Elizabeth Claire Dees

Prospective validation of a 21-gene expression assay in breast cancer

BACKGROUND Prior studies with the use of a prospective-retrospective design including archival tumor samples have shown that gene-expression assays provide clinically useful prognostic information. However, a prospectively conducted study in a uniformly treated population provides the highest level of evidence supporting the clinical validity and usefulness of a biomarker. METHODS We performed a prospective trial involving women with hormone-receptor-positive, human epidermal growth factor receptor type 2 (HER2)-negative, axillary node-negative breast cancer with tumors of 1.1 to 5.0 cm in the greatest dimension (or 0.6 to 1.0 cm in the greatest dimension and intermediate or high tumor grade) who met established guidelines for the consideration of adjuvant chemotherapy on the basis of clinicopathologic features. A reverse-transcriptase-polymerase-chain-reaction assay of 21 genes was performed on the paraffin-embedded tumor tissue, and the results were used to calculate a score indicating the risk of breast-cancer recurrence; patients were assigned to receive endocrine therapy without chemotherapy if they had a recurrence score of 0 to 10, indicating a very low risk of recurrence (on a scale of 0 to 100, with higher scores indicating a greater risk of recurrence). RESULTS Of the 10,253 eligible women enrolled, 1626 women (15.9%) who had a recurrence score of 0 to 10 were assigned to receive endocrine therapy alone without chemotherapy. At 5 years, in this patient population, the rate of invasive disease-free survival was 93.8% (95% confidence interval [CI], 92.4 to 94.9), the rate of freedom from recurrence of breast cancer at a distant site was 99.3% (95% CI, 98.7 to 99.6), the rate of freedom from recurrence of breast cancer at a distant or local-regional site was 98.7% (95% CI, 97.9 to 99.2), and the rate of overall survival was 98.0% (95% CI, 97.1 to 98.6). CONCLUSIONS Among patients with hormone-receptor-positive, HER2-negative, axillary node-negative breast cancer who met established guidelines for the recommendation of adjuvant chemotherapy on the basis of clinicopathologic features, those with tumors that had a favorable gene-expression profile had very low rates of recurrence at 5 years with endocrine therapy alone. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00310180.).

Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer

BACKGROUND The recurrence score based on the 21‐gene breast cancer assay predicts chemotherapy benefit if it is high and a low risk of recurrence in the absence of chemotherapy if it is low; however, there is uncertainty about the benefit of chemotherapy for most patients, who have a midrange score. METHODS We performed a prospective trial involving 10,273 women with hormone‐receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative breast cancer. Of the 9719 eligible patients with follow‐up information, 6711 (69%) had a midrange recurrence score of 11 to 25 and were randomly assigned to receive either chemoendocrine therapy or endocrine therapy alone. The trial was designed to show noninferiority of endocrine therapy alone for invasive disease–free survival (defined as freedom from invasive disease recurrence, second primary cancer, or death). RESULTS Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive disease–free survival (hazard ratio for invasive disease recurrence, second primary cancer, or death [endocrine vs. chemoendocrine therapy], 1.08; 95% confidence interval, 0.94 to 1.24; P=0.26). At 9 years, the two treatment groups had similar rates of invasive disease–free survival (83.3% in the endocrine‐therapy group and 84.3% in the chemoendocrine‐therapy group), freedom from disease recurrence at a distant site (94.5% and 95.0%) or at a distant or local–regional site (92.2% and 92.9%), and overall survival (93.9% and 93.8%). The chemotherapy benefit for invasive disease–free survival varied with the combination of recurrence score and age (P=0.004), with some benefit of chemotherapy found in women 50 years of age or younger with a recurrence score of 16 to 25. CONCLUSIONS Adjuvant endocrine therapy and chemoendocrine therapy had similar efficacy in women with hormone‐receptor–positive, HER2‐negative, axillary node–negative breast cancer who had a midrange 21‐gene recurrence score, although some benefit of chemotherapy was found in some women 50 years of age or younger. (Funded by the National Cancer Institute and others; TAILORx ClinicalTrials.gov number, NCT00310180.)

TBCRC 003: Phase II trial of trastuzumab (T) and lapatinib (L) in patients (pts) with HER2+ metastatic breast cancer (MBC).

