A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted.
Objectives
Industry‐supported decision impact studies demonstrate that Oncotype Dx (ODX) changes treatment recommendations (TR) in 24–40% of hormone receptor+/HER2− patients. ODX is not reimbursed by third‐party payers in Australia, potentially resulting in more selective use. We sought to evaluate the impact of self‐funded ODX on TRs.
Methods
Data collected included demographics, tumor characteristics, indication for ODX and pre‐ and post‐recurrence score (RS) TR. Primary endpoint was frequency of TR change and associations with TR change were sought.
Results
Eighteen physicians contributed 382 patients (median age 54). A total of 232 (61%) of tumors were T1 and were grade 1, 2 and 3 in 49 (13%), 252 (66%) and 79 (21%). A total of 257 (67%) were node negative. Assay indications were: confirm need for chemotherapy (CT) (36%), confirm omission of CT (40%) and genuine equipoise (24%). RS was low (≤17) in 55%, intermediate (18‐31) in 36% and high (≥32) in 9%. Thirty‐eight percent of patients had TR change post‐ODX. Sixty‐five percent of patients recommended CT pre‐ODX changed to hormone therapy alone (HT)—more likely if lower grade and if ER and/or PR > 10%. Fourteen percent of patients with pre‐ODX TR for HT added CT—more likely if ER and/or PR ≤10% and if Ki67 > 15% Overall, TR for CT decreased from 47% to 24%.
Conclusion
Patient‐funded ODX changed TRs in 38% of patients, de‐escalating 65% from CT to HT and adding CT to 14% of those recommended HT. These changes were greater than an industry‐funded study suggesting that physicians can identify situations where the assay may influence decisions.
228 Background: GEM-based treatment is a standard treatment for metastatic pancreas cancer. Monotherapy efficacy is only modest, and outcomes are improved by combination treatment or the non-GEM FOLFIRINOX triplet. There is a need for biomarkers to select between these divergent options. hENT1 is a potential predictive marker of benefit from GEM, but conflicting results have been observed in studies that have evaluated resected and metastatic pancreatic cancer. This principal objective of this study was to evaluate hENT1 prospectively as a predictive marker in GEM and non-GEM treated patients. Methods: Patients with previously untreated metastatic pancreatic adenocarcinoma and tumour tissue available for hENT1 testing were randomized between GEM (1,000 mg/m2 D1, 8, 15 Q4w) or FOLFOX (oxaliplatin 85 mg/m2, 5-fluorouracil (5FU) 400 mg/m2, leucovorin 400 mg/m2 D1 and 5FU 2,400 mg/m2over 46 hours D1-3) until disease progression or unacceptable toxicity. Tumor samples were tested prospectively for hENT1 by immunohistochemistry. The primary endpoint was progression-free survival (PFS). Results: The study was open from July 2011 to February 2013, but closed after 16 of the planned 80 patients were enrolled. 1 patient who died before treatment was excluded from the outcome analysis. 7/16 patients were hENT1 high (43.8%, 95%CI 23.1-66.8%). In the GEM arm (n=7), the 4 who were hENT1 high had longer PFS and overall survivals (OS) than those who were hENT1 low (median PFS 5.7 vs. 1.8 months; median OS 13.9 vs. 3.5 months), whereas outcomes were similar with FOLFOX for both hENT1 groups. There were no unexpected adverse events. Conclusions: This prospective study showed a longer survival in those patients with high hENT1 treated with GEM. There was no difference in survival according to hENT1 expression in patients treated with FOLFOX. Given the small sample size this may be due to chance, but supports the need for further research into the predictive value of hENT1. Clinical trial information: ACTRN12610001047088.[Table: see text]
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