Metastatic Pancreas Cancer Research Articles

Abstract 2556: Enhanced expression of human cyclin G1 (CCNG1) gene in metastatic cancer, a novel biomarker in development for CCNG1 inhibitor therapy

Abstract Background: Metastatic cancer is associated with, hitherto, an invariably fatal outcome. DeltaRex-G, a CCNG1 inhibitor, has induced long term (9-12 year-) survivorship in patients with metastatic melanoma, sarcoma, lymphoma and cancer of pancreas and breast. Purpose: To evaluate CCNG1 expression in tumors as a novel biomarker for identification of patients who are likely to benefit from CCNG1 inhibitor therapy. Methods: RNA sequence analysis was used to compare CCNG1 expression in tumor (TCGA, N=9161) versus normal tissues (TGCA, N=678 and GTEx, N=7187) from 20 organ sites, and in primary vs metastatic melanoma (N=106 & 367 respectively). Using IHC staining, the significance of differences between the number of CCNG1+ and Ki-67+ cells in normal tissues vs tumors were evaluated using paired Student’s t test. Pearson’s coefficient of correlation was used to evaluate the relationship between the number of Ki-67+ vs CCNG1+ cells. Results: CCNG1 gene expression, by RNA sequence analysis, was significantly enhanced in melanoma, sarcoma, leukemia, and cancers of the lung, thyroid, brain, liver, prostate, testicle, head and neck, bladder, kidney, adrenal, cervix, and pancreas, compared to normal tissues (p = 0.006- 1.8E-58), and even greater, in metastatic vs primary melanoma. In a subset of melanoma tumors, there was overall positive correlation with progression/metastasis in both Ki67 and CCNG1 expression levels. Consistent with these findings, IHC showed significant differences when comparing CCNG1 nuclear staining percentages between analogous healthy and cancerous tissues (p = 0.002, df = 11). The nuclear staining percentages of CCNG1 and Ki-67 share a statistically significant, positive correlation (r = .936977, p < 0.00001). Further, in some patients, the level of CCNG1 expression by IHC fluctuated over time. Conclusion: Taken together, these data indicate that (1) CCNG1 expression, is frequently enhanced in cancerous tumors compared to their normal analogous counterparts, and (2) the level of CCNG1 expression may change over time, necessitating real time analysis in order to determine the optimal timing for CCNG1 inhibitor therapy. A Phase 2 basket study of DeltaRex-G cell cycle checkpoint inhibitor therapy is planned to correlate treatment outcome parameters with CCNG1 expression in patients’ tumors and circulating tumor cells. Citation Format: Erlinda M. Gordon, Christopher Szeto, Joshua R. Ravicz, Sandeep Reddy, Michael Morse, Sant Chawla, Frederick Hall. Enhanced expression of human cyclin G1 (CCNG1) gene in metastatic cancer, a novel biomarker in development for CCNG1 inhibitor therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2556.

BRCA1/2 and multigene panel testing among metastatic breast, pancreas, prostate, and ovarian cancer patients.

e13160 Background: Given the availability of targeted therapies such as PARP inhibitors, patients with metastatic breast, pancreas, prostate, and ovarian cancer are recommended to have germline genetic testing for hereditary cancer syndromes. Completion of genetic testing among this population is understudied. Methods: We performed a retrospective study of 548 patients with stage 4 breast, pancreas, prostate, and ovarian cancer at diagnosis from January 2013-December 2017 identified in the New York Presbyterian Hospital Tumor Registry at Columbia University Irving Medical Center. Data on socio-demographics, clinical factors, and genetic testing completion and results were collected from the medical record. We conducted descriptive statistics. Results: Our study population had a median age of 66 years (range, 23-97) at diagnosis; 61% female; 50% non-Hispanic white/22% Hispanic/15% non-Hispanic black/5% Asian/7% other; 33% private insurance/16% Medicaid/44% Medicare/7% unknown insurance. Primary cancer was 24% breast, 8% ovary, 61% pancreas, and 7% prostate. Only 38 patients were seen by a genetic counselor (7%) and only 50 (9%) had genetic testing performed. Among those who underwent germline testing, 92% had multigene panel testing (median number of genes tested 13.5, range 2-74). Pathogenic variants were detected in 6 patients (12%), of which 4 had a BRCA1/2 mutation, and 26% had a variant of uncertain significance (VUS). Conclusions: We found that only a small percentage of metastatic breast, pancreas, prostate, and ovarian cancer patients underwent genetic testing. Further research is necessary to identify the barriers to genetic testing uptake in metastatic cancer patients. BRCA1/2 and multigene panel testing has important implications in this patient population not only for treatment decisions, but also to increase cascade testing in unaffected family members who may be at risk for malignancy in the future.

