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Background: Biliary tract cancers, which arise from the intrahepatic or extrahepatic bile ducts and the gallbladder, generally have a poor prognosis and are rising in incidence worldwide. The standard-of-care treatment for advanced biliary tract cancer is chemotherapy with gemcitabine and cisplatin. Because most biliary tract cancers have an immune-suppressed microenvironment, immune checkpoint inhibitor monotherapy is associated with a low objective response rate. We aimed to assess whether adding the immune checkpoint inhibitor pembrolizumab to gemcitabine and cisplatin would improve outcomes compared with gemcitabine and cisplatin alone in patients with advanced biliary tract cancer. Methods: KEYNOTE-966 was a randomised, double-blind, placebo-controlled, phase 3 trial done at 175 medical centres globally. Eligible participants were aged 18 years or older; had previously untreated, unresectable, locally advanced or metastatic biliary tract cancer; had disease measurable per Response Evaluation Criteria in Solid Tumours version 1.1; and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Eligible participants were randomly assigned (1:1) to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks (maximum 35 cycles), in combination with gemcitabine (1000 mg/m2 intravenously on days 1 and 8 every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 intravenously on days 1 and 8 every 3 weeks; maximum 8 cycles). Randomisation was done using a central interactive voice-response system and stratified by geographical region, disease stage, and site of origin in block sizes of four. The primary endpoint of overall survival was evaluated in the intention-to-treat population. The secondary endpoint of safety was evaluated in the as-treated population. This study is registered at ClinicalTrials.gov, NCT04003636. Findings: Between Oct 4, 2019, and June 8, 2021, 1564 patients were screened for eligibility, 1069 of whom were randomly assigned to pembrolizumab plus gemcitabine and cisplatin (pembrolizumab group; n=533) or placebo plus gemcitabine and cisplatin (placebo group; n=536). Median study follow-up at final analysis was 25·6 months (IQR 21·7–30·4). Median overall survival was 12·7 months (95% CI 11·5–13·6) in the pembrolizumab group versus 10·9 months (9·9–11·6) in the placebo group (hazard ratio 0·83 [95% CI 0·72–0·95]; one-sided p=0·0034 [significance threshold, p=0·0200]). In the as-treated population, the maximum adverse event grade was 3 to 4 in 420 (79%) of 529 participants in the pembrolizumab group and 400 (75%) of 534 in the placebo group; 369 (70%) participants in the pembrolizumab group and 367 (69%) in the placebo group had treatment-related adverse events with a maximum grade of 3 to 4. 31 (6%) participants in the pembrolizumab group and 49 (9%) in the placebo group died due to adverse events, including eight (2%) in the pembrolizumab group and three (1%) in the placebo group who died due to treatment-related adverse events. Interpretation: Based on a statistically significant, clinically meaningful improvement in overall survival compared with gemcitabine and cisplatin without any new safety signals, pembrolizumab plus gemcitabine and cisplatin could be a new treatment option for patients with previously untreated metastatic or unresectable biliary tract cancer. Funding: Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

PURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430 ). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 ( nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 ( nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent ( nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine.

Background: Treatment of locally advanced pancreatic cancer (LAPC) remains a clinical challenge with a median survival of 16-18 months1. Control of local disease, beyond systemic therapy, is part of the treatment paradigm being investigated in this patient population. Double balloon mediated local delivery of intra-arterial gemcitabine (IAG) into the tumor has been demonstrated to be safe in this patient population2. TIGeR-PaC is an ongoing Phase III clinical trial comparing the efficacy of this approach compared to standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC. Methods: The trial is designed with an induction phase for all patients of upfront systemic chemotherapy and radiation prior to randomization to IAG or continuation of GN. ECOG 0-1 LAPC patients receive 3 cycles of GN and 1 cycle of radiation (SBRT, 33 Gy in 5 fractions). Following induction, patients with non-progressive disease are randomized to receive IAG (8 treatments bi-weekly for 16 weeks) or continuation of GN for 4 cycles over 16 weeks. After the 16 weeks of randomized therapy, patients with non-progressive disease receive continuation systemic therapy of GN or low-dose oral capecitabine, per investigator’s preference until disease progression and are followed for survival only. The primary endpoint is the overall survival (OS), and the study is powered at an 80% power to detect a hazard ratio of 0.6 between the two arms. It is assumed that the hazard functions are proportional only during the randomized treatment period, after which the two hazard functions become approximately identical during the continuing treatment period. The primary endpoint of OS for the two treatment arms will be compared using a 2-sided Wilcoxon test. The first interim analysis of the trial for the ITT population is performed after the 26th out of an expected 86 events have occurred in the trial (30%). Clinical Endpoint Analysis: The first interim analysis of the primary endpoint of OS was conducted on Feb 2nd, 2023. This was based on a data lock on survival status of all patients after the sponsor became aware that the 26th event in the trial occurred on Dec. 21st, 2022. As of that date, 45 patients had been randomized in the trial and the survival status of all 45 subjects was used as of the date for analysis. Of the 45 patients randomized, 23 were randomized to IAG and 22 to continuation of IV GN. There were equal number of primary events, 13, in each arm. The median survival in the control arm is 10 months, versus 16 months in the IAG arm. The p-values based on Wilcoxson non-proportional hazard ratio is 0.051 between the 2 arms. The study continues to accrue patients with a second interim analysis (after 52 events) expected at end of 2024. 1. Hammel P, Huguet F, van Laethem JL, et al. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib. JAMA. 2016;315(17):1844. 2. Rosemurgy AS, Ross SB, Vitulli PL, et al. Safety Study of Targeted and Localized Intra-Arterial Delivery of Gemcitabine in Patients with Locally Advanced Pancreatic Adenocarcinoma. J Pancreat Cancer. 2017;3(1):58-65. Citation Format: Michael Pishvaian, Amer Zureikat, Charles Lopez, Kenneth Meredith, Emmanuel Zervos, Hassan Hatoum, Ki Chung, Daniel J. Berg, Antonio Ucar, Ripal Gandhi, Reza Nazemzadeh, Parikh Nainesh, Paula Novelli, Brian Kouri, Christopher Laing, Brian Boone, Thor Johnson, Susan Bates, Karyn Goodman, Ramtin Agah. Targeted intra-arterial gemcitabine vs. continuation of IV gemcitabine plus nab-paclitaxel following Induction with sequential IV gemcitabine plus nab-paclitaxel and radiotherapy for unresectable locally advanced pancreatic cancer (TIGeR-PaC) - phase III trial interim analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT084.