527 Background: In heavily pre-treated pts, L+T is associated with improved outcomes compared to L alone (Blackwell et al, 2009). We evaluated the safety and efficacy of L+T in pts with 0-2 prior lines of chemotherapy (CT) for HER2+ MBC. We also explored mechanisms of resistance and predictors of response to anti-HER2 therapy. METHODS Pts with measurable, HER2+ MBC were eligible. Cohort 1: No prior T, L, or CT for MBC, and > 1 yr from adjuvant T, if received. Cohort 2: 1-2 prior lines of CT for MBC, including T, or relapse within 1 yr of adjuvant T. Pts received L 1,000 mg QD + T (2 mg/kg weekly or 6 mg/kg Q3W). Baseline (BL) research biopsy was required. FDG-PET/CT was performed at BL, Wk 1, and Wk 8. Circulating tumor cells and plasma were collected at BL, Wk 4, and off-study. Staging studies were done at BL and every 2 cycles (1 cycle = 4 wks). The primary endpoint was objective response rate (ORR) by RECIST 1.0. The study was designed to distinguish between ORR 25% vs. 45% in Cohort 1 (>/= 5/17 pts to enter 2nd stage; 14 responses in 36 evaluable (eval) pts needed to be promising) and between ORR 10% vs. 25% in Cohort 2 (>/=3/22 pts to enter 2nd stage; responses in 8/40 pts needed to be promising). Secondary endpoints included clinical benefit rate (CBR; CR+PR+SD >/= 6 months), toxicity, and radiologic/biomarker correlates. RESULTS Enrollment was completed 10/28/2010 (Cohort 1, n=40; Cohort 2, n=47). 14 pts in Cohort 1 remain on protocol therapy. In Cohort 2, all pts have come off study; median number of cycles was 6 (range 1-18). Of the 1st 36 eval pts in Cohort 1, confirmed objective responses were observed in 41.7% (95% CI 23.0%-67.1%; 3 CR, 12 PR; 4 unconfirmed PR). Of the 1st 40 eval pts in Cohort 2, confirmed ORR was 25% (95% CI 11.2%-45.6%; 0 CR, 10 PR; 2 unconfirmed PR). CBR was 47.2% (95% CI 30.4%-64.5%) and 40% (95% CI 24.9%-56.7%), respectively. Grade 3/4 treatment-related toxicities were uncommon (grade 3 diarrhea, 7%; all others < 3%). No biopsy-related SAEs were reported. CONCLUSIONS L+T is an active regimen in HER2+ MBC. The study met its pre-specified primary endpoint in each cohort. Updated efficacy data will be presented. Imaging and tissue-based correlative analyses are underway.

Recurrence score and clinicopathologic characteristics of TAILORx participants by race and ethnicity.

36 Background: Black race is associated with worse outcomes in localized breast cancer. We evaluated the characteristics of patients enrolled in the Trial Assigning Individualized Options for Treatment (TAILORx) by race and ethnicity. METHODS The analysis included 10,071 evaluable patients with Recurrence Score (RS) data. Eligibility criteria included: (1) T1-2, N0 disease, (2) estrogen receptor (ER) and/or progesterone receptor (PR) positive disease that was also HER2/neu negative, (3) age 75 years or younger and medically appropriate for adjuvant systemic chemotherapy. RESULTS The study population included 8,501 whites (84%), 722 blacks (7%), 423 Asians (4%), and the remainder other/unknown race. With regard to ethnicity, 7,916 were nonHispanic (79%), 919 were Hispanic (9%), and 1,236 were of unreported ethnicity (12%). There was no significant difference in RS distribution (p = 0.14), median RS (17 vs. 17), and mean RS (19.6 vs. 18.4) in blacks compared with nonblacks. There was likewise no difference in Hispanic vs. nonHispanic ethnicity for RS distribution (p = 0.53), median RS (17 vs. 17), and mean RS (18.6 vs. 18.4). Blacks were significantly more likely to be younger (39% vs. 30% < 50 years), have larger tumors (37% vs. 31% > 2 cm), poor histologic grade (25% vs. 17%), and PR-negative disease (14% vs. 10%) (Chi square test p < 0.05). Hispanic women were also significantly younger (39% vs. 30% < 50 years), and demonstrated marginal but statistically significant differences in tumor size (65% vs. 69% > 2 cm), histologic grade (20% vs. 18% poor), and PR expression (12% vs. 10% negative) (Chi square test < 0.05). In 974 patients with information on body mass index (BMI), there was no correlation between BMI and RS (r = -0.04). BMI was higher for blacks than whites (medians 31.6 vs. 28.9, p = 0.02, Wilcoxon test), but not in Hispanics. CONCLUSIONS In patients selected for participation in TAILORx there were no significant differences in RS by race, ethnicity, and BMI. Black and Hispanic patients were significantly younger, and blacks had tumors that were larger and more likely to be associated with poor grade. CLINICAL TRIAL INFORMATION NCT00310180.