Nab-paclitaxel in combination with gemcitabine for the treatment of metastatic pancreas cancer: the South Wales experience.

The prognosis of pancreatic cancer remains very poor, with a 5-year survival rate of around 3%. There has been little impact from various chemotherapy regimens on improving outcome for several decades. Gemcitabine has been the mainstay chemotherapy for around two decades with little improvement in overall survival (OS) for patients with advanced disease. However, more recently, there has been a paradigm shift in treatment options for these patients. Reported in 2011, combination therapy with FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, and fluorouracil) showed a long awaited but modest improvement in survival, but is reserved only for a small proportion of very fit patients due to concerns over its toxicities. In 2013, the landmark phase III international study MPACT demonstrated an improvement in OS with the combination of nab-paclitaxel and gemcitabine (GEMBRAX) for the treatment of patients more akin to the real-world population. In the United Kingdom (UK), it was first made widely available on the National Health Service (NHS) in Wales in September 2014 and only recently received a final positive appraisal by NICE (National Institute of Clinical Excellence) for England in 2017. In this paper, we present our data on the use of this treatment for patients in South Wales and compare real-life practical experience with the MPACT data and reflecting the impact of this paradigm shift.

Phase 2 trial of the IDO pathway inhibitor indoximod plus gemcitabine / nab-paclitaxel for the treatment of patients with metastatic pancreas cancer.

4015Background: The indoleamine 2,3-dioxygenase (IDO) pathway is a key counter-regulatory mechanism that is exploited by tumors to prevent and evade anti-tumor immunity. Inhibitors of the IDO pathw...

Effectiveness and tolerability of FOLFIRINOX regime in metastatic pancreas cancer disease

Effectiveness and tolerability of FOLFIRINOX regime in metastatic pancreas cancer disease

Neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, neutrophil–platelet score and prognostic nutritional index: do they have prognostic significance in metastatic pancreas cancer?

Introduction: We aimed to evaluate the prognostic significance of neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), neutrophil–platelet score (NPS) and prognostic nutritional index (PNI) as proinflammatory markers in metastatic pancreas cancer (MPC).Material and methods: A total of 146 MPC patients followed up at our center were evaluated retrospectively for clinicopathological characteristics and hematological ratios (NLR, PLR, NPS and PNI). PNI was calculated as (10 × serum albumin [g/dL]) + (0.005 × peripheral lymphocyte count [per mm³]). Log rank and Cox regression analysis were used.Results: Median age was 53 years (range: 22–78) with male predominance (73.3%). Liver (94.7%) was the most common site for metastasis. Half (53.4%) of the patients had ECOG-PS <2; 18% had cholestasis. Palliative chemotherapy predominantly gemcitabine was given to 86.3% of the patients. Clinical benefit rate was 58.2% and objective response rate (ORR) was 23%. Median overall survival (OS) and progression-free survival (PFS) were 6.3 months (95% CI: 5.2–7.8) and 4.9 months (95% CI: 3.6-6.1). Age (p = .003), ECOG-PS (p = .0001), palliative chemotherapy (p = .002), cholestasis (p = .001) and NLR (p = .001) were statistically significant but PLR (p = .062), NPS (p = .86) and PNI (p = .51) were not significant in univariate analysis. Age (HR 1.026, 95% CI: 1.007–1.045, p = .007), ECOG-PS (HR 0.299, 95% CI: 0.202–0.443, p = .0001), cholestasis (HR 0.541, 95% CI: 0.325–0.901, p = .01) and NLR (HR 1.076, 95% CI: 1.025–1.130, p = .003) were significant prognostic factors in multivariate analysis.Conclusions: Basal high NLR (>3), advanced age (>60 years), poor ECOG-PS (>2) and cholestasis were independent poor prognostic factors in MPC. However, PNI, NPS and PLR had no prognostic significance (p = .51, p = .86 and p = .062, respectively).