Background: Pre-operative chemoradiation (CRT) followed by surgery for localized EGAC leads to a pathologic complete response (pCR) rate of 20%. Achievement of pCR is associated with improved overall survival (OS). Therefore, several studies have used IC before CRT to improve pCR rates but saw mixed results. We used a novel combination of FTD/TPI and oxaliplatin as IC before the standard CRT in localized EGAC with the primary objective of increasing the pCR rate. Methods: We enrolled patients (pts) in this open-label, single-arm, multicenter, phase II trial between Jan 2020 and Oct 2022. Pts with potentially resectable EGAC, adequate organ function, ECOG performance status of 0 -1, age Results: Of the 22 enrolled pts, 19 (86.4%) were male, and 20 (90.9%) were Caucasian. The median age was 61 years, and 12 (54.5%) had a primary disease at the gastroesophageal junction. Twenty (90.9%) pts had T3 disease, and 15 (68.2%) had node-positive disease by EUS. IC led to a 35% or more reduction in SUVmax in 60% of patients before CRT. At the time of data cutoff, 13 (59.1%) had surgery, 1 (4.5%) was awaiting surgery, 5 (22.7%) had progressive disease during the study, and 3 (13.6%) discontinued the study due to adverse events (AEs). Only 2 pts had pCRs, and an additional 4 had near pCRs. Since we could not meet our pre-defined pCR rate in stage 1, the study was closed due to futility. After a median follow-up of 15.8 months, 2-year OS and DFS were 43% and 41%, respectively. Nine (40.9%) had grade 3 or higher AEs. Nausea (59.1%) and fatigue (59.1%) were the most common treatment-related AEs; these were grade 1-2 events. The most common grade 3 or higher events were neutropenia (13.6%) and lymphopenia (9.1%). No febrile neutropenia was noted. Conclusion: IC with FTD/TPI and oxaliplatin before standard CRT failed to improve pCR in resectable EGAC, although it was reasonably well tolerated and showed activity. Ct DNA analysis is ongoing and will hopefully identify a select subgroup of pts who may benefit from this approach. Citation Format: Sarbajit Mukherjee, Sylvia Alarcon, Christos Fountzilas, Sarah Chatley, Renuka Iyer, Deepak Vadehra, Moshim Kukar, Kristopher Attwood, Anthony George, Alyson Brown, Chih-Yi Liao, Hassan Hatoum, Sagila George. Trifluridine/tipiracil (FTD/TPI) and oxaliplatin as induction chemotherapy (IC) in resectable esophageal and gastroesophageal junction adenocarcinoma (EGAC): Preliminary results from a phase II study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT146.

Objectives To compare the efficacy and safety of algenpantucel-L (HAPa; IND# 12311) immunotherapy combined with standard of care (SOC) chemotherapy and chemoradiation to SOC chemotherapy and chemoradiation therapy alone in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC). Summary background data To date, immunotherapy has not been shown to benefit patients with borderline resectable or locally advanced unresectable PDAC. HAPa is a cancer vaccine consisting of allogeneic pancreatic cancer cells engineered to express the murine α(1,3)GT gene. Methods A multicenter, phase 3, open label, randomized (1:1) trial of patients with borderline resectable or locally advanced unresectable PDAC. Patients received neoadjuvant SOC chemotherapy (FOLFIRINOX or gemcitabine/nab-paclitaxel) followed by chemoradiation (standard group) or the same standard neoadjuvant regimen combined with HAPa immunotherapy (experimental group). The primary outcome was overall survival. Results Between May 2013 and December 2015, 303 patients were randomized from 32 sites. Median (IQR) overall survival was 14.9 (12.2-17.8) months in the standard group (N=158) and 14.3 (12.6-16.3) months in the experimental group (N = 145) (hazard ratio [HR] 1.02, 95% CI 0.66-1.58; P = 0.98). Median progression-free survival was 13.4 months in the standard group and 12.4 months in the experimental group (HR 1.33, 95% CI 0.72-1.78; P = 0.59). Grade 3 or higher adverse events occurred in 105 of 140 patients (75%) in the standard group and in 115 of 142 patients (81%) in the experimental group (P > 0.05). Conclusions Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation. Trial registration ClinicalTrials.gov Identifier: NCT01836432.

PURPOSE The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCH) trial, the largest national precision oncology study to date (> 1,100 sites) of patients with relapsed or refractory malignancies, assigned patients to targeted therapy in parallel phase II studies based on tumor molecular alterations. The anti–programmed death receptor 1 inhibitor nivolumab previously showed activity in mismatch repair (MMR)–deficient colon cancer. We hypothesized that nivolumab would have activity in patients with MMR-deficient, noncolorectal tumors. PATIENTS AND METHODS Eligible patients with relapsed or refractory tumors, good end-organ function, and Eastern Cooperative Oncology Group performance status of ≤ 1 underwent tumor biopsy for centralized screening of molecular alterations. MMR deficiency was defined by complete loss of nuclear expression of MLH1 or MSH2 MMR gene products by immunohistochemistry (IHC). Patients with MMR-deficient colorectal cancer were excluded. Nivolumab, 3 mg/kg every 2 weeks (28-day cycles) and 480 mg every 4 weeks after cycle 4, was administered intravenously. Disease reassessment was performed every 2 cycles. The primary end point was RECIST 1.1 objective response rate (ORR). RESULTS Two percent of 4,902 screened patients had an MMR-deficient cancer by IHC. Forty-two evaluable patients were enrolled, with a median age of 60 years and a median of 3 prior therapies. The most common histologies were endometrioid endometrial adenocarcinoma (n = 13), prostate adenocarcinoma (n = 5), and uterine carcinosarcoma (n = 4). ORR was 36% (15 of 42 patients). An additional 21% of patients had stable disease. The estimated 6-, 12-, and 18-month progression-free survival rates were 51.3% (90% CI, 38.2% to 64.5%), 46.2% (90% CI, 33.1% to 59.3%), and 31.4% (90% CI, 18.7% to 44.2%), respectively. Median overall survival was 17.3 months. Toxicity was predominantly low grade. CONCLUSION A variety of refractory cancers (2.0% of those screened) had MMR deficiency as defined in NCI-MATCH. Nivolumab has promising activity in MMR-deficient noncolorectal cancers of a wide variety of histopathologic types.

