Background: Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear.Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution. Results: Fifty-six patients were included and the majority had intrahepatic aCC. A total of 80% received first-line gemcitabine-based therapy. Second-line therapy consisted of GEM-P (19.6%), GEM-FU (28.6%), FU-combo (37.5%), and others (14.3%). Median PFS was 2.7-month (95% CI, 2.3-3.8 months) with a median OS of 13.8 months (95% CI, 12-19.3 months) and a disease control rate of 50%. No significant difference in survival was identified between the four treatment groups.Conclusions: This study revealed a 2.7-month PFS, 50% disease control rate, and potential survival benefit with second-line treatment. Options for second-line systemic therapy include GEM-FU, FU-combo, GEM-P if not given in the first-line setting. Targeted therapy with erlotinib or bevacizumab could be considered in addition to chemotherapy.
635 Background: Regorafenib was approved by the FDA on September 27, 2012 following the CORRECT trial demonstrating an overall survival (OS) benefit compared to placebo in pts with advanced treatment-refractory CRC (Grothey A. et al: Lancet. 2013;381:303-12). Little data exists regarding patient treatment outcomes outside of reported clinical trial data. Methods: Pts seen at MD Anderson Cancer Center with a diagnosis of gastrointestinal malignancies since October 1, 2012 were evaluated for regorafenib therapy; electronic clinic records were reviewed for pt treatment data, toxicity, and survival outcomes. Results: 61 pts were identified; 4 pts were determined to have GI malignancy other than CRC [appendiceal cancer (n=3) and duodenal cancer (n=1)] and were omitted from this analysis. Median age was 58 years (range 30.5-83.3), M:F 37:20 (65%:35%), KRAS non-mutant/ KRAS mutant 26/31 (46%:54%), BRAF mutant n=3 (5%); Median time from diagnosis of metastatic disease to initiation of regorafenib therapy was 27.7 months (range 5.9-112.3); 8 pts (14%) had enrolled in clinical trials prior to starting regorafenib. The initial starting dose was 160 mg (n= 38, 66.7%), 120mg (n=18, 31.5%), and 80mg (n=1, 1.8%) respectively. Dose reductions or interruptions were required in 25 pts (43.8%); 14 patients (24.5%) discontinued therapy due to toxicity. The most common grade 3 adverse event was hand-foot reaction (n=12; 21%). One pt initiated on 120 mg was able to tolerate dose escalation to 160mg. Seven pts (12.2%) had stable disease radiographically for more than 2 months and 2 had a confirmed partial response (3.5%). Median OS was 9.1 months (95% C.I. 5.3-12.8) and median time on regorafenib therapy was 2.2 months (range 0.2-10.3). Following regorafenib discontinuation 12 pts (21%) were enrolled on phase I trials. Conclusions: In this pt population palliative regorafenib therapy was associated with modest efficacy and significant toxicity. Dose reductions or interruptions were common (43.8%) even despite a large number of pts being initiated on a dose lower than the recommended initial dose (33.3%). Further studies may be required to determine the optimal tolerable dose in pts with advanced CRC.
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