Kaur, Judith S.

Abstract Lessons Learned Everolimus does not have sufficient activity to justify its use as single agent in metastatic melanoma. Patients treated with 10 mg per day dose were most likely to require dose reductions. Everolimus appeared to reduce the numbers of regulatory T cells in approximately half of the treated patients; unfortunately, these effects were not correlated with clinical outcomes. Background Everolimus (RAD-001) is an orally active rapamycin analogue shown in preclinical data to produce cytostatic cell inhibition, which may be potentially beneficial in treating melanoma. We conducted a phase II study to evaluate the efficacy and safety of everolimus in patients with unresectable metastatic melanoma (MM). Methods This study included two cohorts; cohort 1 received 30 mg of everolimus by mouth (PO) weekly, and cohort 2 was dosed with 10 mg of everolimus PO daily. The endpoints of the study were safety, 16-week progression-free survival (PFS), overall survival (OS), and measures of immunomodulatory/antiangiogenic properties with therapy. Tumor samples before therapy and at week 8 of treatment were analyzed. Peripheral blood plasma or mononuclear cell isolates collected prior to therapy and at weeks 8 and 16 and at time of tumor progression were analyzed for vascular endothelial growth factor and regulatory T-cell (Treg) measurements. Results A total of 53 patients were enrolled in cohort 1 (n = 24) and cohort 2 (n = 29). Only 2 patients of the first 20 patients enrolled in cohort 2 had treatment responses (25%; 95% confidence interval, 8.6%–49.1%); this result did not allow full accrual to cohort 2, as the study was terminated for futility. Median OS was 12.2 months for cohort 1 versus 8.1 months in cohort 2; no PFS advantage was seen in either group (2.1 months vs. 1.8 months). Dose-limiting toxicities included grade 4 myocardial ischemia (3.4%); grade 3 fatigue, mucositis, and hyperglycemia (10.3%); and anorexia and anemia (6.9%). Everolimus significantly reduced the number of Tregs in approximately half of the treated patients; however, these effects were not correlated with clinical outcomes. Conclusion Everolimus does not have sufficient single-agent activity in MM; however, we have identified evidence of biological activity to provide a potential rationale for future combination studies.

Alcohol drinking is an established risk factor for several malignancies, and it is a potentially modifiable risk factor for cancer. The Cancer Prevention Committee of the American Society of Clinical Oncology (ASCO) believes that a proactive stance by the Society to minimize excessive exposure to alcohol has important implications for cancer prevention. In addition, the role of alcohol drinking on outcomes in patients with cancer is in its formative stages, and ASCO can play a key role by generating a research agenda. Also, ASCO could provide needed leadership in the cancer community on this issue. In the issuance of this statement, ASCO joins a growing number of international organizations by establishing a platform to support effective public health strategies in this area. The goals of this statement are to: • Promote public education about the risks between alcohol abuse and certain types of cancer; • Support policy efforts to reduce the risk of cancer through evidence-based strategies that prevent excessive use of alcohol; • Provide education to oncology providers about the influence of excessive alcohol use and cancer risks and treatment complications, including clarification of conflicting evidence; and • Identify areas of needed research regarding the relationship between alcohol use and cancer risk and outcomes.

LBA1 Background: Five years of aromatase inhibitor (AI) therapy either as up-front treatment or after 2-5 years of tamoxifen has become the standard of care for postmenopausal women with hormone receptor positive early breast cancer. Extending treatment with an AI to 10 years may further reduce the risk of breast cancer recurrence. Methods: We conducted a double-blind, placebo-controlled trial (Canadian Cancer Trials Group MA.17R) to test the efficacy of extending AI treatment for an additional five years using letrozole. The primary endpoint was disease-free survival. Results: A total of 1,918 women with early stage breast cancer were enrolled (median follow-up 75 months, 6.3 years). A total of 165 disease-free survival (DFS) events (67 on letrozole and 98 on placebo) occurred, of which 42 versus 53 were distant recurrences on letrozole and placebo, respectively. There were 200 deaths (100 in each treatment group). The 5 year DFS was respectively 95% for patients receiving letrozole versus 91% for those on placebo (HR 0.66; P = 0.01) from a two-sided log-rank test stratified by nodal status, prior adjuvant chemotherapy, interval between last dose of AI therapy and randomization, and duration of prior tamoxifen at randomization. The 5 year overall survival was respectively 93% for subjects on letrozole and 94% on placebo with a HR of 0.97 (P = 0.83). The annual incidence rate of contralateral breast cancer was 0.21% for subjects on letrozole versus 0.49% on placebo (P = 0.007). Conclusions: Compared to 5 years of AI treatment as initial therapy or preceded by 2-5 years of tamoxifen, extending AI treatment to 10 years significantly improves disease-free survival. Further analyses will provide a comprehensive picture of toxicities and QOL. Clinical trial information: NCT00754845.