Abstract P4-13-25: Abemaciclib, an inhibitor of CDK4 and CDK6, combined with endocrine and HER2-targeted therapies for women with metastatic breast cancer

Background: Abemaciclib, a small molecule inhibitor of CDK4 and CDK6, induces G1 cell cycle arrest in Rb-proficient human cancers.1 The clinical safety profile of abemaciclib enables continuous oral dosing to achieve sustained target inhibition, resulting in single-agent antitumor activity against multiple human cancers. The drug also reaches relevant concentrations in the central nervous system and, in patients taking the drug orally, can be detected in the cerebrospinal fluid.2 For women with previously treated hormone receptor positive (HR+) metastatic breast cancer (MBC), abemaciclib as a single agent achieved a six-month clinical benefit rate of 61.1% and an objective response rate of 33.3%.3 Clinical trials investigating abemaciclib combined with fulvestrant4 or aromatase inhibitors5 have led to randomized Phase 3 studies for women with HR+ breast cancer.6,7 Methods: This Phase 1b study (NCT02057133) with multiple cohorts evaluates safety and tolerability of abemaciclib combined with endocrine or HER2-targeted therapies for MBC. Secondary objectives include pharmacokinetics (PK) and antitumor activity of abemaciclib when given in combination with other therapies. Cohorts were opened to enrollment sequentially. Patients with HR+ HER2 negative MBC received abemaciclib orally every 12 hours (Q12H) in combination with the following standard therapies daily until progression: letrozole (Part A), anastrozole (Part B), tamoxifen (Part C), exemestane (Part D), or exemestane plus everolimus (Part E). Patients with HER2 positive MBC received abemaciclib orally Q12H in combination with trastuzumab every 21 days until progression (Part F). Adverse events (AEs) were graded by NCI CTCAE v4.0 and tumor response was assessed radiographically using RECIST v1.1. Results: Abemaciclib has been combined with multiple targeted therapies for the treatment of women with MBC. We previously reported safety and early efficacy results for the combinations of abemaciclib with letrozole, anastrozole, tamoxifen, exemestane, and exemestane plus everolimus.5 Due to limited follow-up at that time, the efficacy results were not mature. Safety, PK, and efficacy results with approximately 6 months of additional follow-up will be reported across all parts of the study. The most common treatment-emergent AEs include effects on the gastrointestinal and hematopoietic systems. Consistent with previously reported results for both single-agent abemaciclib and the combination of abemaciclib with fulvestrant, tumor responses have been observed among women receiving abemaciclib in combination with targeted therapies for MBC. Conclusions: This study for women with MBC demonstrates the potential for abemaciclib to be combined with therapies targeting specific signaling pathways. References:1Gelbert et al. Invest New Drugs. 2014;32(5):825-37. 2Shapiro et al. J Clin Oncol 31, 2013 (suppl; abstr 2500). 3Tolaney et al. SABCS 2014: Abstract 763. 4Patnaik et al. J Clin Oncol 32:5s, 2014 (suppl; abstr 534). 5Tolaney et al. J Clin Oncol 33, 2015 (suppl; abstr 522). 6Llombart et al. SABCS 2014: OT1-1-07 (MONARCH 2, NCT02107703). 7Goetz et al. J Clin Oncol 33, 2015 (suppl; abstr TPS624) (MONARCH 3, NCT02246621). Citation Format: Goetz MP, Beeram M, Beck T, Conlin AK, Dees EC, Dickler MN, Helsten TL, Conkling PR, Edenfield WJ, Richards DA, Turner PK, Cai N, Chan EM, Pant S, Becerra CH, Kalinsky K, Puhalla SL, Rexer BN, Burris HA, Tolaney SM. Abemaciclib, an inhibitor of CDK4 and CDK6, combined with endocrine and HER2-targeted therapies for women with metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-25.

