e21016 Background: Several reports suggest that cisplatin is associated with an increased risk of thromboembolism (TE). However, patients with solid tumors have multiple risk factors for TE and the excess risk of venous thromboembolic events (VTEs) with cisplatin-based chemotherapy as compared with non-cisplatin-based chemotherapy has not been well described. We performed a systemic review and meta-analysis of randomized controlled trials (RCTs) evaluating the incidence and risk of VTE associated with cisplatin-based chemotherapy. Methods: PubMed was searched for articles published from January 1, 1990 until December 31, 2010.The primary aim was to evaluate the association between treatment with cisplatin and VTEs in patients with cancer. Clinical trials that met the following criteria were included in the meta-analysis: (1) prospective randomized phase 2 and 3 trials of patients with cancer; (2) randomization to treatment with cisplatin versus a non-cisplatin containing chemotherapy regimen (3) available data on venous thromboembolic events. Data on all grade venous thromboembolic events was extracted. Study quality was calculated utilizing Jadad scores. Incidence rates, relative risks, and 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses included the impact of publication year, tumor type, and cisplatin dose. Results: A total of 8216 patients with a variety of advanced solid tumors from 38 RCTs were included for analysis. Among patients treated with cisplatin-based chemotherapy, the summary incidence of VTE was 1.64% (95% CI, 1.06–2.25). Patients treated with cisplatin-based chemotherapy had a significantly increased risk of VTE with a relative risk of 1.65 (95% CI, 1.25–2.18; P = .01) compared with controls. Exploratory subgroup analysis revealed the highest relative risk of VTE in patients receiving a weekly equivalent cisplatin dose >30 mg/m2 (2.64; 95% CI, 1.18–5.77; P = .02) and in studies reported during 2000-2010 (1.70; 95% CI, 1.27–2.28; P = .01). Conclusions: Cisplatin chemotherapy is associated with a significant increase in the risk of VTE in patients with advanced solid tumors compared with non-cisplatin chemotherapy.

Background: Immune-based strategies involving T-cell activation have recently shown significant activity in multiple tumor types. The presence of immune elements in breast cancers has prognostic and predictive impact. Thus, strategies that optimize the interplay between a breast cancer and the effected individual's immune system may be therapeutic. Interleukin-12 (IL-12), a pro-inflammatory cytokine, reverses immune escape mechanisms induced by myeloid derived suppressor and dendritic cells which, in turn, improves the function of activated CD8+ T cells and promotes tumor stroma collapse. Because tumor neoantigens may be generated in response to chemotherapy, IL12-mediated immune modulation may be optimal in patients with chemotherapy-sensitive metastatic breast cancer. Ad-RTS-hIL-12 (Ad) is a novel gene therapy candidate expressing IL-12 under the control of an orally-administered activator ligand, veledimex (V) through the proprietary RheoSwitch Therapeutic System® (RTS). Trial Design: Open-label, phase 1b/2, single-arm, single-center study of Ad+V in women with stable or responsive disease after ≥ 12-weeks of 1st or 2nd-line chemotherapy. Eligible patients will be placed on chemotherapy-holiday and enter the immunotherapy phase, consisting of a single cycle of Ad administered intratumorally (Day 1), along with V (80 mg QDx7). HER2-directed antibody therapy may be continued during the immunotherapy phase for women with HER2- disease. Key Eligibility Criteria: Women ≥18 years with histologically-confirmed locally advanced or metastatic breast cancer of any subtype who have achieved a partial response (PR) or stable disease (SD) to 1st or 2nd-line chemotherapy are eligible. Exclusion criteria include use of immunosuppressive drugs, compromised immune function, autoimmune disorder, or brain metastases. Specific Aims: To evaluate the safety and tolerability of Ad+V immunotherapy in eligible women. Secondary endpoints include 12 week overall response rate, 12 week disease control rate and the impact of treatment on exploratory immune biomarkers. Statistical Methods: Safety and efficacy will be evaluated separately for HER2-/HER2+ patients. Tumor response will be evaluated by RECIST v1.1 at 6 and 12 weeks. To ensure safety, stopping rules defined by grade 3/4 adverse events and12-week progression rate were adopted. Target Accrual: Up to 40 patients, including up to 8 patients (20%) with HER2+ disease. Summary: Ad+V is a novel gene therapy which controls local expression of IL-12 and may induce tumor stroma collapse and stimulation of an anti-cancer T cell immune response. The ability to regulate the production of IL-12 by modulating V dosing may result in an improved therapeutic index in combination with standard of care. The data from this study will directly inform future studies. Study Contact (Clinical Trials.gov: NCT02423902). Citation Format: McArthur HL, Page D, Proverbs-Singh T, Solomon S, Hudis C, Norton L, Patil S, Barrett JA, Lebel F. Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-01-05.

