Third-line platinum-based chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma

BACKGROUND/OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with limited later-line therapeutic options. This retrospective study aimed to evaluate the efficacy and safety of platinum-based chemotherapy as third-line treatment for metastatic PDAC. METHODS: We analyzed 102 patients who received third-line systemic treatment for PDAC between 2018 and 2023 across five medical centers in Taiwan. All patients had previously received first-line gemcitabine-based therapy and second-line nanoliposomal irinotecan with 5-fluorouracil and leucovorin. Overall, one group (N = 40) received platinum-based regimens, whereas the other group (N = 62) received non-platinum-based treatments. Survival outcomes and treatment-related toxicities were compared between the groups. RESULTS: The median overall survival (OS) duration was 5.8 months (95 % CI, 3.3-8.3) for the platinum group and 4.3 months (95 % CI, 3.5-5.0) for the non-platinum group, without a statistically significant difference (HR, 0.74, 95 % CI: 0.46-1.18, p = 0.21). The median time-to-treatment failure was 2.4 months (95 % CI, 1.6-3.2) and 2.1 months (95 % CI, 1.3-2.9), respectively (HR, 0.85, 95 % CI: 0.57-1.28, p = 0.44). Subgroup analyses suggested that younger age and no history of pancreatectomy tended to associate with better OS following platinum-based treatment. However, the platinum group experienced a higher incidence aspartate aminotransferase elevation (13 % vs. 2 %, p = 0.033) and increased creatinine (13 % vs. 2 %, p = 0.033) levels than the non-platinum group. CONCLUSIONS: This study showed that a platinum-based third-line chemotherapy regimen for patients with metastatic PDAC did not confer a significant survival advantage over non-platinum-based regimens. Platinum-based regimens are associated with modestly increased treatment-related toxicities, thus potentially limiting their tolerability in these heavily pretreated patients.