TPS773 Background: Prognosis for locally advanced pancreatic cancer (LAPC) remains dismal even with advances in cancer therapy. Beyond systemic therapies, local disease control is important in these patients. Local double balloon mediated delivery of intra-arterial gemcitabine (IAG) was demonstrated to be safe in this patient population in a prior study1. TIGeR-PaC is an ongoing Phase-3 clinical trial comparing the efficacy of this approach compared to standard of care IV gemcitabine/nab-paclitaxel (GN) for patients with LAPC. Methods: The trial is designed with an induction phase of upfront systemic therapy prior to IAG. Patients with LAPC diagnosed within 6 weeks and ECOG 0-1, receive 3 cycles of GN and 1 cycle of radiation. The form of radiation was either IMRT, 50 Gy in 25 fractions, with concomitant capecitabine or SBRT, 33 Gy in 5 fractions (per site preference). Following induction, patients with non-progressive disease were randomized to receive IAG (8 treatments every two weeks for 16 weeks) or continuing therapy with 4 cycles of GN. After the 16 weeks of randomized therapy, the patients with non-progressive disease went on to continue systemic therapy (GN or capecitabine, per investigator’s preference) until disease progression and then followed for survival only. The primary endpoint is overall survival, and the study has an 80% power to detect a hazard ratio of 0.6 between the two arms. As of September 1st, 2022, 189 patients have been enrolled in the trial. In its initial design the trial expected a 35% drop out rate during the induction phase; however, two years into the trial the actual observed dropout rate was 53%. Beyond progression (22%), the key element of dropout rate was AE/SAE during radiation with IMRT/capecitabine (17%) vs. only 6% with SBRT. To increase accrual of randomized patients, the protocol and the statistical plan were modified to restrict the mode of radiation during induction to SBRT only starting December 2021. Since the modification of the protocol, the dropout rate during induction has decreased to 38%. As of this abstract, 43 patients have been randomized following induction with GN and SBRT. The rate of SAE during active treatment is not different between the 2 arms (20% in each arm), and the most common SAE is GI side effects in both arms. The protocol has a pre-planned interim analysis after 26 events, with 23 events at this writing we expect our first interim analysis later this year. 1. Rosemurgy AS, e al: J Pancreat Cancer. 2017;3(1):58-65. doi:10.1089/pancan.2017.0011. Clinical trial information: NCT03257033 .

713 Background: Locally advanced pancreatic cancer (LAPC) remains one of the deadliest cancers. Radiation is listed as a first line therapy option in treatment guidelines and remains a common treatment for this patient population primarily for local disease control and symptoms. Herein, we performed an exploratory analysis to compare the toxicity and efficacy between patients receiving either stereotactic body radiation therapy (SBRT) or intensity-modulated radiation therapy (IMRT) during the induction phase (prior to randomization) of a Phase 3 trial for localized intra-arterial gemcitabine therapy. Methods: As part of the TIGeR-PaC Phase 3 trial, patients with LAPC and an ECOG of 0-1 underwent an induction phase and were treated with 2 cycles of gemcitabine and nab-paclitaxel prior to receiving SBRT (n=59; 33Gy in 5 Fractions) or IMRT (n=75; 50Gy in 25 fractions) with concurrent PO capecitabine BID Monday-Friday. We performed Mann-Whitney analyses to compare mean percent changes in tumor size (imaging performed prior and 1-month after radiation) and CA 19-9 tumor markers. Adverse event (AE) incidence data during and 2 weeks after completion of the last fraction of radiation was used to compare toxicity via a contingency table. Results: A total of 134 patients across 22 sites (63 male/71 female; median age: 68.5 years) underwent radiation with no significant difference in baseline demographics between SBRT and IMRT patients. The decision for SBRT vs. IMRT was site-driven and not pre-specified by the protocol. Of these, 104 had analyzable imaging data, 50 SBRT and 54 IMRT, with a mean baseline tumor size of 4.3 cm and 4.0 cm (p=0.17), respectively. Pancreatic tumor location included head (n=63), body (n=36), or other (n=5). There was no statistical significance between the mean percent change of tumor size between SBRT (-13.3%) and IMRT (-10.8%; p=0.834). Both arms had similar RECIST partial response (approximately 18% of patients) after treatment. Patients with analyzable CA 19-9 tumor marker data (14 SBRT, 17 IMRT) showed no significant difference in percent change (mean, 9.8%±111%, -40.7%±40%; p=0.262). The SBRT subgroup had significantly less patients drop-out due to clinical deterioration (1 SBRT, 9 IMRT; p=0.025) and experience any AE (26 SBRT, 49 IMRT; p=0.014), gastrointestinal AE (10 SBRT, 33 IMRT; p

Purpose Notch signaling dysregulation is implicated in the development of pancreatic adenocarcinoma (PDAC). Tarextumab is a fully human IgG2 antibody that inhibits Notch2/3 receptors. Patients and methods Aphase 2, randomized, placebo-controlled, multicenter trial evaluated the activity of tarextumab in combination with nab-paclitaxel and gemcitabine in patients with metastatic PDAC. Patients were stratified based on ECOG performance score and Ca 19-9 level and randomized 1:1 to nab-paclitaxel, gemcitabine with either tarextumab or placebo. Based on preclinical and phase Ib results suggesting a positive correlation between Notch3 gene expression and tarextumab anti-tumor activity, patients were also divided into subgroups of low, intermediate, and high Notch3 gene expression. Primary endpoint was overall survival (OS) in all and in patients with the three Notch3 gene expression subgroups (≥25th, ≥50% and ≥75% percentiles); secondary end points included progression-free survival (PFS), 12-month OS, overall response rate (ORR), and safety and biomarker investigation. Results Median OS was 6.4 months in the tarextumab group vs 7.9 months in the placebo group (HR = 1.34 [95% CI = 0.95, 1.89], P = .0985). No difference observed in OS in the Notch3 gene expression subgroups. PFS in the tarextumab-treated group (3.7 months) was significantly shorter compared with the placebo group (5.5 months) (hazard ratio was 1.43 [95% CI = 1.01, 2.01]; P = .04). Grade 3 diarrhea and thrombocytopenia were more common in the tarextumab group. Conclusions The addition of tarextumab to nab-paclitaxel and gemcitabine did not improve OS, PFS, or ORR in first-line metastatic PDAC, and PFS was specifically statistically worse in the tarextumab-treated patients. Clinical trial registry no NCT01647828.

