Citations

8533 Background: BNET are a rare and frequently indolent group of neoplasms. Lobectomy is frequently done for patients with non-metastatic disease, and the role of adjuvant chemotherapy for patients with node positive disease (N+) is debated. Methods: Utilizing the National Cancer Database from 2004-2012 we identified 1682 patients with N+ non-metastatic BNET. All patients underwent primary resection, had pathologically confirmed diagnosis, complete follow up data, and were alive > 30 days following surgery. Overall survival (OS) was analyzed utilizing Kaplan-Meier curves, and log-rank tests were used to compare 2 groups of patients that differed based on receiving or not adjuvant chemotherapy. Subgroup analyses were performed based on histologic subtypes. Cox proportional hazards was performed to control for age, sex, race, grade, surgical margins, type of surgery, year of diagnosis, Charlson/Deyo Score, insurance, facility type, and location. Results: 651 patients with typical carcinoid (CT), 239 atypical carcinoid (ACT), 426 large cell neuroendocrine carcinoma (LCNEC), and 366 neuroendocrine carcinoma (NEC) were analyzed. The cohort median age was 61, and the female:male ratio was 1.8 for CT, ACT and NEC, and 1 for LCNEC 90% of patients were White and there were no significant differences amongst histologic subtypes. 6% of patients with CT received ADJ-CT, compared to 40% ACT, 42% NEC, and 70% LCNEC. In a multivariate analysis, only increasing age was associated with worse prognosis across all histologic subtypes, and non-academic facility for CT, and male sex for NEC. ADJ-CT was not associated with OS benefit for patients with ACT (HR 1.1; 95% CI 0.68-1.78; p:0.6), was associated with inferior OS in CT (HR: 3.8 (95% CI 1.9-7.0; p = 0.004) and NEC (HR: 2.15; 95% CI 1.5-3.0; p < 0.001), and may provide benefit for LCNEC (HR: 0.67; 95% CI 0.5-0.9; p = 0.009). Conclusions: Adjuvant chemotherapy was not associated with survival benefit for patients with node positive and non-metastatic BNET except for LCNEC, and may be harmful for patients with CT and NEC.

Objectives Prognostic factors for solid pseudopapillary neoplasms (SPN) of the pancreas have been incompletely defined in the literature. We aimed to use the National Cancer Database to describe survival and characterize prognostic factors in patients with pancreatic pseudopapillary neoplasms. Methods We identified 304 patients with pancreatic SPN diagnosed between 2004 and 2012 using the National Cancer Database. All patients were included in the survival analysis. Kaplan-Meier method, χ 2 , and log-rank tests were used for statistical analysis. Cox proportional hazard regression model was used for multivariate analysis. Results The median age at diagnosis was 36.5 years. Eighty-five percent of patients were female, 69% were white, and 25% were black. Metastases were observed in 5% of patients. Median tumor size was 5.1 cm. Ninety-two percent of patients underwent primary tumor resection. At 60 months, 98% of patients who underwent resection were alive, and 40% who did not undergo resection were alive. On multivariate analysis, female sex, resection of primary tumor, and absence of metastasis were correlated with improved survival. Conclusions Patients with SPN who undergo resection have an excellent survival at 5 years. Surgery should be considered in all patients with this diagnosis.

Purpose Data that guide selection of optimal local ablative therapy for the management localized hepatocellular carcinoma (HCC) are lacking. Because there are limited prospective comparative data for these treatment modalities, we aimed to compare the effectiveness of radiofrequency ablation (RFA) versus stereotactic body radiotherapy (SBRT) by using the National Cancer Database. Methods We conducted an observational study to compare the effectiveness of RFA versus SBRT in nonsurgically managed patients with stage I or II HCC. Overall survival was compared by using propensity score–weighted and propensity score–matched analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to evaluate the effect of severe fibrosis/cirrhosis. In addition, we performed exploratory analyses to determine the effectiveness of RFA and SBRT in clinically relevant patient subsets. Results Overall, 3,684 (92.6%) and 296 (7.4%) nonsurgically managed patients with stage I or II HCC received RFA or SBRT, respectively. After propensity matching, 5-year overall survival was 29.8% (95% CI, 24.5% to 35.3%) in the RFA group versus 19.3% (95% CI, 13.5% to 25.9%) in the SBRT group ( P < .001). Inverse probability–weighted analysis yielded similar results. The benefit of RFA was consistent across all subgroups examined and was robust to the effects of severe fibrosis/cirrhosis. Conclusion Our study suggests that treatment with RFA yields superior survival compared with SBRT for nonsurgically managed patients with stage I or II HCC. Even though our results are limited by the biases related to the retrospective study design, we believe that, in the absence of a randomized clinical trial, our findings should be considered when recommending local ablative therapy for localized unresectable HCC.

