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PUBLIC RELEASE DATE:
23-May-2014

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Contact: Vicky Agnew
vicky.agnew@yale.edu
203-785-7001
Yale University

Yale Cancer Center's tip sheet for the 50th Annual Meeting of ASCO May 30-June 3, 2014

The news items below are from oral presentations or poster sessions scheduled for the 50th annual ASCO conference.

Yale Cancer Center will have experts available to speak with the media before or during ASCO.

Survival, response duration, and activity by BRAF mutation (MT) status of nivolumab (NIVO, anti-PD-1, BMS-936558, ONO-4538) and ipilimumab (IPI) concurrent therapy in advanced melanoma (MEL). (LBA #9003)

Authors: Mario Sznol, Harriet M. Kluger, Margaret K. Callahan, Michael Andrew Postow, Ruth Ann Gordon, Neil Howard Segal, Naiyer A. Rizvi, Alexander M. Lesokhin, Michael B. Atkins, John M. Kirkwood, Matthew M. Burke, Amanda Ralabate, Angel L. Rivera, Stephanie Anne Kronenberg, Blessing Agunwamba, William Feely, Quan Hong, Suba Krishnan, Ashok Kumar Gupta, Jedd D. Wolchok; Yale Cancer Center, New Haven, CT; Memorial Sloan Kettering Cancer Center, New York, NY; Memorial Sloan-Kettering Cancer Center, New York, NY; Georgetown-Lombardi Comprehensive Cancer Center, Washington, DC; University of Pittsburgh Medical Center, Pittsburgh, PA; Bristol-Myers Squibb, Princeton, NJ The full, final text of this abstract will be posted online at 7:30 AM (EDT) on Monday, June 2.

Keywords: immune therapy; melanoma; anti-PD-1

Inhibition of PD-L1 by MPDL3280A and clinical activity in pts with metastatic urothelial bladder cancer (UBC). (#5011)

Authors: Thomas Powles, Nicholas J. Vogelzang, Gregg Daniel Fine, Joseph Paul Eder, Fadi S. Braiteh, Yohann Loriot, Cristina Cruz Zambrano, Joaquim Bellmunt, Howard A. Burris, Siew-leng Melinda Teng, Xiaodong Shen, Hartmut Koeppen, Priti S. Hegde, Daniel S. Chen, Daniel Peter Petrylak; Barts Cancer Institute, Queen Mary University Hospital of London, London, United Kingdom; University of Nevada School of Medicine and US Oncology/Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Genentech, Inc., South San Francisco, CA; Yale Cancer Center, New Haven, CT; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Gustave Roussy, Villejuif, France; Vall d'Hebron University Hospital, Barcelona, Spain; Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA; Sarah Cannon Research Institute, Nashville, TN; Genentech Inc., South San Francisco, CA

Metastatic UBC is associated with a poor prognosis and limited treatment options. PD-L1 expression is prevalent in this disease and may protect cancer cells from immune-mediated destruction by binding to its receptors PD-1 and B7.1. MPDL3280A is a human anti-PD-L1 mAb with an engineered Fc-domain designed for optimized efficacy and safety. MPDL3280A was well tolerated in this pretreated UBC population. 50% of pts treated responded to treatment. Responses were rapid and on-going. Biomarker analysis revealed pharmacodynamic markers, as well as markers of potential mechanisms of resistance to therapy. ***Updated results to be delivered at ASCO.

Keywords: immune therapy; bladder cancer; PD-L1; anti-PD-L1; phase I clinical trials

Lifestyle changes improve biomarkers associated with breast cancer recurrence and mortality – two studies

A pair of Yale Cancer Center interventional studies involving breast cancer survivors found that lifestyle changes in the form of healthy eating and regular exercise can decrease biomarkers related to breast cancer recurrence and mortality. Effect of weight loss intervention on inflammatory and metabolic markers in breast cancer survivors. The lifestyle, exercise, and nutrition (LEAN) study. (#1505)

Authors (all from Yale): Erikka Loftfield, MPH; Maura Harrigan, MS, RD, CSO; Fangyong Li, MPH, MS; Xiaopan Yao; Brenda Cartmel, PhD; Yang Zhou, MPH; Mary Playdon, MPH; Lingeng Lu, MD, PhD ; Tara Sanft, MD; Melinda Irwin, PhD, MPH

In this study, obese or overweight women were randomized into two groups — those who received weight loss and exercise counseling — and a usual care group that received a brochure about lifestyle changes. After six months, women in the weight loss counseling group experienced an approximate 30% decrease in C-reactive protein (CRP) levels compared with a minimal decrease in women randomized to the usual care group. CRP is a marker of chronic inflammation and higher CRP levels have been associated with a higher risk of breast cancer mortality. A dose-response effect was found in women randomized to weight loss counseling in that women who lost at least 5% body weight experienced an approximate 22% decrease in insulin, 38% decrease in leptin, and 55% decrease in CRP, compared to significantly less biomarker improvement in women randomized to weight loss who lost less than 5% body weight.