Informed Consent and Decision Making Among Participants in Novel-Design Phase I Oncology Trials

BACKGROUND Although phase I clinical trials are the gateway to progress in cancer therapies, this setting poses ethical challenges to ensure that patients provide consent free from misunderstandings of therapeutic intent or unrealistic expectations of benefit. The design of phase I oncology trials has evolved rapidly over time and today includes more targeted agents and combinations of experimental drugs with standard drugs, which may further complicate how patients understand phase I research participation. METHODS We conducted semistructured interviews regarding motivations, decision making, and understanding of trial purpose nested within a phase I clinical trial of a novel PI3kinase inhibitor combined with a standard oral chemotherapy in 18 participants. RESULTS Fewer than half of patients correctly identified the safety and dosing objectives. The inclusion of a targeted agent was attractive to participants and was perceived as an indicator of less toxic or more efficacious therapy, with less appreciation for added risks. The significance of a cellular drug target, without a known predictive biomarker of response, was unclear to patients. The inclusion of a standard drug in the regimen attracted patients with more treatment options than traditional first-in-human participants. Patients frequently expressed a realistic understanding of prognosis and uncertainty of benefit, but simultaneous hopes for extraordinary outcomes. CONCLUSION Novel phase I oncology trial designs may attract patients with less constrained treatment options, but the inclusion of targeted drugs and combinations including standard chemotherapies is likely to complicate understanding of safety and dosing objectives and likelihood of personal benefit for purposes of informed consent.

Aurora A Functional Single Nucleotide Polymorphism (SNP) Correlates With Clinical Outcome in Patients With Advanced Solid Tumors Treated With Alisertib, an Investigational Aurora A Kinase Inhibitor

Background Alisertib (MLN8237) is an investigational, oral, selective Aurora A kinase inhibitor. Aurora A contains two functional single nucleotide polymorphisms (SNPs; codon 31 [F/I] and codon 57 [V/I]) that lead to functional changes. This study investigated the prognostic and predictive significance of these SNPs. Methods This study evaluated associations between Aurora A SNPs and overall survival (OS) in The Cancer Genome Atlas (TCGA) database. The Aurora A SNPs were also evaluated as predictive biomarkers for clinical outcomes to alisertib in two phase 2 studies (NCT01045421 and NCT01091428). Aurora A SNP genotyping was obtained from 85 patients with advanced solid tumors receiving single-agent alisertib and 122 patients with advanced recurrent ovarian cancer treated with alisertib plus weekly paclitaxel (n = 62) or paclitaxel alone (n = 60). Whole blood was collected prior to treatment and genotypes were analyzed by PCR. Findings TCGA data suggested prognostic significance for codon 57 SNP; solid tumor patients with VV and VI alleles had significantly reduced OS versus those with II alleles (HR 1.9 [VI] and 1.8 [VV]; p < 0.0001). In NCT01045421, patients carrying the VV alleles at codon 57 (n = 53, 62%) had significantly longer progression-free survival (PFS) than patients carrying IV or II alleles (n = 32, 38%; HR 0.5; p = 0.0195). In NCT01091428, patients with the VV alleles at codon 57 who received alisertib plus paclitaxel (n = 47, 39%) had a trend towards improved PFS (7.5 months) vs paclitaxel alone (n = 32, 26%; 3.8 months; HR 0.618; p = 0.0593). In the paclitaxel alone arm, patients with the VV alleles had reduced PFS vs modified intent-to-treat (mITT) patients (3.8 vs 5.1 months), consistent with the TCGA study identifying the VV alleles as a poor prognostic biomarker. No significant associations were identified for codon 31 SNP from the same data set. Interpretation These findings suggest that Aurora A SNP at codon 57 may predict disease outcome and response to alisertib in patients with solid tumors. Further investigation is warranted.

