Analysis of Clinical Predictive Factors Affecting the Outcome of Second-Line Chemotherapy for Gemcitabine-Refractory Advanced Pancreatic Cancer

Abstract

Background/Aims: The benefit of second-line chemotherapy (SL) after failed first-line chemotherapy (FL) in patients with advanced pancreatic cancer has not yet been established. We evaluated the clinical characteristics affecting the benefits of SL compared to best supportive care (BSC), identified the prognostic factors, and ultimately devised a model of clinical parameters to assist in making decision between SL and BSC after the failure of gemcitabine-based FL. Methods: The records of patients who received gemcitabinebased FL for advanced pancreatic cancer at Yonsei University Hospital between January 2010 and December 2015 were retrospectively reviewed. Significant clinical parameters were assessed for their potential as predictive factors. Results: SL patients received a longer duration of FL compared with BSC patients with median duration being 16.0 weeks (range, 8.0 to 26.0 weeks) and 8.0 weeks (range, 4.0 to 16.0 weeks), respectively (p<0.001). When the SL group was stratified by their modified overall survival (mOS) (longer and shorter than 6 months), we found significant differences for several clinical factors, namely, metastasis to the peritoneum (p<0.001), number of metastases (p<0.001), thrombotic events (p=0.003), and level of carbohydrate antigen 19-9 (CA19-9; p=0.011). In multivariate analysis, more than one site of metastasis, occurrence of thrombotic event during FL, and a CA19-9 level above 90 U/mL were significant independent prognostic factors for mOS in the SL group (p<0.05). When an attempt was made to devise a prognostic nomogram, Harrell's C-index of the final prognosis prediction model was 0.62. Conclusions: SL may be beneficial for patients without peritoneal metastasis or thrombotic events who have a single metastasis and a level of CA19-9 less than 90 U/mL. This prognostic nomogram can be used to predict mOS be-fore the administration of SL after the failure of gemcitabinebased FL.

The clinical outcomes of second-line chemotherapy in patients with advanced pancreatic cancer: a retrospective study

“…Several studies have reported factors that can predict the survival outcomes of patients who undergo second-line chemotherapy [9,10,[14][15][16][17][18]. Among several clinical and biochemical variables, PS is one of the most common and important prognostic factors in patients receiving second-line chemotherapy [9,[14][15][16][17].…”

Efficacy and tolerance of LV5FU2-carboplatin chemotherapy in patients with advanced pancreatic ductal adenocarcinoma after failure of standard regimens

“…Consistently, several studies reported second-line chemotherapy to be less efficient in patients with higher metastatic extent, particularly peritoneal metastases. 25,26 In addition, general condition compatible with full chemotherapy doses and slower disease evolution (diagnosis > 18 months before treatment initiation) was associated with prolonged tumor control under LV5FU2-carboplatin. Similarly, in a previous series, second-line chemotherapy achieved longer OS in patients who had longer first-line treatment duration.…”

Prognostic analysis and outcomes of metastatic pancreatic cancer patients receiving nab‐paclitaxel plus gemcitabine as second or later‐line treatment

“…43 In this series patients had received gemcitabine-based adjuvant or first line treatment (which were considered together) and went on to receive fluoropyrimidine-based (FOLFORINOX, FOLFOX, Cape/OX, or folinic acid/etoposide/cisplatin-FEP) second line. In another series from Taiwan, 43 decision-making and providing valuable information for discussions with pretreated metastatic pancreatic cancer patients and their families.…”

“…Therefore, a careful evaluation and fair discussion of potential risks and benefits of second‐line treatment with patients and their families is mandatory and, perhaps, more important than the specific regimen selected. Individual prognostic factors have been proposed in this setting (PS, tumor burden, treatment response and duration of first‐line therapy, second‐line therapy regimen, and circulating biomarkers) and attempts have been made to integrate them into prognostic nomograms 43,44 . In a large retrospective Korean series, a nomogram for predicting OS on second‐line chemotherapy for mPC was devised based on number of metastatic lesions, presence of peritoneal metastases, occurrence of thrombotic events during first line, and CA19.9 levels; Harrel's C values for the development and validation cohorts were 0.62 and 0.56, respectively 43 .…”