Effect of exercise on weight, body fat, and serum inflammatory biomarkers in breast cancer survivors with aromatase inhibitor arthralgias (joint pain): The hormones and physical exercise (HOPE) study. (#9356)

Authors: Melinda Irwin, PhD, MPH; Brenda Cartmel, PhD; Cary Gross, MD; Fangyong Li, MPH, MS; Xiaopan Yao; Martha Fiellin, MPH; Elizabeth Ercolano, PhD; Maura Harrigan, MS, RD, CSO; Yang Zhou, MPH; Tara Sanft, MD; Kathryn Schmitz, PhD; Dawn Hershman, MD; Jennifer Ligibel, MD

Yale University, New Haven, CT; University of Pennsylvania, Philadelphia, PA; Columbia University, New York, New York; Dana Farber Cancer Institute, Boston, MA.

The HOPE study looked at the effect of exercise on body weight, body fat, and inflammatory biomarkers in 121 women with joint pain from taking aromatase inhibitors (AI) as adjuvant therapy. Participants were randomized into two groups — those who participated in twice-weekly strength training and 2.5 hr/wk of moderate-intensive aerobic exercise — and those who did no exercise (control group). After 12 months, the study found that the exercise group experienced an approximate 3% weight and body fat loss, and 6% decrease in CRP levels compared to increases in the control group.

Previous findings from the HOPE study showed exercise improved AI-associated joint pain, but results from this analysis of favorable decreases in body weight, fat and CRP found these markers did not mediate the beneficial effect of exercise on AI joint pain. Further HOPE analyses will be conducted to determine the mechanism(s) of how exercise improves AI joint pain.

Keywords: breast cancer; recurrence; survivorship; biomarkers; obesity; weight loss; exercise; quality of life

Estimating the impact of screening on three decades of cervical cancer incidence. (#1518)

Authors: Daniel Xiao Yang, Pamela R. Soulos, Brigette Davis, Cary Gross, James B. Yu; Yale School of Medicine, New Haven, CT

Yale researchers found that cervical cancer screening via Pap smear over three decades (1976-2009) was associated with an estimated reduction of up to half a million cervical cancer cases of all stages, with rates of reduction significant for African-American women. After rising steadily from 1951-1981, the percentage of all adult women who received cervical cancer screening stabilized at 71.7% in 1982 to 73.8% in 2010. Overall, from 1976 to 2009, there was a significant decrease in the incidence of early stage cervical cancer, from 10.2 to 5.4 cases per 100,000 women (p < .001). Late stage disease incidence also decreased, from 5.2 to 3.7 cases per 100,000 women (p < .001). After adjusting for "pre-screening era" rates of cervical cancer, we estimate that Pap smears were associated with a reduction of between 105,000 to 492,000 cases of cervical cancer over the past three decades in the U.S. The combined incidence among black women decreased from 26.9 to 9.7 cases per 100,000 women (p < .001), a greater decline compared to that of white women (13.7 to 8.5 cases per 100,000, p < .001), and women of other races (16.0 to 7.4 cases per 100,000, p < .001). We estimate that a large number of early and late stage cervical cancers were prevented, and the racial disparity in cancer rates was reduced during an era of increased screening. Given disparate access to the HPV vaccine, it will be important to continuously assess national cervical cancer incidence to measure the additional benefit of the vaccine against the known benefit of screening, and to ensure equal access and outcomes for all women.

Keywords: cervical cancer; screening; women's health; cancer disparities; prevention; public health

A Phase 2 Trial of Prostate Specific Membrane Antigen Antibody Drug Conjugate (PSMA ADC) in Taxane-Refractory Metastatic Castration-Resistant Prostate Cancer (mCRPC) (#5023)

Authors: Daniel Peter Petrylak, David C. Smith, Leonard Joseph Appleman, Mark T. Fleming, Arif Hussain, Robert Dreicer, A. Oliver Sartor, Neal D. Shore, Nicholas J. Vogelzang, Hagop Youssoufian, Vincent A. DiPippo, Nancy Stambler, Kathleen Huang, Robert Joseph Israel; Yale University Medical Center, New Haven, CT; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; University of Pittsburgh Medical Center, Pittsburgh, PA; US Oncology Research; Virginia Oncology Associates, Hampton, VA; University of Maryland Cancer Center, Baltimore, MD; Cleveland Clinic, Cleveland, OH; Tulane University, New Orleans, LA; Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Progenics Pharmaceuticals, Inc., Tarrytown, NY

PSMA expression on prostate cancer cells provides a rationale for ADC therapy. PSMA is a clinically validated target. PSMA ADC is a fully human antibody to PSMA linked to the microtubule disrupting agent MMAE. It induces cell cycle arrest and apoptosis specifically in PSMA-positive cells. We have completed enrollment in a multicenter phase 2 trial of PSMA ADC in mCRPC pts progressing after taxane and antiandrogen.