Chimeric antigen receptor (CAR) T and other T cell strategies for pancreas adenocarcinoma.

Treatments in metastatic pancreas cancer remain based in cytotoxic chemotherapy, and novel treatment strategies are needed. Building on the emerging role of T cell therapy in hematologic malignancies and our understanding of the underlying biology of pancreas cancer, research is growing in the role of T cell therapy for patients with solid tumors in general and more specifically patients with pancreas cancer. This review will focus on describing the biology of T cell therapy and its current applications in pancreas cancer.

Goals of care documentation in advanced cancer.

58 Background: Documenting goals of care (GOC) is integral to patient centered care, decision making and quality performance. Studies show patients value conversations about GOC after receiving a terminal diagnosis. Positive effects have been demonstrated for survival, quality of life, disease management and healthcare savings. The ASCO QOPI recommends documentation within 3 visits from diagnosis of metastatic cancer. For hospital inpatients, GOC are more often integrated into care planning, as admissions frequently reflect changes in illness trajectory, yet documentation remains poor. This Quality Improvement (QI) initiative aims to increase GOC documentation for ambulatory patients and referral rates to Palliative Medicine. Methods: A retrospective cohort receiving palliative chemotherapy for metastatic lung, pancreas, colorectal and breast cancers during 2010-2015 were identified from pharmacy records at a Canadian Regional Cancer Centre. Inclusion criteria required a minimum of 4 clinic visits post treatment. Clinical notes of Oncologists and Palliative Medicine Physicians were reviewed for GOC documentation and referrals to Palliative Medicine. Baseline data determined improvement target rates. A clinical practice QI initiative applied passive and active phases, beginning May 2016. Passive phase included the development of a guideline, documentation template and referral process. The active phase is the implementation process (ongoing). Results: A cohort included 456 patients with metastatic cancer, 63% lung cancer. Oncologists documented GOC in 6% (26/456) and referred 47% to Palliative Medicine. GOC rate was 48% post-referral. Improvement target rates were set at 40% and for referrals 70% by March 2017. Analysis during the passive phase showed Oncologists’ GOC documentations increased to 15%. Analysis of the active phase is ongoing and preliminary results will be presented. Conclusions: Low rates of GOC documentation and referrals to Palliative Medicine persist. The passive phase of engaging physicians in the QI development positively influenced GOC documentation. This QI initiative will inform the sustainability of GOC documentation, Palliative Medicine referrals and standardization of institutional guidelines.

SMK/SM88 toxicity, efficacy, and patient reported outcomes in metastatic pancreas cancer.

e14060 Background: SMK/SM-88 is a combination of novel tyrosine isomer ( TI) and 3 low dose repurposed agents that are generally recognized as safe for typical use. Its mechanism of action is based on the Warburg effect. It has previously been reported to have clinical benefit with little toxicity in a variety of cancers (J. Clin. Oncol. 2013 31: e22095). We now report on a subset of subjects with pancreas cancer. Methods: Retrospective chart review. Results: Subjects received all four SMK/SM-88 components orally and subcutaneously, consisting of a proprietary altered TI, CYP3a4 inducer, mTOR inhibitor and mitochondrial oxidative stress catalyst, five days per week for a period of six weeks (1 cycle). A total of 11 pancreatic cancers cases were identified. The average age was 63.2 (44-81), 36.4% (4/11) were female. Prior treatment included surgery only (n = 3); chemo only (n = 4); multi-modality therapy (n = 2) and unknown or none (n = 2). Duration on study regimen was 3-57 weeks (mean = 28.5). Clinical benefits documented for all subjects included: 1-3 points improvement in ECOG performance status; 1-5 point mean improvement on EORTC questionnaire (scale 1-7); weight gain (1-5 lbs.); and reduction in pain levels (1-9 points/10 scale) with cessation of all analgesics by the end of cycle 1 in 36% (4/11). Overall reduction in tumor size was seen in 27.3% (3/11) including one CR with PFS of at least 6 months duration, and 2 PRs with one known PFS of 15wks. 72.7% (8/11) had stable disease for 6-61wks. One patient had an overall survival of 23.3 months with no further treatment, and one had an overall survival of 43.2 months. All subjects developed hyperpigmentation. Overall, all subjects tolerated the SMK/SM-88 compounds well. No serious or unexpected adverse events related to the agent have been reported. Conclusions: SMK/SM-88 is a promising treatment for metastatic pancreatic cancer with no significant toxicity. Additional studies are on going in other cancers and confirmatory pancreas investigations are planned.