BACKGROUND: Pancreatic neuroendocrine tumors (panNETs) are a rare group of tumors that make up 2%–3% of pancreatic tumors. Recommended treatment for panNETs generally consists of resection for symptomatic or large asymptomatic tumors; however, optimal management for localized disease is still controversial, with conflicting recommendations in established guidelines. Our study aim is to compare surgical intervention versus active surveillance in nonmetastatic panNETs by size of primary tumor. MATERIALS AND METHODS: Using the National Cancer Database, we identified 2,004 patients diagnosed with localized well‐differentiated, nonfunctional panNETs (NF‐panNETs) between 2004 and 2015. Patients’ clinicopathologic characteristics, treatment modalities, and overall survival (OS) were analyzed using frequency statistics, chi‐square, and Kaplan‐Meier curves. The objective of the study is to assess the outcome of surgical resection versus nonoperative management in patients with panNETs with different tumor sizes. RESULTS: Tumor sizes were divided into three categories: 2 cm. The number of patients with tumor size 2 cm was 220 (11%), 794 (39.6%), and 990 (49.4%), respectively. Overall, 1,781 underwent surgical resection, whereas 223 patients did not. Median follow‐up was 25.9 months. After adjusting for covariates, surgical resection was associated with improved OS in patients with tumor size 1–2 cm (hazard ratio [HR] = 0.37) and >2c m (HR = 0.30) but not

Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine produced from the essential amino acid tryptophan. Serotonin’s role as a neurotransmitter in the central nervous system and a motility mediator in the gastrointestinal tract has been well defined, and its function in tumorigenesis in various cancers (gliomas, carcinoids, and carcinomas) is being studied. Many studies have shown a potential stimulatory effect of serotonin on cancer cell proliferation, invasion, dissemination, and tumor angiogenesis. Although the underlying mechanism is complex, it is proposed that serotonin levels in the tumor and its interaction with specific receptor subtypes are associated with disease progression. This review article describes serotonin’s role in cancer pathogenesis and the utility of the serotonin pathway as a potential therapeutic target in cancer treatment. Octreotide, an inhibitor of serotonin release, is used in well-differentiated neuroendocrine cancers, and the tryptophan hydroxylase (TPH) inhibitor, telotristat, is currently being investigated in clinical trials to treat patients with metastatic neuroendocrine tumors and advanced cholangiocarcinoma. Several in vitro studies have shown the anticancer effect of 5-HT receptor antagonists in various cancers such as prostate cancer, breast cancer, urinary bladder, colorectal cancer, carcinoid, and small-cell lung cancer. More in vivo studies are needed to assess serotonin’s role in cancer and its potential use as an anticancer therapeutic target. Serotonin is also being evaluated for its immunoregulatory properties, and studies have shown its potential anti-inflammatory effect. Therefore, it would be of interest to explore the combination of serotonin antagonists with immunotherapy in the future.

381 Background: There is no established treatment for locally advanced pancreatic cancer (LAPC), but by utilizing the regimens approved for metastatic pancreatic cancer, hope remains for rendering tumors resectable with chemotherapy. In this context, we looked at the resection rate in patients receiving gemcitabine plus nab-paclitaxel (Gem-Nab) in a prospective trial of patients with LAPC. Methods: TIGeR-PaC is an ongoing phase III clinical trial, studying the role of intra-arterial Gemcitabine (IA-Gem) in LAPC. The trial is designed with an induction phase where patients receive 3 cycles of Gem-Nab and a cycle of radiation after which they are randomized to IA-Gem or continuing with 4 cycles of Gem-Nab. We studied the resection rate in patients receiving Gem-Nab during induction who had subsequently continued receiving Gem-Nab post-randomization. Results: As of July 2020, 80 patients have been enrolled in the study. From this report, 30 patients were excluded because they had not completed induction and/or active treatment or were randomized to IA-Gem at the time of analysis. From the remaining 50 patients, 5 underwent resection for an overall resection rate of 10%. The median age for the total cohort was 67 years (range 47-83). Most of the resections were performed on the younger cohort of patients under 65 years (median age 60, range 47-65) in whom the resection rate was 4 out of 22 (18.2%). Conclusions: In the younger cohort of patients, TIGeR-PaC results are in line with the 15% resection rate in the LAPACT trial of patients with median age of 65 years, as reported by Phillip et al., 2020. In the TIGeR-PaC study the resection rate for LAPC treated with Gem-Nab was 10% overall, and 18.2% for younger patient population. These resection rates are comparable to the other reports for Gem-Nab and are similar to retrospective reports for the younger patients undergoing resection after treatment with FOLFIRINOX. Clinical trial information: NCT03257033.