Abstract Expression of DLL3 was examined in additional tumor types, as it was found to be highly expressed in tumor-initiating cells (TIC) in small cell lung cancer (SCLC), where a DLL3-targeted antibody drug conjugate (ADC), rovalpituzumab tesirine (Rova-T; SC16LD6.5; Saunders et al. 2015 Sci Transl Med 7:302ra136)) exerted clinically meaningful anti-tumor effects in a phase I trial (Spigel et al. 2016 Lancet Oncology; In Press). DLL3 expression was profiled by qRT-PCR, ELISA and immunohistochemistry in multiple tumor types. Patient-derived xenografts (PDX) from melanoma and ovarian small cell carcinoma were established and used for efficacy studies to determine the ability of Rova-T to impact tumor growth and TIC frequency. DLL3 expression was seen in metastatic melanoma (55%), low grade gliomas (90%), glioblastoma (70%), medullary thyroid cancer (65%), carcinoids (33%), dispersed neuroendocrine tumors in the pancreas (9%), bladder (57%) and prostate (24%), testicular cancer (90%), and lung adenocarcinomas with neuroendocrine features (80%). Unlike SCLC, where DLL3 does not predict clinical outcome on standard therapies, DLL3 expression negatively correlates with overall survival in melanoma and small cell bladder cancer. In mice bearing DLL3 positive melanoma PDX, treatment with a single dose of Rova-T resulted in effective and durable responses (&gt;100 days), which correlated with a significant impact on TIC frequency. Similarly, in mice bearing DLL3-positive ovarian small cell PDX, a single dose of Rova-T resulted in effective and durable responses (&gt;100 days). Our results show that DLL3 is expressed in many neuroendocrine tumors (lung, ovarian, prostate, bladder, etc), metastatic melanoma, medullary thyroid cancer, low-grade gliomas and glioblastoma. Given pre-clinical results showing efficacy of Rova-T in melanoma and ovarian small cell carcinoma, as well as encouraging clinical data with Rova-T in patients with recurrent/refractory SCLC, clinical evaluation of Rova-T in DLL3-positive melanoma, glioblastoma, medullary thyroid cancer and other high-grade neuroendocrine carcinomas is warranted. A “basket” trial enrolling patients with DLL3-positive solid tumors is now recruiting patients (NCT02709889). Citation Format: Laura R. Saunders, Samuel A. Williams, Sheila Bheddah, Kumiko Isse, Sarah Fong, Marybeth A. Pysz, Himisha Beltran, Loredana Puca, Verena Sailer, Juan M. Mosquera, Yu Yin, Jiaoti Huang, Andrew J. Armstrong, Jorge Garcia, Cristina Magi-Galluzzi, Vadim Koshkin, Petros Grivas, Farhad Kosari, John Cheville, Justin C. Moser, Thomas J. Flotte, Thorvardur Halfdanarson, Aaron Mansfield, Konstantinos N. Leventakos, Julian R. Molina, Douglas W. Ball, Barry D. Nelkin, Jill E. Shea, Courtney L. Scaife, Scott J. Dylla. Expression of DLL3 in metastatic melanoma, glioblastoma and high-grade extrapulmonary neuroendocrine carcinomas as potential indications for rovalpituzumab tesirine (Rova-T; SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody drug conjugate (ADC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3093. doi:10.1158/1538-7445.AM2017-3093