A murine model of micrometastatic pancreas cancer

Objective: Pancreas cancer (PC) maintains a high mortality rate due to early metastatic spread to the liver. We have developed a murine model of metastatic PC designed to monitor the progression of a single micrometastatic (mM) cell, and are able to characterize the changes in the liver microenvironment in the presence of single mM cells. Methods: The murine PC cell line KCKO was transfected to express both Green Fluorescent Protein (GFP) and B-Galactosidase (B-Gal). Mice underwent orthotopic pancreas tumor implantation with luciferase-labeled KCKO. Seven days later, the mice underwent a second stage surgery involving primary tumor resection, splenic injection of KCKO/GFP/B-Gal, followed by hemi-splenectomy. At varying time points thereafter (24, 48, & 72 hours) the mice were sacrificed and individual liver lobes were processed. Results: Β-Gal expressing mM single tumor cells can be seen in liver tissue sections by X-gal staining. Analysis of the liver tumor microenvironment (TME) at time points after splenic injection revealed an increase in myeloid cells by flow cytometry, immunofluorescence, and immunohistochemistry. There was an up regulation of tumor-promoting and immunosuppressive genes by RT-PCR. Using CCR2−/− mice, there was a noted decrease of the myeloid cell infiltrate and mM in the liver TME, reinforcing the importance of the mobilizing signal of the CCR2–CCL2 chemokine axis. Conclusion: We developed a mouse model to recapitulate early micrometastatic PC occurrence in the liver after primary tumor resection. We can use this model to assess the progression of single cell liver mM and associated changes in the liver TME.

Correlation of phase 2 trials (Ph2t) results with outcomes of phase 3 trials (Ph3t) of investigational agents (IA) in locally advanced and metastatic pancreas cancer (LAMPC).

227 Background: There has been minimal improvement in treatment outcomes in LAMPC. We examined results of Ph2t and Ph3t to better understand potential reasons in order to improve future trial design. Methods: We conducted a systematic review of published Ph2t and Ph3t (1978-2015) of first-line treatment for LAMPC. Data for baseline characteristics and best objective response rate (ORR) were compared. Where possible, we compared outcomes for IA tested in Ph2t with corresponding Ph3t. Results: We identified 149 Ph2t with 180 treatment arms comprising 7499 participants. Ph2t were predominantly single-arm (83%) or multi-arms with different IA doses or combinations (5%). Only 12% were randomized studies with concurrent control. The median sample size was 42 (range 8-133). The pooled ORR was 13.8% (95% CI 13.0%-14.6%) but there was substantial heterogeneity (range 0-60%, Pheterogeneity &lt; .001; I2= 75.9%). Although 56% of Ph2t concluded that IA should be considered for Ph3t, only 11% actually proceeded to Ph3t testing. Factors associated with Ph3t testing included absence of randomized design with concurrent control (12.2% vs 5.6%), higher proportion of performance status 0 patients (24.4% vs 21.7%), higher proportion of locally advanced disease only (23.4% vs 15.4%), and higher median ORR (22.0% vs 15.4%). Of 26% Ph2t that investigated novel biological IA, 92% had a potential predictive biomarker but only 1 trial was enriched for the biomarker. Only 8% of Ph2t with novel biological IA proceeded to Ph3t. ORR of IA tested in Ph2t correlated moderate poorly with ORR (r2 = 0.21) and 6 month progression-free survival rate (r2 = 0.26) in corresponding Ph3t. Only 3 IA in Ph3t demonstrated clinically meaningful improvements. Conclusions: Despite multiple Ph2t conducted over 4 decades, only 11% progressed to Ph3t, with 3 IA ultimately improving clinical outcomes. Ph2t results do not inform Phase 3 testing of IA. Potential reasons include patient heterogeneity, overly optimistic interpretation of Ph2t results, lack of concurrent control in Ph2t and ineffective agents. These issues should be addressed in order to improve success of future Ph3t in LAMPC.