399 Background: For patients with pancreatic cancer, tumor growth causing obstruction of the bile duct is a common, yet troubling occurrence, leading to potential serious complications including severe infections. A common technique to correct such an occurrence is the placement of a biliary stent. However, a biliary stent can cause a separate series of complications, especially for patients receiving chemotherapy. A current standard of care treatment for locally advanced pancreatic cancer is intravenous (IV) infusion of gemcitabine and nab-paclitaxel, with the prescribing information for these drugs noting that 5% of patients have experienced sepsis, with those having biliary stents potentially becoming fatal. Methods: In an on-going phase III clinical trial comparing standard of care IV gemcitabine and nab-paclitaxel versus intra-arterial delivery of gemcitabine directly to the tumor via a novel dual-occlusion balloon catheter, data from the cohort of 78 patients (total enrolled as of 1 June 2020) were analyzed for the incidence rate of sepsis among patients with and without biliary stents present. Data analyzed were limited to the initial four-month induction phase, in which patients were to receive two cycles of IV gemcitabine and nab-paclitaxel, one cycle of either IMRT or SBRT, and then one more cycle of IV gemcitabine and nab-paclitaxel. Results: Among the 78 patients, 12 had one episode of sepsis for an incidence rate of 15%. Of the 78 patients, 39 had a biliary stent placed and 9 experienced sepsis during induction (23%) compared to 2 patients among the 39 without a biliary stent present (5%; Chi-square = 4.99, p = 0.02). One additional patient with a biliary stent experienced urosepsis due to urinary tract infection, unrelated to the biliary stent. The majority of the septic events occurred after placement of the stent during the first cycle of chemotherapy (5 of 9 patients), with an average of 8.2 days passed after a dose of chemotherapy was infused to the septic event (range: 2 to 20 days). There was no relationship between ANC and the risk of sepsis. Among other covariates analyzed, age, gender, BMI, and a history of diabetes were not factors shown to affect the likelihood of a septic event. Among the 9 patients who had a septic event with a biliary stent, 2 were fatal, and 3 were withdrawn from the study due to complications from the septic event. Conclusions: These data suggest while the placement of a biliary stent may alleviate certain complications with biliary obstruction, combined with the immunosuppressive qualities of chemotherapy, the likelihood of sepsis increases, with incidence rates significantly greater than those previously reported in the drugs’ prescribing information or previous studies. The current practice of the insertion of the biliary stent potentially introduces flora during the procedure, resulting in potential infection later with administration of chemotherapy. Clinical trial information: NCT03257033.

Background: Pancreatic neoplasms consist of exocrine, endocrine and benign tumors. Exocrine pancreatic cancer is the fourth leading cause of cancer-related death in the US. Racial disparities in incidence, diagnosis, treatment, and outcomes have been evaluated in different types of tumors, but the data on pancreatic neoplasms are lacking. Our aim is to evaluate the racial disparities in clinical characteristics and survival of patients with pancreatic neoplasms. Methods: Using the National Cancer Database (NCDB), we identified 340,780 patients diagnosed with a pancreatic neoplasm between 2004 and 2015. Simple descriptive statistics were created for all covariates. Chi-square analysis was used to examine the distribution of demographic and clinicopathologic variables among different races. Survival analysis was done on patients with either death dates or follow-up dates, totaling 305,576 patients. Kaplan Meier survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. Races were grouped into White, Black, Hispanic, and others. The objective of the study is to assess racial disparities in clinical presentation, and to evaluate whether this influences the outcomes in patients with pancreatic neoplasms. Results: The median age at diagnosis was 69 (range 18-90) years and 50.6% were males. Carcinoma was the most common histology (81.3%), followed by other histology (9.6%), benign (5.4%) and neuroendocrine (3.7%) tumors. The percent of White, Black, Hispanic, and other race was 74.5, 11.3, 5.0, and 9.1%. Whites presented at more advanced ages compared to Blacks, Hispanics, and others (78.3, 68.6, 69.3, 76.3% were ≥60 years at diagnosis; p$63,000 HR=1.20 [95% CI 1.19-1.22]). Unadjusted analysis showed Blacks had a marginally higher hazard of death than Whites, HR=1.02 [95% CI 1.01-1.03]. However, after adjustment for age, sex, histology, grade, comorbidity score, income, education, and year of diagnosis, Blacks and Hispanics had a slightly better overall survival than Whites, HR=0.96 [95% CI 0.94-0.97] and 0.85 [95% CI 0.84-0.87]. Among patients with treatment information, time to first treatment was significantly longer among Blacks and Hispanics compared to Whites (4.4 and 3.2 days longer on average, p Conclusion: Our study provides evidence that various disparities exist across different races in pancreatic neoplasms. However, they did not lead to inferior outcomes in minorities. Our findings should be examined in other cohorts where more data about treatment are available. Citation Format: Hussein Assi, Michael Machiorlatti, Sara Vesely, Vipul Pareek, Hassan Hatoum, Sarbajit Mukherjee. Racial disparities in clinical characteristics and outcomes of patients with pancreatic neoplasms: An eleven-year analysis of the National Cancer Database (NCDB) [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C086.

4515 Background: The APACT trial was one of the largest and most geographically diverse trials of adjuvant chemotherapy for resected PC, allowing for comparison of outcomes by geographic region. In this analysis, we report updated overall survival (OS) results for the intent-to-treat (ITT) population and examine outcomes by geographic region. Methods: Treatment-naive patients with histologically confirmed PC, macroscopic complete resection, Eastern Cooperative Oncology Group performance status 0 or 1, and carbohydrate antigen 19-9 < 100 U/mL were eligible. Stratification factors were resection status (R0/R1) and lymph node status (positive/negative). Treatment was initiated ≤ 12 weeks postsurgery. Patients received nab-P 125 mg/m2 + Gem 1000 mg/m2 or Gem 1000 mg/m2 on days 1, 8, and 15 of six 28-day cycles. The primary endpoint was disease-free survival by independent review. Secondary endpoints were OS and safety. Results: The updated OS analysis (data cutoff date, January 2020) revealed a median OS of 41.8 months with nab-P + Gem compared with 37.7 months with Gem alone (hazard ratio [HR] 0.81; 95% CI, 0.68 - 0.97; nominal P = 0.047; Table). In each geographic region, the median OS with nab-P + Gem was numerically longer than with Gem alone. Conclusions: The updated OS analysis of the ITT population supports the previously reported trend favoring nab-P + Gem. The geographic regional analyses reveal numerically longer OS with nab-P + Gem vs Gem alone and variable outcomes by region; however, the differences do not support the trend observed in the ITT population, potentially due to limited sample sizes. Registration: EudraCT (2013-003398-91). Clinical trial information: NCT01964430 . [Table: see text]

