Northfelt, Donald W.

79 Background: Novel mechanisms are needed to provide high quality oncologic clinical care and clinical trial access to underserved and minority populations (UMP). UMP are underrepresented in cancer clinical trials, thus limiting the generalizability of the research. As a National Cancer Institute-Comprehensive Cancer Center, Mayo Clinic has the responsibility to ensure that its cancer care reaches a diverse patient population. Mayo Clinic in Arizona developed a clinical oncology practice in collaboration with the US Indian Health Service at Phoenix Indian Medical Center (PIMC), in part to address these needs. The relationship between Mayo and PIMC is invaluable and serves a crucial need in the community. The Mayo consultants serve as staff physicians in the “Oncology Center of Excellence” at PIMC and see 100 – 200 tribal members annually with new diagnoses of cancer or blood disorders. Being onsite at PIMC allows Mayo consultants to integrate seamlessly into the wider PIMC practice. Methods: Descriptive demographic data from the MCA-PIMC clinical practice were obtained from the PIMC practice database 2008 - 2017. Enrollment of MCA-PIMC patients into MCA cancer clinical trials were prospectively enumerated. Results: Between the time period of 2008-2017, 356 breast cancer patients and 259 colorectal cancer patients were seen by Mayo Clinic oncologists and the PIMC nurse practitioner. During the period of 2016-2017, there were 13 clinical trial referrals from PIMC with 8 of those patients being enrolled in Mayo cancer clinical trials. Conclusions: High quality oncologic clinical care can be provided via unique collaborations between academic oncology program and UMP-focused care provider. This mechanism allows access to cancer clinical trial opportunities for UMP. Prior to the established partnership, there were no Native American patients referred to clinical trials from PIMC, showing the critical pathway that has been forged. Importantly, this is the only known program of its kind in the country. By imbedding the cancer provider in the community, we are able to build trust with the underserved community and create a pathway to a quality care and clinical research.

65 Background: We need better methods to understand the social determinants of health and integrate psychosocial and economic sequelae of cancer and its treatment into healthcare delivery for ethnoculturally diverse population. A Patient-Reported Outcomes Quality of Life (PROQOL) instrument has been developed to capture less commonly discussed patient concerns (Personal Relationships, Emotional health, Physical health, Cancer diagnosis and treatment, Money and Care planning) and improve patient-provider communication. We sought to adapt this instrument and pilot it in underserved, ethnically diverse solid tumor and hematological malignancies patients at Maricopa Integrated Health System (MIHS) in Phoenix, AZ. Methods: Two focus groups (FG) were conducted to understand patient perspectives of an adapted Spanish version of PROQOL. This version was then piloted among patients on active cancer treatment. Patients also completed a Linear Analog Scale Assessment (from 1-10) for quality of life (QOL) and its domains (higher scores indicate better QOL). Results: All participants in both FG (11/12 female) were Hispanics, with a median age of 53 years. Participants agreed that the domains covered in the PROQOL represented the most important psychosocial needs in their cancer continuum. No difficulty in understanding the individual domains or questions for delving deeper into each domain was noted. Median age of 34 pilot study participants (74% female) was 48 years, 79% were Hispanic, 10% were African Americans and median household income was $ 43,924 (range 23,002-98,382). 28/34 completed the Spanish version. Most common concerns were ‘Money’ (32%): difficulty paying medical bills and non-medical expenses and ‘Cancer Diagnosis, Treatment and Survivorship’ (32%): type of cancer and treatment concerns. Median overall QOL was 8 (range 3-10). Conclusions: PROQOL is feasible for systematic capture of patient concerns in underserved, ethnic minority cancer patients. A better understanding of these challenges can help design interventions to improve psychosocial and financial outcomes for the vulnerable groups and decrease disparities in care delivery.