Economic Evaluations of First-Line Chemotherapy Regimens for Pancreatic Cancer: A Critical Review.

Effect sizes of efficacy of first-line treatments for (metastatic) pancreas cancer are constrained, underscoring the need for evaluations of the efficacy-to-cost relationship. We critically review economic evaluations of first-line chemotherapy regimens for pancreatic cancer since the 1997 introduction of gemcitabine. We searched PubMed/MEDLINE and EMBASE (1997-2015), and the websites of health technology assessment agencies. Two authors independently reviewed economic studies for eligibility in this review; evaluated peer-reviewed, journal-published studies in terms of the Drummond Checklist; and critiqued the technical and scientific merit of all studies. Sixteen pharmacoeconomic evaluations were included: ten published in nine peer-reviewed journals and six on three websites. Six were on single-agent therapies and ten on combination therapies. Analyses conducted included cost-effectiveness (three studies), cost-utility (one study), or combined cost-effectiveness and cost-utility (12 studies). Studies diverged in results, mainly because of different assumptions, methods, inputs, and country-specific guidelines. The two most recent regimens, nanoparticle albumin-bound paclitaxel plus gemcitabine (NAB-P+GEM) and the combination of fluorouracil, oxaliplatin, leucovorin, and irinotecan (FOLFIRINOX), were evaluated in an indirect comparison, yielding a statistically similar benefit in overall survival but superior progression-free survival for FOLFIRINOX. NAB-P+GEM showed greater economic benefit over FOLFIRINOX. In conclusion, the divergence in results observed across studies is attributable to economic drivers that are specific to countries and their healthcare (financing) systems. No recommendations regarding the relative economic benefit of treatment regimens, general or country-specific, are made as the purpose of pharmacoeconomic analysis is to inform policy decision-making and clinical practice, not set policy or define clinical practice.

FOLFIRINOX for advanced pancreatic cancer: the Princess Margaret Cancer Centre experience.

Background:FOLFIRINOX has been shown to significantly increase both overall survival (OS) and progression-free survival (PFS) in metastatic pancreas cancer. There is limited data regarding the treatment of locally advanced pancreatic cancer. We present a retrospective study of patients with both locally advanced and metastatic pancreas cancer using FOLFIRINOX as first-line therapy in our centre.Methods:This is a retrospective review of patients treated with FOLFIRINOX for pancreatic cancer at Princess Margaret Cancer Centre, between December 2011 and July 2014. The primary objective was to evaluate the efficacy and safety of FOLFIRINOX when used with dose modifications.Results:One hundred two patients were identified; 66 metastatic and 36 locally advanced. Sixty-eight per cent of patients initiated treatment with a dose reduction. The median (95% CI) OS in the metastatic group was 13.1 (6.3–16.1) months with full dose and 12.9 (10.3–30.1) months with modified dose. The median (95% CI) OS in the locally advanced group was 11.1 (6.1–not reached) months with full dose and 23 (not reached–not reached) months with modified dose. The median (95% CI) PFS in the metastatic group was 6.2 (4.9–15.2) months with full dose and 8.7 (5.7–12.9) months with modified dose. The median (95% CI) PFS in the locally advanced group was 11.1 (3.1–not reached) months with full dose and 10.4 (6.8–not reached) months with modified dose. Grade 3/4 haematologic adverse events were observed in 43% of patients. Grade 3/4 non-haematologic adverse events were observed in 28% of patients. Patient well-being significantly improved from baseline to cycle 4 (P=0.002).Conclusions:Efficacy was achievable with dose-modified FOLFIRINOX in daily setting. The safety of FOLFIRINOX remains a concern with a high rate of grades 3 and 4 neutropaenia despite dose reduction.

Phase 2 trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreas cancer: Interim analysis.