TPS464 Background: Neoadjuvant chemoradiation (CRT) followed by surgery is a standard approach for localized EGAC. Despite multimodality treatment, 5-year overall survival (OS) is less than 50%, with pathologic complete response (pCR) rates of 20%. Achievement of pCR is associated with an improved OS. We propose to use a novel combination of FTD/TPI and oxaliplatin as IC. We hypothesize that IC before CRT will increase the pCR rate in localized EGAC. Methods: This is an open-label, multicenter phase II trial. Patients (pts) with potentially resectable loco-regional EGAC are eligible. Pts. should have adequate organ function, ECOG performance status of 0 –1, age < 76 years, and endoscopic ultrasound-determined node-positive disease with any T-stage, or T3-T4a with any N stage. Pts. with T4b or M1 disease will be excluded. Pts. will receive three cycles of IC with FTD/TPI and oxaliplatin. Based on the maximum tolerated dose (MTD) observed in a phase I trial, FTD/TPI will be administered 35 mg/m² BID, days 1–5 every 14 days, with a fixed dose of oxaliplatin 85 mg/m² (day 1). Pts will then undergo concurrent CRT (standard radiation dose of 5040 cGY will be utilized) with weekly Carboplatin (AUC 2) and Paclitaxel (50 mg/m2) for 6 weeks followed by surgery. Our primary objective is to evaluate the pCR rate. The secondary objectives include evaluation of 2-year disease-free survival (DFS), 2-year OS, and assessment of toxicities of the IC. As a correlative endpoint, circulating tumor DNA level will be correlated with disease recurrence and metabolic response on PET CT. Assuming a historic pCR rate of 20% with standard CRT, 41 pts (enrollment of up to 45 pts accounting for non-evaluable pts) are needed to show a 15% increase in pCR with IC with 80% power at one-sided significance level of α = 0.1. In stage 1, n1= 22 evaluable pts will be enrolled. If there is 5 or more pCRs, an additional n2= 19 pts will be enrolled in stage 2. If 12 or more pCRs are observed in the total n = 41 evaluable pts, then the proposed treatment regimen will be considered promising for further study. We anticipate accrual over a 2-year period from 3 sites. Clinical trial information: NCT04097028.

e22515 Background: Soft tissue sarcomas (STS) are heterogeneous solid tumors of mesenchymal cell origin, often difficult to manage. Local recurrence of extremity STS with surgery alone ranges from 5-20% with amputation ; 40% with wide excision. Neoadjuvant therapies are used to improve surgical outcomes. There is currently no recognized optimal neoadjuvant chemoradiation regimen prior to resection of STS. At our institution, we have piloted a neoadjuvant regimen of daily Cisplatin with infusional Adriamycin concurrent with radiation to assess its impact on surgical outcomes and tumor control. Methods: Patients diagnosed with STS of any site were treated neoadjuvantly with Cisplatin 6mg/m2 IV over 3-5 mins given 20 to 30 minutes before radiation (5 days) for 6 weeks. Adriamycin was given in the inpatient setting at 12.5 mg/m2 IV over 24 hours on days 1-4, weeks 1 and 4. The radiation dose was 54 Gy in 30 fractions. More than 50% of patients were treated with IMRT planning. Results: Since 2011, 12 STS patients were treated preoperatively with this regimen. Of these patients, 9 underwent surgery. Six of the 9 surgical patients received this neoadjuvant protocol followed by resection in the upfront setting. All of the 6 upfront patients had negative surgical margins; all of these patients had grade 3 tumors. Necrosis was reported based on the FNCLCC grading system. The average percent of necrosis was 96.3% (95% confidence interval 50.4%, 99.8%). Toxicity: Reported according to the RTOG/EORTC Radiation toxicity grading system. Of all patients, grade 1-2 skin toxicity predominated (75%). No grade 4 toxicity reported. Hematologic toxicity: Of all patients, grade 2-3 hematologic toxicity during neoadjuvant chemotherapy was reported in 83% of patients; grade 4 in 1 patient. No febrile neutropenia occurred. Post-operative complications: Seroma/hematoma formation was the most common post-operative complication in the surgical patients. No severely delayed healing was noted. Survival:Nine of 12 patients were dead (6 of 9 surgical patients) at the time of this analysis, all of metastatic disease. Mean time to DM 7.4 months. Mean OS 10 months. Conclusions: Our novel regimen achieved high necrosis rates, and all surgical patients achieved negative margin status. These factors are prognostic and correlate with local control. The predominant pattern of failure was distant. With its acceptable toxicity, this regimen of neoadjuvant Cisplatin, Adriamycin and radiation should be examined in a randomized fashion versus neoadjuvant radiation alone to determine the long term outcomes.

413 Background: Fibrolamellar carcinoma (FLC) is a very rare liver tumor, comprising only 1% of all primary liver tumors in the United Sates. There is no standard of care for unresectable disease. Current practices are based on small retrospective studies and case series. We aim to analyze the clinicopathologic factors and treatment modalities affecting overall survival (OS) in FLC. Methods: Using the National Cancer Data Base (NCDB), we identified 496 patients diagnosed with FLC between 2004 and 2015. Simple descriptive statistics were created for all covariates. Survival data was available on 461 patients. Kaplan Meier Survival analysis was used for unadjusted results, and Cox proportional hazards model was used for multivariable analysis. The objective of the study is to identify predictors of survival in FLC. Results: The median age at diagnosis was 32 (range 18-90) years. Fifty-six percent were males. Stage distribution included 114 (31.2%), 43 (11.8%), 89 (24.3%) and 120 (32.8%) patients for stages I, II, III and IV, respectively. Median follow-up was 24 months. Surgery of the primary site was performed on 282 (56.9%) of patients, 146 (51.2%) of which had regional lymph node dissection. Seventy (47.9%) patients had pN+ disease. Among patients with available serum alpha fetoprotein (AFP) data, 146 (42.5%) had abnormal AFP levels (> 20 ng/mL). Median OS by stage were 78.5, 87.2, 18.6, and 10.6 months for stages I, II, III, and IV, respectively. Multivariate analysis showed that age (HR 1.01, p < 0.0001), pN+ (HR 2.31, p = 0.0003), and abnormal AFP (HR 1.69, p = 0.0003) were negative predictors of survival. Among metastatic patients, 57 (11.4%) had metastatectomy. Metastatectomy improved overall survival in stage IV FLC, HR 0.51 (95% CI 0.29-0.89). Conclusions: Independent predictors of decreased OS in patients with FLC include age, pN+ and abnormal AFP. Metastatectomy improved OS. FLC is a rare disease entity that warrants further investigations to better delineate optimal treatment approaches.