TPS592 Background: Persistent cell proliferation (Ki67 > 10%) on tumor biopsies as early as 2-4 weeks (wks) on neo endocrine therapy (ET) identifies resistant tumors in ~20% patients (pts) with early stage ER+ HER2- BC who are at high risk of relapse. Palbo plus ET significantly improves progression free survival in pts with ET naïve or resistant advanced ER+ HER2- BC, and is being evaluated in the adjuvant setting. However, biomarkers predictive of palbo sensitivity are unknown. Ki67 analysis of serial tumor biopsies in the neo palbo and ana (NeoPalAna) trial demonstrated that 2 wks of palbo plus ana potently inhibited Ki67 and induced complete cell cycle arrest (CCCA, Ki67≤2.7%) in tumors with high Ki67 post 4 wks ana run-in. This study is therefore aimed to prospectively investigate the biological activity of palbo plus ana in ET resistant ER+ HER2- BC. Methods: The primary objective is to assess the rate of CCCA (central Ki67 ≤2.7%) after 2 wks of neo palbo and ana. Secondary objectives include analysis of tumor biopsies to explore response biomarkers. Key inclusions include women with clinical stage 2/3 ER+ HER2- BC, central Ki67 > 10% after ≥2 wks of any neo ET, adequate organ function. Key exclusions include prior CDK 4/6 inhibitor, treatment of BC except ET, concomitant use of strong CYP3A4 inhibitor. Pts receive palbo (125mg PO daily, days 1-21, 28-day cycle), ana (1 mg PO daily) and goserelin (if premenopausal). Pts with C1D15 Ki67 > 10% will discontinue study. If C1D15 Ki67 ≤10%, pt will receive 4 cycles of treatment, and additional 10-12 days of palbo if counts normalized within 3 wks post C4D28. Following surgery, pts are eligible for 2 years of adjuvant palbo. A sample size of 37 (stage 1, n = 12, stage 2 n = 25) by simon optimal two stage phase II design will be employed to assess whether the rate of CCCA is ≤5% vs ≥20% (90% power, alpha 0.1). Stage 2 will proceed if ≥1 had CCCA in stage 1. If ≤3 of 37 had CCCA, this regimen will be considered ineffective. The study is active and has enrolled 4 pts. Clinical trial information: NCT01723774.

1043 Background: In estrogen receptor (ER) positive MBC, mutations (e.g. ESR1), identified from tumor biopsies or cfDNA, confer resistance. The concordance between mutations observed in tumor and cfDNA and the implications for response to Z-endoxifen, a potent anti-estrogen, are unknown. Methods: We previously conducted a phase I trial of Z-endoxifen in endocrine refractory, ER positive MBC. Seven dose levels were considered ranging from 20 to 160 mg/day followed by expansion cohorts (EC) of 40, 80, and 100 mg/day. Pretreatment blood samples (all pts) and fresh tumor biopsies (EC) were collected prospectively. Tumor and cfDNA were evaluated by targeted NGS. Results: 41 pts (38 evaluable) were enrolled. Prior endocrine therapy included aromatase inhibitors (37/38, 97%), fulvestrant (22/38, 58%) and tamoxifen (26/38, 68%). Substantial endoxifen exposure without DLTs at doses above 80 mg/day led to a halt in dose escalation and opening of the EC. Overall clinical benefit (stable > 6 months [7 pts.] or partial response by RECIST criteria [3 pts.]) rate was 26.3% (95%CI: 13.4-43.1%). cfDNA was obtained from 36 pts and mutations were identified in 13 (36%) including ESR1 [ Y537N or D538G] (5), PIK3CA [ H1047R or E542K] (8), TP53 [ K132R, R248Q, R267Q, or H179Y] (4), AKT ( Q79K) (1), and KRAS ( G12D) (1). In 5 pts with cf ESR1 mutations, 4 had additional cfDNA mutations including PIK3CA (3), and TP53 (1). PFS was shorter in pts with cfDNA mutations relative to those without (median: 61 vs.132 days; log-rank p = 0.021). Discordance was observed between tumor and cfDNA mutations where 3/7 PIK3CA tumor mutations were detected by cfDNA, 1/2 TP53 tumor mutations were detected by cfDNA, and 0/1 AKT tumor mutations were detected by cfDNA. Conversely, 2 pts had cfDNA mutations (either ESR1, TP53 or AKT) undetected in tumor. Conclusions: The absence of cfDNA mutations in patients with endocrine resistant, MBC treated with Z-Endoxifen was associated with significantly longer PFS. Given the discordance between tumor and cfDNA sequence data, future studies must determine which approach maximizes prognosis and prediction of benefit for estrogen-targeted therapy. Clinical trial information: NCT01327781.