3020 Background: Indoleamine 2,3 dioxygenase (IDO) is a tryptophan-catabolizing enzyme that plays a key role in the normal regulation of peripheral immune tolerance. Tumors also employ this mechanism. In cancer, IDO can either be expressed by the tumor cells themselves, or induced indirectly in host antigen presenting cells. In these settings, IDO mediates an acquired immune tolerance, allowing evasion of immune mediated destruction. Indoximod is a broad IDO pathway inhibitor, shown to potentially interfere with multiple targets. The combination of gemcitabine and nab-paclitaxel is a current SOC for metastatic pancreas cancer. Pre-clinical models have demonstrated synergy between IDO inhibition with indoximod and chemotherapy. The Phase 1 results demonstrated safety of the combination and a promising preliminary objective response rate. Additionally, a delay in the occurrence of the observed responses and the durability of the observed responses suggested an immune mediated mechanism. Methods: Patients are treated with indoximod (1200mg BID continuous dosing) in combination with gemcitabine / nab-paclitaxel (1000mg/m2 / 125mg/m2 q week x3 per 4 week cycle) in continuous 4 weeks cycles. Eligible patients have treatment naïve metastatic pancreatic cancer or 1st line salvage therapy after previous resection and adjuvant therapy. Treatment continues until disease progression or toxicity. Primary endpoint is overall survival. Secondary endpoints include response rate and progression free survival. Target enrollment is 80 patients in Phase 2. Results: At this interim analysis, 30 patients to date have been enrolled in Phase 1 / 2 and completed protocol treatment at least through imaging at the end of cycle 2. Of these, 11 (37%) have demonstrated an objective response by RECIST criteria including one patient with a confirmed complete response. One adverse event of immunological significance (colitis) was observed and required study withdrawl. Conclusions: The combination of indoximod and gemcitabine / nab-paclitaxel continues to demonstrate a promising objective response rate. Updated results will be presented. Clinical trial information: NCT02077881.

Weibull and exponential proportional hazard modelling for optimizing economic evaluations of cancer treatments: FOLFIRINOX (FFX) vs gemcitabine (GEM) in metastatic pancreas cancer (mPC).

e15704Background: Classical pharmacoeconomic analysis methods may prove insufficient for the economic evaluation of novel cancer treatments, esp. in advanced/metastatic setting as it is important to calculate a reliable and credible estimation of the total cost and outcomes. The application of different parametric models may impact economic evaluation estimates. Access to individual patient data from randomized controlled (RCT) trials is limited, hence digitization software is used to reproduce published Kaplan-Meier (K-M) curves and estimate distribution parameters. We compared the application of Weibull and exponential proportion hazard models to economic evaluation studies for FFX v. GEM in mPC. Methods: Weibull and exponential regressions were applied to progression-free (PFS) and overall (OS) survival data from digitization to derive the lambda and gamma parameters for Weibull and exponential models. Curves were estimated for FFX OS and PFS. Model selection was based on the value of R2and residual su...

Cost description of chemotherapy regimens for the treatment of metastatic pancreas cancer.

Multiple chemotherapy regimens are available for the treatment of metastatic pancreas cancer (mPCA). Choice of regimen is based on the patient's performance status and toxicity profile of the regimen. The objective of this study was to analyze the costs of first-line regimens to further aid in decision-making and develop a platform upon which to assess value. We calculated the monthly cost for individual standard regimens (gemcitabine, gemcitabine/nab-paclitaxel, gemcitabine/erlotinib and FOLFIRINOX) and the overall treatment cost for a course of therapy based on the median progression-free survival achieved in published studies. In addition to cost of drugs, we included administration costs and costs of toxicities (including growth factor support, blood product transfusion and hospitalization for toxicities). Costs for administration and management of adverse events were based on Medicare reimbursement rates for hospital and physician services. Drug costs were based on Medicare average sale prices (all 2014 US$). The monthly costs for gemcitabine, FOLFIRINOX, gemcitabine/erlotinib and gemcitabine/nab-paclitaxel were $1363, $7234, $8007 and $12,221, respectively. The overall treatment costs for a course of the same regimens based on median PFS were $5043, $46,298, $51,004 and $67,216, respectively. The choice of chemotherapy regimen for mPCA should be based on tolerability and efficacy of the regimen individualized to patient's performance status. Healthcare systems have finite resources; thus, there is increasing emphasis on metrics to define value in health care when outcomes of therapy are similar or produce marked differences in value. These data provide useful financial information to incorporate into the decision-making process.