Small cell lung cancer (SCLC) is one of many types rapidly growing malignant diseases, such as Burkitt's lymphoma and testicular germ cell cancers. At present, there is no reliable way to screen for SCLC, and imaging modalities tend to be delayed in detecting this type of cancer. The clinical presentation of acutely and rapidly growing SCLC can mimic those of pulmonary inflammatory or infectious disorders, and in some instances, this delays appropriate management and negatively affects patient outcome.

Background: Red blood cell distribution width (RDW) is a strong predictor of adverse outcomes in patients with heart failure, stable coronary artery disease, stroke and acute myocardial infarction. The aim of our study was to explore the predictive value of RDW on all-cause mortality in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Method: This observational study includes 619 NSTEMI patients, discharged from Staten Island University Hospital between September 2004 and December 2006. Patients were divided into equal RDW tertiles and survival was evaluated in each tertile. Result: Patients in the highest RDW tertile (RDW >14) had higher in-patient (7 vs. 1%) and 4-year (30 vs. 7%) mortality rates compared to those in the lowest tertile (RDW 2 = 34.64, p < 0.0001). After controlling for Global Registry of Acute Coronary Events risk profile scores and other confounding variables, the RDW adjusted hazard ratio for 4-year all-cause mortality increased by 1.10 for each one unit increase in RDW (confidence interval 1.004–1.213, p = 0.042). Conclusion: RDW is an independent predictor of all-cause long-term mortality in NSTEMI patients. Further studies are needed to clarify the mechanisms of this association between RDW and adverse outcomes in patients with coronary artery disease.

Adult T-cell leukemia/lymphoma (ATL) is resistant to chemotherapy and carries a dismal prognosis particularly for the acute and lymphoma subtypes. Promising results were obtained with the combination of zidovudine and interferon-alpha. Chronic ATL has a relatively better outcome, but poor long-term survival is noted when patients are managed with a watchful-waiting policy or with chemotherapy. In ATL cell lines, arsenic trioxide shuts off constitutive NF-κB activation and potentiates interferon-alpha apoptotic effects through proteasomal degradation of Tax. Clinically, arsenic/interferon therapy exhibits some efficacy in refractory aggressive ATL patients. These results prompted us to investigate the efficacy and safety of the combination of arsenic, interferon-alpha, and zidovudine in 10 newly diagnosed chronic ATL patients. An impressive 100% response rate was observed including 7 complete remissions, 2 complete remissions but with more than 5% circulating atypical lymphocytes, and 1 partial response. Responses were rapid and no relapse was noted. Side effects were moderate and mostly hematologic. In conclusion, treatment of chronic ATL with arsenic, interferon-alpha, and zidovudine is feasible and exhibits an impressive response rate with moderate toxicity. Long-term follow up will clarify whether this will translate to disease cure. Overall, these clinical results strengthen the concept of oncogene-targeted cancer therapy.

e15761 Background: Although the efficacy of neoadjuvant chemotherapy (NACT) in achieving resectability in locally advanced pancreatic cancer (LAPC) has been 20-31%, many cases remain unresectable. The aim of this study is to evaluate the efficacy of adding chemo radiotherapy (CRT) to achieve resectability in LAPC that remained unresectable after NACT. Methods: Between January 2008 and December 2016, 38 patients with LAPC (borderline resectable or unresectable pancreatic cancer, BRPC or URPC) received NACT and remained unresectable; subsequently, all patients received CRT in an attempt to achieve resectability with curative-intent. The primary objective of this retrospective single institution study is to assess resection rate (RR) in these patients. The secondary objective is to assess overall survival (OS). Results: A total of 38 patients (22 male, 16 female) who were identified as BRPC (50%) or URPC (50%) at presentation as defined by multidisciplinary tumor board using pancreatic protocol CT scan received NACT and remained unresectable. The median age was 64 (56-70.5) years. The primary site was head of pancreas in 66% versus other sites in 34% . The T-stage distribution was T1 (2.6%), T2 (2.6%), T3 (34.2%) and T4 (60.6%). N0 and N1 were 63.1% and 36.9% respectively. The types of NACT included FOFIRINOX (39.5%), Gemcitabine-based (58%) and unknown (2.5%). The median number of NACT cycles was 4 (2.25-4). All patients received subsequent CRT. Only the primary tumor was targeted with a median dose of 5040 (4950-5400) cGy and a median number of fractions 18(18-28). Chemo used concurrently with radiation was 5-FU (52.5%), Xeloda (39.5%), Gemcitabine (5.5%) and unknown (2.5%). Of note, 36.8 % patients achieved resectablity (14/38). The R0 and R1 resections were 11 (28.9%) and 3 (7.9%) respectively. 52.6% patients received adjuvant chemotherapy. The OS was 17 (6-24) months in the R0 group versus 8 (7-9) months in the R1 group. For the whole group, median OS was 11.5 (7-18.25) months. Conclusions: The addition of CRT to NACT in LAPC may improve resectability leading to an OS that approximates the OS in those patients who had upfront resectable disease.

279 Background: Tarextumab (TRXT), fully human IgG2 antibody inhibits signaling of Notch2/ 3 receptors. Tumor regression seen in Notch3 (N3) expressing pt-derived pancreatic cancer xenografts when TRXT combined with Nab-P+Gem. Phase 2, randomized, placebo-controlled trial conducted to evaluate efficacy, safety of combination in mPC. Methods: Pts randomized 1:1 to TRXT or placebo (PL). TRXT given IV at 15 mg/kg q 2wks (D 1, 15), nab-P 125 mg/m2, GEM 1000mg/m2 on D1, 8, 15 q 28 days. Tissue for N3 gene expression determination was required. Primary endpoints: overall survival (OS) in all and in 3 subgroups determined by Notch 3 gene expression. Secondary: safety, progression-free survival (PFS) and overall response rate (ORR). Results: N = 177 pts randomized. Performance status (0 or 1), CA19-9 stratum (0 – ULN, > ULN – 59ULN, ≥ 59ULN) balanced. Clinical trial information: NCT01647828. . Conclusions: Addition of TRXT to Nab-P+Gem did not improve OS in 1st line mPC. A potential detrimental effect on PFS and ORR was seen in subjects with N3 < 25%ile.[Table: see text]

