kentaro Yamazaki, Hirofumi Yasui, Hirotoshi IshiwatariAbstract
Background:
GnP (gemcitabine and nab-paclitaxel), FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin), and NALIRIFOX (fluorouracil, leucovorin, liposomal irinotecan, and oxaliplatin) were established as the standard first-line chemotherapy for pancreatic ductal adenocarcinoma (PDAC). After GnP, nal-IRI + FU/LV (fluorouracil, leucovorin, and liposomal irinotecan) is used as standard second-line chemotherapy. Subsequent third-line FOLFOX (fluorouracil, leucovorin, and oxaliplatin) may be selected based on the patient's condition, but the survival benefit is unclear. Therefore, we conducted a retrospective analysis of the clinical significance of third-line FOLFOX at PDAC.
Methods:
We retrospectively assessed clinical outcomes of patients treated with FOLFOX between January 2018 and April 2025 at our center. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety. We also analyzed prognostic factors for OS and PFS.
Results:
A total of 125 patients were selected for this study. Median age was 68 (range 40–80); females were 40.8%; Eastern Cooperative Oncology Group Performance Status (PS) 0, 1, and 2 were 23.2%, 68.0%, and 8.8%, respectively; the primary tumor site was pancreatic head in 46.4%; and 84.0% of the patients had metastatic disease. Germline BRCA-mutated patients were not included. The median OS was 4.5 months (95% CI 3.9–5.2), and the median PFS was 1.9 months (95% CI 1.7–2.1). The ORR was 0.8%, and the disease control rate was 18.4%. The most common ≥ grade 3 adverse events were anemia (8.8%), neutrophil count decreased (5.6%), anorexia (6.4%), and fatigue (4.8%). Treatment-related death did not occur. PS 2 (HR 2.90, 95% CI 1.37–6.14, p = 0.005) and albumin < 3.0 g/dL (HR 2.67, 95%CI 1.48–4.85, p = 0.001) were identified as independent prognostic factors for OS. High-risk patients (PS 2 or albumin < 3.0g/dL, n = 24) had significantly shorter OS (2.8 vs. 5.0 months, p < 0.001) and PFS (1.1 vs. 2.0 months, p < 0.001) than non-high-risk patients (neither factor).
Conclusions:
Although third-line FOLFOX following first-line GnP and second-line nal-IRI + FU/LV for PDAC was feasible, it had limited efficacy in terms of OS and PFS. Particularly in high-risk patients (PS 2 or albumin < 3.0g/dL), caution may be warranted when initiating the third-line chemotherapy.
Citation Format:
Akihiro Ohba, Hirotoshi Noda, Naoya Ishibashi, Rin Inamoto, Hiroki Sakamoto, Kunihiro Fushiki, Kotoe Oshima, Takeshi Kawakami, Satoshi Hamauchi, Takahiro Tsushima, Tomoya Yokota, Kentaro Yamazaki, Hirofumi Yasui, Hirotoshi Ishiwatari. The significance of third-line chemotherapy for pancreatic ductal adenocarcinoma: A single-center retrospective analysis [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr B135.