Results of the phase Ib portion of a phase I/II trial of the indoleamine 2,3-dioxygenase pathway (IDO) inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreatic cancer.

452 Background: IDO is a tryptophan-catabolizing enzyme that plays a key role in the normal regulation of peripheral immune tolerance. Tumors also employ this mechanism to induce a state of immunosuppression. In cancer, IDO mediates an acquired immune tolerance towards tumors, allowing evasion of immune mediated destruction. Indoximod is a broad IDO pathway inhibitor, as it has been shown to potentially interfere with multiple targets within the IDO pathway. Pre-clinical models have demonstrated synergy between indoximod and chemotherapy. The combination of gemcitabine (Gem) and nab-paclitaxel (Nab) is a current SOC for first line treatment of metastatic pancreas cancer. This trial is designed to determine the potential for benefit of combination therapy with indoximod and Gem / Nab for to patients with metastatic pancreatic cancer. Methods: Indoximod was escalated (600mg/1000mg/1200mg PO twice daily continuous dosing) in combination with Gem / Nab (1000mg/m2 / 125mg/m2 q week x 3 per 4 week cycle) in a 3+3 design. Patients were first line metastatic pancreatic cancer or minimum 6 months from adjuvant chemo and / or radiation following previous resection. Treatment continues until progression or toxicity. Primary endpoints for Phase 1 include safety, toxicity, and determination of a Phase 2 dose. The prospective collection of tumor samples for exploration of biomarkers is built into the trial. Results: 15 patients were required to successfully dose escalate the Phase 1 study to 1200 mg twice daily. Two patients were replaced in the lowest dose cohort after rapid deterioration due to underlying disease during the regimen limiting toxicity (RLT) window. One RLT was observed during the study (ascites Grade 3) at the highest dose cohort. The most common AE’s (all Grade 1 or 2) occurring in ≥ 4 subjects, regardless of attribution, were nausea, fatigue, peripheral edema, peripheral neuropathy, alopecia. Conclusions: Indoximod and Gem / Nab were well tolerated in a clinical trial setting. The Phase 2 dose was set at 1200 mg twice daily and Phase 2 enrollment (target 80 patients) is ongoing. Updated results will be presented. Clinical trial information: NCT02077881.

Prognosis, Treatment Benefit and Goals of Care: What do Oncologists Discuss with Patients who have Incurable Cancer?

AimsDocumentation of advance directives among patients with terminal cancer is known to be poor. Here we describe documentation of prognosis, treatment benefit and goals of care discussions in outpatients with advanced cancer. Materials and methodsAll patients receiving first-line palliative chemotherapy for metastatic pancreas or lung cancers during 2010–2013 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes from medical oncology were reviewed to identify documentation of discussions regarding prognosis, treatment benefit and goals of care. Differences between groups were tested using the chi-squared test. ResultsIn total, 222 patients were included: 80% (177/222) with lung cancer and 20% (45/222) with pancreas cancer. Medical oncology notes documented discussion of prognosis in 64% (142/222), palliative intent of therapy in 82% (182/222), magnitude of treatment benefit in 29% (64/222) and goals of care in 4% (9/222) of patients. An estimate of survival was documented in 36% (79/222) of cases. Across medical oncology providers there was substantial variation in the frequency of discussing prognosis (range 33–90%, P < 0.001), treatment intent (range 55–100%, P < 0.001) and goals of care (range 0–17%, P = 0.034). In total, 41% (93/222) of patients were seen by palliative care; substantial medical oncology provider variation was observed (range 27–58%, P = 0.020). Referral rates to palliative care did not increase over time (41–44%, P = 0.250). ConclusionsIn this cohort of ambulatory patients with an estimated life expectancy of 1 year or less, medical oncology documentation of prognosis, treatment benefit and goals of care was poor. Less than half the patients were seen by palliative care. Initiatives to improve documentation and referral to palliative care are needed.

Highlights from Recent Cancer Literature

Highlights from Recent Cancer Literature

2292 The prognostic significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and prognostic nutritional index in metastatic pancreas cancer

2292 The prognostic significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and prognostic nutritional index in metastatic pancreas cancer