Pemetrexed is a new-generation antifolate agent, which was approved in the last decade for treatment of nonsquamous nonsmall cell lung cancer and malignant pleural mesothelioma [1]. In July 2009, the US Food and Drug Administration approved the use of single-agent pemetrexed in maintenance therapy of nonsquamous nonsmall cell lung cancer after successful first-line treatment [1]. We report the first case of maintenance pemetrexed that caused digital ischaemic gangrene requiring amputation. A 65-year-old African-American female was diagnosed with stage 4 lung adenocarcinoma with distant pulmonary metastases. Her only comorbidities were hypercholesterolaemia and hypertension, both controlled with the use of a statin and angiotensin-converting enzyme inhibitor, respectively. She completed four cycles of carboplatin and pemetrexed, resulting in partial tumour response. Following this, she was started on maintenance pemetrexed at 500 mg m−2 every 3 weeks, and her disease remained stable. The patient presented to the emergency room after the 32nd cycle of maintenance pemetrexed, complaining of episodes of intense pain in the digits of her left hand for 1 week. The pain started 1 day after the 32nd pemetrexed cycle, was initially intermittent, and lasted from a few minutes to a few hours. Pain was most severe in the left fourth digit. She also complained of episodic numbness, swelling and blanching of all digits. She denied any systemic symptoms or smoking history. Examination showed mild blanching of all left-hand fingers, and worsening of pain/blanching on exposure to cold water. Blood parameters, including a complete blood count, metabolic panel, sedimentation rate, C-reactive protein and antinuclear antibodies, were normal. Imaging studies showed stability of lung cancer. Arterial Doppler ultrasound revealed normal upper extremity macrocirculation. Her symptoms were thought to be related to Raynaud's phenomenon induced by chemotherapy. She was advised to avoid cold and was prescribed a calcium channel blocker. The patient had two subsequent emergency room visits for the same complaints, when further tests, including cytoplasmic antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibodies, cryoglobulins, C3- and C4-complement and two-dimensional echocardiography were performed. None of these tests showed any abnormality. Meanwhile, the patient went on to receive the 33rd scheduled chemotherapy cycle, following which she experienced significant worsening of pain and developed swelling and cyanosis of the fingers of the left hand. On re-evaluation, black eschar formation was seen on the tip of left fourth digit. An emergent angiogram of the left upper extremity showed patent ulnar and radial vessels but poor perfusion in the distal digital arteries, most severe in the fourth digit. There was no evidence of thrombus, embolus or any focal area of stenosis. The plasma level of D-dimer was within the normal range, similar to the baseline level prior to the initiation of chemotherapy. Given the extent of occlusion and gangrene formation, her fourth digit was amputated. Pemetrexed infusions were stopped owing to known chemotherapy-induced endothelial dysfunction. Two months later, she also needed amputation of the left third digit due to ischaemia/gangrene. No further episodes of digital ischaemia or gangrene have occurred to date, over a follow-up period of 21 months. Off pemetrexed, the patient's lung cancer progressed after 10 months and she was started on daily erlotinib treatment. Her disease has since been stable, and no recurrent ischaemic symptoms have been experienced thus far. The onset of ischaemic symptoms in this patient was seen in association with prolonged pemetrexed infusion in the absence of other disorders. There was rapid progression from the initial pain symptoms to a gangrenous finger, and symptoms resolved after discontinuation of pemetrexed. Paraneoplastic syndrome is unlikely to be responsible for the patient's symptoms because the cancer was stable at the time of presentation. All these findings suggest that the patient's ischaemic symptoms were an adverse consequence of long-term pemetrexed treatment (and not Raynaud's phenomenon or paraneoplastic syndrome). We hereby draw the following conclusions: (i) pemetrexed-induced non-embolic occlusive arterial disease can mimic Raynaud's phenomenon in the initial stages; (ii) patients on maintenance pemetrexed chemotherapy who report persistent digital pain require special attention and thorough investigation; (iii) the time window from the beginning of pain to the development of a nonsalvageable gangrenous digit may be short; (iv) cumulative toxicity from multiple pemetrexed infusions may lead to severe endothelial dysfunction and limb-threatening gangrene; (v) this potential risk of long-term pemetrexed use should be discussed with patients who have a high predisposition for an impaired micro- or macrocirculation; and (vi) postmarketing surveillance of long-term pemetrexed (>30 cycles) use should be studied to determine a definitive causal relationship between prolonged pemetrexed use and peripheral arterial ischaemic disorders.

Background: Epidermal growth factor receptor (EGFR) mutation analysis is a standard approach for initial therapeutic decision in patients with metastatic adenocarcinoma of the lung (MAL). The feasibility of performing EGFR mutation testing using pleural fluid specimen is not well characterized. Objectives: The aim of this study is to report the percentage of patients eligible for EGFR mutation testing based on the percentage of malignant cells (PMCs) in the pleural fluid using the pyrosequencing method. Methods: From our database, we reviewed the clinical data of 61 patients with malignant pleural effusion (MPE) secondary to MAL. The PMCs were divided into 2 categories with a cutoff point of 10% (PMC1 is defined as ≤10% and PMC2 is defined as >10%). For the pyrosequencing method, only patients in the PMC2 group were eligible for EGFR mutation testing. Results: Of 61 patients with MPE secondary to MAL, 38 (62.3%) were in the PMC2 group, which represents the percentage of patients eligible for EGFR mutation testing. Of these 38 patients, 15 patients had the testing done on the MPE. Quantity was not sufficient for testing only in 1 patient. Therefore, in PMC2 patients group, the rate of successful EGFR mutation testing was 93% (14 of 15). The thoracentesis volume was not significantly different between PMC1 and PMC2. Conclusion: Performing EGFR mutation analysis on the MPE in patients with MAL is feasible in 62% of patients. The rate of successful testing on the eligible samples is 93%.

e20622 Background: Various randomized controlled trials (RCTs) have shown improved outcomes with addition of aprepitant to standard antiemetic treatment (SAT) in preventing CINV. We conducted a met...

Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.