791 Background: With the surge of drug development in the past decade, early phase clinical trials (EPCT) have gained value evaluating the potential benefits of new therapies. The inclusion/exclusion criteria in EPCT are usually rigorous and may exclude many patients (pts) commonly seen in clinical practice. Our objective was to identify the most common comorbidities excluded in EPCT for CRC. Methods: ClinicalTrials.gov was queried on December 1stof 2015. We reviewed the characteristics and eligibility criteria of 369 phase I/II interventional drug trials including: experimental arm therapy, location, and exclusion/inclusion criteria. Logistic regressions were completed and exclusion was studied as a binary variable. Results: Of the 369 trials, 68% were phase II and 32% phase I. 46% were conducted in the United States, 30% in Europe, 15% in Asia and 9% in other locations. 74 (20%) trials excluded pts > 70 years of age. 142 (39%) trials required creatinine levels < 1.5 mg/dl, liver enzymes (AST/ALT) < 2.5 and bilirubin < 1.5 of the upper limit of normal. Cytopenia was a significant exclusion factor: 147 (47%) trials required Hgb > 9 g/dl and 218 (59%) excluded pts with platelets < 100,000/dl. In terms of comorbidities, 98 (27%) trials excluded pts with heart failure (NYHA class 3/4), 74 (20%) with atrial fibrillation, 112 (31%) with any anticoagulation therapy and 155 (42%) with positive HIV. Trials located in the US were more likely to exclude pts with Hgb < 9g/dl (OR: 1.5, 95%CI: 1.1-2.3, p < 0.05), immunotherapy trials were more likely to exclude pts on any anticoagulation (OR:1.8, 95%CI: 1.2-2.8, p < 0.007) and targeted therapy trials were more likely to exclude pts with history of DVT/PE or cardiovascular diseases (OR: 3.4, 95%CI: 1.9-5.8, p < 0.0001; OR: 2.3, 95%CI: 1.3-3.8, p < 0.002, respectively). Conclusions: 20% of EPCTs on CRC excluded pts with advanced age, organ dysfunction and common comorbidities. Many of the EPCT reviewed were not inclusive of our aging oncology population who are more likely to have multiple comorbidities. Investigators should review whether sufficient justification exists for every exclusion criterion before their incorporation in future trial protocols.

593 Background: Cancer stem cells or stemness-high cancer cells are considered to be fundamentally important for resistance to therapy, recurrence and metastasis. Napabucasin, a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting Stat3-driven gene transcription. Preclinical studies suggest that napabucasin sensitizes heterogeneous cancer cells to chemotherapeutics and targeted agents. Methods: This study was performed to assess signs of anti-tumor activity of napabucasin in combination with FOLFIRI +/- Bev in CRC pts. Napabucasin was administered at 240 mg BID. FOLFIRI (5-FU 400 mg/m2 bolus with 2400 mg/m2, irinotecan 180 mg/m2, and leucovorin 400 mg/m2 infusion) +/- Bev 5 mg/kg was administered biweekly until disease progression or other discontinuation criterion. pSTAT3 status of archival tumor tissue was assayed by immunohistochemistry using the H-score with pSTAT3highdefined as ≥ 5% pSTAT3+ cancer cells and tumor stroma staining at ≥ 2+ intensity. Results: 63 CRC pts with an average of >2 prior therapy lines were enrolled. No pharmacokinetic interactions or dose-limiting toxicity was observed. Most common adverse events (AEs) included grade 1/2 diarrhea, nausea, vomiting and fatigue. 25 pts had grade 3 AEs, including diarrhea (14), fatigue (4), dehydration (2), electrolyte imbalance (4), nausea (1) and weight loss (1) resolved with dose reduction and supportive care. Among 63 pts enrolled who received RECIST evaluation, disease control (CR+PR+SD) was observed in 49 pts (86%) with an overall response (CR+PR) of 28% with 1 pt achieving CR. Clinical trial information: NCT02024607. Conclusions: This phase Ib/II study suggests napabucasin may sensitize chemorefractory CRC to FOLFIRI +/- Bev. Encouraging signs of synergistic activity between napabucasin and FOLFIRI was observed in CRC pts regardless of pSTAT3 status.[Table: see text]