Citations

e15616 Background: Cholangiocarcinoma (CCA) is a progressively fatal disease with an annual incidence of 1-2 cases per 100,000 people in the USA. Complete surgical resection is the only curative option for CCA. However, the majority of patients (pts) have advanced disease at diagnosis, and those undergoing resection often develop local or distant recurrence. Gemcitabine and Cisplatin remains the only standard chemotherapeutic regimen for advanced CCA. Alternative and improved therapies are critically needed. Gemcitabine/nab-Paclitaxel (GA) is a regimen that has become standard therapy in advanced pancreatic cancer (PDAC). Given the morphologic and histologic similarities between PDAC and CCA, this regimen has been used in advanced CCA, but no data exists regarding its efficacy in this disease. The goal of our study is to evaluate the Mayo Clinic experience with GA for the treatment of metastatic CCA. Methods: We retrospectively analyzed records from adult pts at Mayo Clinic with metastatic cholangiocarcinoma who received at least 2 cycles of GA. Our aims were to assess the progression-free survival (PFS), overall survival (OS) and disease response. Results: We analyzed 9 pts, 3 male and 6 female. The median age at diagnosis was 50 years (range 41-64). Six pts had metastatic disease at diagnosis while 3 underwent surgery with subsequent distant disease recurrence. Pts received a median of 2 lines (range 0-5) of systemic therapy prior to receiving GA, and a median of 2 cycles (range 2-15) of GA. At the time of our analysis, 4 of the 9 pts (44%) had died. The median OS from initiation of GA was 7.3 months (95% CI 1.7- 12.9) and median PFS from initiation of GA was 4.7 months (95% CI 0.48-8.9). The best overall responses using RECIST criteria were: partial response in 1 (11%), stable disease in 5 (55%) and disease progression in 3 (33%) pts. One pt remained on therapy 14.9 months after initiating GA. Conclusions: In our study, the combination of gemcitabine and nab-paclitaxel has demonstrated similar OS and PFS as other systemic therapies. To the best of our knowledge, this is the first report of this regimen in CCA. Ongoing, prospective trials are currently evaluating this regimen in advanced CCA.

TPS3630 Background: In metastatic colorectal cancer with deficient DNA mismatch repair (MMR), anti-PD-1 antibody monotherapy produced high tumor response rates and extended progression-free survival compared to lack of benefit for proficient MMR tumors (Le, M, et al, NEJM 2016). We propose a phase III randomized trial to determine if the addition of the anti-PD-L1 antibody, atezolizumab (Genentech™), to adjuvant FOLFOX can improve patient disease-free survival (DFS) vs FOLFOX alone in patients with stage III colon cancers with dMMR or microsatellite instability (MSI). By blocking the PD-1/PD-L1 interaction, atezolizumab may activate T cells, thereby, restoring their ability to detect and attack tumor cells. Limited data suggest that FOLFOX may increase intratumoral cytotoxic CD8+ T cells that may serve as ‘immune priming.’ Methods: Patients with curatively resected stage III colon carcinomas with evidence of dMMR or MSI will be randomized to modified FOLFOX6 for 6 months (12 cycles) alone or combined with atezolizumab (840 mg IV q2 wk) continued as monotherapy for an additional 6 months (total duration of 12 months). Patients will be stratified by T, N stage and tumor sidedness. Local testing for MSI or MMR proteins is allowed. Atezolizumab must begin by/with cycle 2. The targeted accrual goal of 700 patients provides 90% power to detect an effect size expressed as hazard ratio of 0.6 for the primary endpoint DFS at two-sided alpha of 0.05. Interim analyses are planned at 50% and 75% of events. Secondary endpoints include overall survival, treatment tolerability, and quality of life. This study will be conducted by the Alliance for Clinical Trials in Oncology. The protocol has been approved by NCI CTEP and is expected to be activated in mid 2017. Clinical trial information: NCT02912559.