Background: Our aim was to study what roles β‐Catenin (β‐Cat) and tyrosine 654 phosphorylation of β‐Cat were playing in liver cancer (HCC). Design: Protein from 28 HCC cases and 3 cases without HCC (controls) was analyzed by western blots. Results: Of the 28 samples, 1 was poorly (P), 20 were moderately (M) and 5 were well (W) differentiated with 2 of unknown (U) status. 5/28 were fibrolamellar (FL). Only P or M tumors showed invasion (I). Of the non‐cirrhotic samples, I HCC had higher levels of tyr654 compared to non‐I. Of non‐cirrhotics and non‐FL HCC, M HCC had higher levels of tyr654 than W. Interestingly, W had higher levels of total β‐Cat. FL HCC had highest levels of tyr654 but lowest β‐Cat. HCC w/mutations at exon 3 had high tyr654 and high total β‐Cat. Conclusions: Tyr654 may be useful to differentiate M from W HCC and I from non‐I HCC. Also, FL HCC may have increased levels of tyrosine kinases inducing the phosphorylation of β‐Cat at tyr654. We found no correlation between β‐Cat mutations and differentiation, invasion or cirrhosis status.

e19621 Background: Women with hormone receptor positive (HR+) breast cancer can benefit from chemotherapy (CTX). Unnecessary therapy can adversely affect patient morbidity.. While tumor biology affects decision making, patient perception of cancer recurrence is also important. In this study we determine whether women with HR+ tumors (>1cm) who undergo CTX, have stronger beliefs in the efficacy of CTX than women who do not get therapy. Methods: Women participating in a Breast Cancer Patient Assistance Trial in 2006-2010 were surveyed about their cancer knowledge and beliefs about its treatment; charts were abstracted 6 months later to measure treatments received. A Nottingham Prognostic indicator (NPI), which uses stage, tumor size, and lymph node involvement was calculated. Chi-square and logistic regression analyses examined associations between receipt of CTX and tumor stage, NPI, physician recommendation, patient demographics and beliefs about CTX. Results: Women with HR+ tumors 130/211(62%) received CTX and 197/211(93%) received hormonal therapy. Gene array analysis was performed in 46/211 (22%), and of these (7/46 [15%]) had high recurrence scores and received CTX. Women treated with CTX vs those without CTX were younger (mean 52.5 yrs vs 62.3 yrs, p<0.0001), had higher stage cancer (stage II: 65% vs 23%, p<0.0001), worse NPI (poor prognosis:15% vs 2% p<0.0001), more physician recommended CTX (92% vs 34%, p<0.0001) and increased concern about recurrence without CTX (very worried 70% vs 15%; p<0.0001). Multivariate analysis found that physician recommendation, poor NPI and moderate NPI were most strongly associated with receiving CTX [RR= 3.2, (95% CI:1.8-5.6), 1.7, (95%CI:1.3-2.2); 1.6, (95%CI:1.2-2.0)], respectively, followed by women’s worry (RR=1.3; 95%CI: 1.0-1.6), and belief that CTX allows women to live longer (RR=1.1; 95%CI: 1.0 - 1.2). Older age was associated with less use of CTX (RR= 0.99; 95%CI: 0.978-.995). Conclusions: Physician recommendation, disease severity, concerns about recurrence and beliefs about CTX’s effectiveness influence the utilization of CTX in HR+ breast cancer. Patients may benefit from education to make informed decisions.