Introduction
First-line FOLFIRINOX or gemcitabine plus nab-paclitaxel (GNP) have improved the survival outcomes of patients with advanced pancreatic cancer (APC) and nano-liposomal irinotecan (nal-IRI) plus 5-FU/leucovorin is proven as the second-line agents.
Aims & Methods
The current study aims to assess the efficacy of third-line palliative chemotherapy in APC.
Medical records were retrospectively reviewed in a single tertiary hospital between 2012 and 2021. We enrolled patients with APC who experienced progression after the second-line chemotherapy following the first-line FOLFIRINOX or GNP. To define the efficacy of the third-line chemotherapy, Cox-regression analysis was performed. To identify the clinical factors affecting the survival, multivariable logistic regression analysis was also performed.
Results
Total 141 patients were enrolled. The median age at diagnosis was 61.8 years (range 36.0 – 86.0), and males were 54.9% (n=78). The first-line chemotherapy regimen was FOLFIRINOX (95, 67.4%) and GNP (46, 32.6%). The second-line chemotherapy regimen was FOLFIRINOX (38, 27.0%), GNP (74, 52.5%), and others (29, 20.4%). Regarding the third-line regimen, TS-1 and nal-IRI plus 5-FU/leucovorin were 69 (27.0%) and 53 (37.6%). The median overall survival (OS) from diagnosis was 18.0 months (95% confidence interval (CI), 15.3 – 20.7). The median OS and median progression-free survival after the third-line treatment were 14.6 (95% CI, 12.1 – 17.0) and 7.3 weeks (95% CI, 6.3– 8.3). About the best tumor response during the third-line chemotherapy, there was no complete response, 2 (1.4%) with a partial response, 41 (29.1%) with stable disease, and 80 (56.7%) with progressive disease. Consequently, the disease control rate in the third-line treatment was 30.5%. Of the patients with the third-line chemotherapy, the following clinical factors affected OS; ECOG of 2 at third-line chemotherapy (HR: 2.64, 95% CI: 1.58-4.42; p <0.001), serum CA19-9 level ≥ 1,000 U/ml before the third-line chemotherapy (HR: 1.67, 95% CI: 1.11-2.52; p=0.014), duration of the second-line chemotherapy < 19 weeks (HR: 1.51, 95% CI: 1.03-2.21; p=0.034), and peritoneal seeding before the third-line chemotherapy (HR: 1.53, 95% CI: 1.03-2.25; p=0.033).
|
| Univariable analysis
| Multivariable analysis
|
|
| Hazard ratio (95% CI)
| P
| Hazard ratio (95% CI)
| P
|
Gender
| Male | 1.425 (1.010-2.010)
| 0.044
| 1.330 (0.911-1.943)
| 0.140 |
ECOG at third-line CTx
| Score 2
| 2.257 (1.413-3.607)
| 0.001 | 2.639 (1.576-4.419)
| <0.001 |
CA 19-9 level before third-line CTx
| ≥1,000U/ml
| 1.540 (1.061-2.235)
| 0.023 | 1.672 (1.109-2.522)
| 0.014 |
Duration of second-line CTx
| < 19 weeks
| 1.749 (1.215-2.516
| 0.003 | 1.508 (1.031-2.206)
| 0.034 |
Peritoneal seeding before third-line CTx
| Positive
| 1.429 (1.009–2.023)
| 0.044 | 1.526 (1.034-2.253)
| 0.033 |
Conclusion
The current study suggested that proceeding with the third-line chemotherapy could be recommended in some patients. There is no difference in survival rate according to the type of the third-line chemotherapy regimen. ECOG 0 or 1, CA 19-9 <1,000U/ml, duration of second-line chemotherapy ≥ 19 weeks, and no peritoneal seeding showed significantly more benefit from the third-line therapy.
References
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