Abstract PD3-5: Whole exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients with or without prior trastuzumab (T): A correlative analysis of TBCRC003

Background: Although the spectrum of genomic alterations in primary, treatment-naive breast tumors has been described, the genomic landscape of HER2+ MBC remains underexplored. Furthermore, tumor genomic alterations that arise after progression on anti-HER2 therapy are largely unknown. Methods: We prospectively collected metastatic tumor biopsies from patients (pts) enrolled on TBCRC003 (NCT00470704), a phase II study evaluating the combination of lapatinib (L) and T in pts with HER2+ MBC who had varying degrees of prior T exposure. We performed WES on baseline metastatic biopsies and normal DNA from 57 pts. In 36 pts, we also performed WES on pre-treatment primary tumors. Tumors were analyzed for point mutations, insertions/deletions, and copy number alterations. Results: Total accrual was 116 pts. 87 pts were registered in one of two efficacy cohorts: Cohort 1 included pts w no prior T for MBC. Pts with prior adjuvant T were included if the interval from last T to 1st recurrence > 12 months. Cohort 2 included pts with 1-2 prior lines of T for MBC or recurrence within 12 months of adjuvant T. An additional 29 pts were enrolled in a biomarker cohort (Cohort 3). Per-protocol efficacy analyses for 85 pts deemed evaluable are shown below: As we previously reported (Wagle et al, ASCO 2014), across 57 metastatic tumors, significant recurrently mutated genes were TP53 (n=30; 53%) and PIK3CA (n=19; 33%). The frequency of mutant TP53 and PIK3CA was not significantly different from 119 primary, treatment-naive HER2+ tumors sequenced in the TCGA study (50%, p=0.8 and 27%, p=0.5, respectively). Recurrent copy number alterations were also similar to TCGA data. Comparing the 38 pts who received any prior T with the 19 pts who did not, there was no significant difference in the incidence of mutant TP53 (53% vs 53%, p=1.0) and PIK3CA (37% vs 26%, p=0.6). We identified mutations in the HER2 kinase domain in 4/38 pts who received prior T (11%), as compared to 0/19 T-naive pts. HER2 kinase domain mutations have been identified in ∼2% of HER2-negative cancers but An analysis comparing paired archival primary tumors and baseline metastatic biopsies from 36 pts to identify genomic alterations acquired or enriched in the metastatic tumors will be presented. Conclusions: We present an analysis of the genomic landscape of HER2+ MBC, including comparisons between matched primary tumors and metastatic biopsies. Somatic HER2 kinase mutations in pts with HER2+ MBC treated with prior T suggests that these mutations may be involved in resistance to T, and may predict poor response to additional anti-HER2 therapy with combined L and T. Novel therapeutic approaches may be required for these pts. Citation Format: Nikhil Wagle, Nancy U Lin, Andrea L Richardson, Ignaty Leshchiner, Ingrid A Mayer, Andres Forero-Torres, Timothy J Hobday, Elizabeth C Dees, Rita Nanda, Mothaffar F Rimawi, Hao Guo, William T Barry, Ron Bose, Wei Shen, Antonio C Wolff, Stacey B Gabriel, Levi A Garraway, Eric P Winer, Ian E Krop. Whole exome sequencing (WES) of HER2+ metastatic breast cancer (MBC) from patients with or without prior trastuzumab (T): A correlative analysis of TBCRC003 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD3-5.

Validating CYP2D6 Genotype-Guided Tamoxifen Therapy for a Multiracial U.S. Population.