PSMA ADC at 2.3 mg/kg was active and well tolerated in heavily pretreated mCRPC pts. Updated safety and secondary efficacy endpoints from the 2.3 and 2.5 mg/kg cohorts will be presented. These data warrant further evaluation in this population. A taxane-naïve cohort is ongoing. Clinical trial information.

Keywords: prostate cancer; psma; targeted therapy; antibody drug conjugates

Updated efficacy and safety of the ALK inhibitor AP26113 in patients with advanced malignancies, including ALK+ non-small cell lung cancer (NSCLC). (#8047)

Authors: Scott N. Gettinger, Lyudmila Bazhenova, Ravi Salgia, Corey J. Langer, Kathryn A. Gold, Rafael Rosell, Alice Tsang Shaw, Glen J. Weiss, Narayana I. Narasimhan, David J. Dorer, Victor M. Rivera, Tim Clackson, Frank G. Haluska, D. Ross Camidge; Yale University, New Haven, CT; UC San Diego Moores Cancer Center, La Jolla, CA; The University of Chicago, Chicago, IL; Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA; Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX; Catalan Institute of Oncology, Barcelona, Spain; Massachusetts General Hospital Cancer Center, Boston, MA; Cancer Treatment Centers of America, Goodyear, AZ; ARIAD Pharmaceuticals, Inc., Cambridge, MA; University of Colorado Cancer Center, Aurora, CO

AP26113 is a novel orally-active tyrosine kinase inhibitor with preclinical activity against ALK and all 9 clinically-identified crizotinib-resistant mutants tested. The Phase (Ph) 2 portion of a Ph1/2 single arm, multicenter study in pts with advanced malignancies is underway. We report updated safety for all treated pts and efficacy data for ALK+ NSCLC pts previously treated with crizotinib.

AP26113 has promising anti-tumor activity in pts with crizotinib-resistant ALK+ NSCLC, including pts with brain metastases. A randomized Ph2 trial evaluating 90 mg QD vs. 90mg QD escalating to 180mg QD in crizotinib-resistant ALK+ NSCLC will begin shortly.

Keywords: NSCLC; ALK inhibitor; advanced malignancies

Clinical significance of TILs subtypes in non-small cell lung cancer.(#8082)

Authors: Kurt A. Schalper, Jason Brown, Joseph Francis McLaughlin, Roy S. Herbst, David L. Rimm; Department of Pathology, Yale School of Medicine, New Haven, CT; Department of Medical Oncology, Yale University, New Haven, CT; Yale Cancer Center, New Haven, CT; Department of Pathology, Yale University School of Medicine, New Haven, CT

Tumor infiltrating lymphocytes (TILs) are associated with better outcome in diverse neoplasms including non–small cell lung cancer (NSCLC). TILs are usually determined using subjective semi-quantitative methods. Studies suggest that TILs subtypes have independent roles and their contribution to prognosis remains unknown. Here, we measured TILs subtypes in NSCLC using objective methods and determined their relationship with clinico-pathologic characteristics and survival.

Increased CD3 and CD8 positive TILs are independent prognostic factors in NSCLC. Despite the positive relationship between TILs subtypes, only CD8 and CD20 show association with adenocarcinoma histology. Objective measurement of TILs subpopulations could be useful to predict response or monitor the off-target effect of anti-cancer immunostimulatory therapies.

Keywords: NSCLC; tumor infiltrating lymphocytes (TILs)

Effect of pre-existing mental health comorbidities (MHC) on stage and timeliness of care of solid tumors in Veterans Affairs Connecticut Healthcare System (VACHS).(#6542)

Authors: Roxanne Jimmy Wadia, Xiaopan Yao, Yanhong Deng, Jia Li, Steve Maron, Donna Connery, Handan Gunduz-Bruce, Michal G. Rose; Yale-New Haven Hospital, New Haven, CT; Yale Center for Analytical Sciences, New Haven, CT; Yale School of Medicine, New Haven, CT; VA Connecticut Healthcare System, West Haven, CT; VA Administration Connecticut, West Haven, CT

Axis I MHC affects approximately 18% and 30% of the adult US and VA population, respectively. There are limited and conflicting data on the impact of MHC on stage and timeliness of cancer care. The purpose of this study was to compare stage and timeliness of care in colorectal (CR), urothelial (UR) and head/neck (HN) cancers among Veterans with and without MHC. Stage at diagnosis of CR, UR and HN cancers in VACHS did not differ between patients with and without Axis I MHC. The presence of MHC did not result in delays in care. Our data provides reassurance that within a healthcare system that provides integrated, comprehensive medical and psychiatric care, patients with Axis I MHC do not experience significant delays in cancer care. Keywords: veterans' health; mental health comorbidities; timeliness of care

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