Abstract Background: It is documented that inequities in research participation by minority and underrepresented populations limits the progression of personalized medicine for cancer treatment for these groups. A lack of understanding essential information during the consent process and poor physician-patient communication have been noted as two overarching barriers to patients participating in translational, clinical and biospecimen research. To address these major patient barriers, we developed a plain language research literacy support (RLS) tool to improve the consent process and facilitate dialogue between physicians/research staff and patients. We describe the tool's iterative development process and testing of the developed culturally appropriate RLS tool. Methods: We tested the tool among: 1) patient participants ≥18 years of age, who were able to read and speak English from communities associated with five academic centers in the Midwest and Northeast United States; and 2) eligible recruiters who were employed at an academic center and actively recruiting patients into research. The development process for the RLS tool consisted of two phases: cognitive and beta testing. During cognitive testing, we solicited feedback from patient and recruiter participants about the content and format of the tool including low literacy language, pictures and recommendations for additional content. The tool consisted of concept cards to provide information to assist patients in making an informed decision about participating in research. During beta testing, a condensed version of the tool was tested to assess acceptability and change in knowledge about research participation. Results: Participants included 155 patients (52: cognitive testing phase; 103: beta testing phase) and 20 recruiter participants. Patient participants were mostly females (71%). Self-identified race of patients included: Whites (43%), African Americans (32%), Native Americans (20%), and other (6%). In addition, 23% of patient participants self-identified as Hispanic. During the cognitive testing phase, patient participants reported that the information was clearly laid out and the tool explained the different steps in the recruitment and enrollment process. Patient participants indicated they had learned new information related to randomization, standard of care, coded-information, and biobanking. Although some patient participants acknowledged the cards contained a great deal of information, most reported that the information was essential. Several participants suggested cards be tailored for the Native American population. Recruiters indicated that the cards provided useful information and would assist patients and research staff. During beta testing phase, 98% of participants agreed the information on the cards helped them understand clinical research. After reviewing the cards, 49% of patient participants reported that they would be very likely to participate in research and 32% reported being somewhat likely to participate in research. The majority (61%) of participants indicated that if invited to participate in a research study, they would prefer that the cards would be mailed to them in advance while 34% wanted to review the cards at their medical appointment. Half of the participants preferred accessing the cards on a computer if administered in a video format. Conclusion: The RLS tool was well received among patient and recruiter participants, making it a potentially valuable resource for enrollment of minority and underrepresented patients into health research. The next step will be to test the RLS tool for effectiveness in a randomized controlled trial. Citation Format: Erika E. de la Riva, Rodney Haring, Elisa M. Rodriguez, Evelyn Gonzalez, Mira Katz, Nikia Clark, Whitney Ann E. Henry, Rosa O. Ortiz, Barret J. Zimmermann, Marla L. Clayman, Deborah O. Erwin, Judith S. Kaur, Melissa A. Simon. Development and beta testing of a culturally appropriate research literacy support tool to increase research participation among minority and underrepresented populations. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr A11.

BACKGROUNDAmerican Indian and Alaska Native (AI/AN) breast cancer survivors experience disparities in breast cancer incidence and age‐adjusted mortality compared with non‐Hispanic white (NHW) breast cancer survivors. In addition, mortality‐to‐incidence rates indicate that AI/ANs continue to have the poorest survival from breast cancer compared with other racial groups. “Native American Cancer Education for Survivors” (NACES) is a cultural education and support intervention for AI/AN patients with cancer that collects data from voluntary participants through the NACES quality‐of‐life (QOL) survey regarding their cancer experience and survivor journey.METHODSData from the NACES QOL survey were analyzed to determine whether barriers accessing and during initial cancer treatment impacted QOL domains for AI/AN cancer survivors. Exploratory analyses of selected variables were conducted and were followed by Kruskal‐Wallis tests to determine whether these barriers influenced survivorship QOL for AI/AN breast cancer survivors.RESULTSAI/AN breast cancer survivors' social QOL was significantly affected by barriers to accessing cancer treatment. Many respondents experienced barriers, including a lack of cancer care at local clinics and the distance traveled to receive cancer care. During treatment, too much paperwork and having to wait too long in the clinic for cancer care were the most frequently reported barriers.CONCLUSIONSTreatment barriers influence AI/AN breast cancer survivors' social QOL. Mediating these barriers is crucial to ameliorating AI/AN survivors' disparities when accessing and completing cancer treatment and improving survivorship QOL. Cancer 2017;123:861–68. © 2016 American Cancer Society.