Background: Tamoxifen is a selective estrogen receptor modulator that is the most commonly used and cost effective agent for hormone sensitive breast cancer with documented efficacy in prevention, treatment of preneoplasia, and treatment in both the adjuvant and metastatic settings. However, tamoxifen is a prodrug, and up to half of those taking it may not receive the full benefit because of genetic differences in CYP2D6 that affect metabolism to its active form, endoxifen. Tamoxifen is FDA approved for use at both 20mg/day and 40 mg/day, however by convention is dosed at 20mg. We aimed to determine if endoxifen levels can be manipulated by genotype-guided dosing of tamoxifen.Methods: 118 patients on tamoxifen ≥ 4 months and not on potent CYP2D6 inhibiting medications enrolled in Lineberger Comprehensive Cancer Center (LCCC) trial 0801. Genotyping was performed using the CYP450 Amplichip® (Roche Diagnostics) for 2D6 alleles: *1-11, *15, *17, *19, *20, *29, *35, *36, *40, *41, *1XN, *2XN, *4XN, *10XN, *17XN, *35XN and *41 XN. Tamoxifen dose was increased from 20mg to 40mg in patients with any intermediate or poor metabolizing (IM or PM) alleles [but not in patients homozygous for extensive metabolizing (EM) alleles]. Endoxifen levels were drawn at baseline and 4 months later. Assuming that endoxifen levels in IM pts are 40% lower than EM at baseline (Jin et al., 2005) and with a one-sided significance level of 0.025 and a sample size of 40 patients with intermediate metabolizing CYP2D6 genotypes, this study would have 84% power to detect a 40% increase in endoxifen.Results: Of the 118 patients, 25 withdrew or were removed from study, leaving 93 who have completed this study and who are evaluable for the primary analysis. Genotyping results were presented at 2009 ASCO meeting (Irvin et al.). For this analysis, 19 (20%) are African-American, 69 (74%) are non-Hispanic white, 2 are Hispanic, and 3 are Asian. For the 93 evauable patients, genotyping revealed 31 (33%) EM/EM, 1 EM/UM (ultra-rapid), 20 (22%) EM/IM, 19 (20%) EM/PM, 4 (4%) IM/IM, 9 (10%) IM/PM, 9 (10%) PM/PM and 1 unknown. The primary outcome, the tamoxifen metabolite levels, including endoxifen, will be available in July.(Supported by NC University Cancer Research Fund, NCI SPORE, Laboratory Corporation of America, Roche Diagnostics) Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 410.

Patients' Understanding of a CYP2D6 Tamoxifen Genotyping Study.

Background: Pharmacogenomics is an emerging area for breast cancer research. Little is known about how well patients understand pharmacogenomics or the rationale for research in this area. The objective of this study was to analyze patient understanding of a clinical trial involving CYP2D6 genotyping to guide tamoxifen (T) therapy for breast cancer.Methods: We conducted a survey of understanding of pharmacogenomics and the purposes of a clinical trial among patients (pts) eligible for LCCC0801, a prospective Phase 2 study of CYP2D6 genotype-guided therapy for pts on tamoxifen for breast cancer. In this trial, we evaluated baseline endoxifen (E) levels and the impact of increased T dose to 40 mg/day among pts with any dysfunctional CYP2D6 alleles. The primary endpoint of change in E levels is not yet reported. All trial participants and those who declined participation were eligible for this survey. The research nurse administered 11 written questions at time of consent related to the purpose of this study and the nature of pharmacogenomic research. Pts had unlimited time to complete the survey written in a 5 point scale (strongly agree, agree, not sure, disagree, strongly disagree). For pts declining to enroll in the parent study, we offered an identical companion survey to which they could separately give consent.Results: Of 118 pts in the parent study, 117 completed the survey. Following informed consent, all respondents expressed confidence that they understood the purpose of the trial, 75% strongly agreed that they understood the purpose of the study. 98% of participants understood that this was a study of how different people respond to T, but 42% also incorrectly felt that this was a study of how different types of breast cancer respond to T, and 30% incorrectly felt that this study evaluated genetic risk for developing breast cancer. Though the consent form clearly stated that there may be no direct benefit to participants and that the purpose of the study was to help future pts, 68% reported that they would benefit directly, and only 22% felt the study was designed only to help future pts. When asked if the study involved genetics, 14% of pts disagreed, or were unsure. 45% of participants were uncomfortable or unsure with “having your doctor determine your T dose from the results of a genetic test.” Among a small sample of pts who declined trial participation but consented to the survey (13/30 decliners, 43%), compared to trial participants, fewer reported strong confidence in understanding the purpose of the trial (38% vs. 75%, p=0.0034), and a greater percentage identified an inaccurate purpose of the trial (69% vs. 42%, p = 0.043).Conclusions: After informed consent, a high percentage of participants in a pharmacogenomic clinical trial are able to correctly identify the primary purpose of the research, but a substantial minority hold false views about what the trial is designed to investigate. The majority of participants believe that they will directly benefit from trial participation, and few may understand that the primary purpose of the study is to improve care for future patients. Opportunities exist for improved understanding and communication of pharmacogenomic research and further evaluation of this area is needed. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6082.