CP Overview of NCCTG Group Organization and Research Jan C. Buckner, MD Group Chair November 12, 2010

CP Idea Generators NCCTG Programs NCCTG Leadership NCCTG Organizational Overview MCCC and other academic centers Cooperative groups Industry NCI Community Oncologists Community Oncology Programs

CP Community-Based Partnership

NCCTG in 1977

CP WA OR ID MT Saskatchewan WY UT NV CA AZ NM CO NE SD ND MN MO KS FL NC MI KY OH WV VA PA NY MD DE NJ CT RI MA ME NH VT IA IL WI DC GA TXLA AR AL TN MS OK SC IN The 43 NCCTG Memberships Are Headquartered in 30 States & CanadaHI AK

CP NCCTG has 392 treating locations in 35 states as well as Canada AK 1 WA OR ID MT Saskatchewan WY UT NV CA AZ NM CO NE SD ND MN MO KS FL NC MI KY OH VA PA NY MD DE NJ CT RI MA ME NH VT IA IL WI DC GA 2 TXLA AR AL TN MS OK SC 3 IN WV HI 18

CP Community Member Involvement Co-Chairs of scientific committees Participate in protocol review Co-chairs of protocols ~80% of accrual Audits Patient Advocate Network

CP NCCTG Organizational Overview NCCTG Leadership Idea Generators Clinical data Biospecimens MCCC and other academic centers Cooperative groups Industry NCI Community Oncologists Community Oncology Programs

CP Mayo Clinic Cancer Center Leadership Integrated systems Financial support

CP Mayo Clinic Cancer Center Leadership Integrated systems Financial support

CP Mayo Clinic Cancer Center Leadership Integrated systems Financial support

CP Trial design and conduct To improve clinical trial design and conduct 1 Improved therapeutics To improve the duration and quality of life of cancer patients Specific Aims 22 Translational research To improve the understanding of cancer biology and the biological consequences of treatment 4 Cancer prevention and control To provide an infrastructure for studies of cancer prevention and symptom management

CP NCCTG Strategic Plan Goals 1. To advance the practice of oncology by performing high quality clinically relevant trials in the community 2. To enhance the science of cancer care by promoting translational research 3. To expand research portfolio to include screening, prevention, survivorship and biomarker trials

CP NCCTG Strategic Plan Goals 4. To enhance the delivery of cancer care 5. To enhance collaboration with cooperative groups and other research organizations with similar mission 6. To improve trial quality and conduct to achieve maximum value

CP NCCTG Committees Discipline-Oriented Scientific Cancer Control Novel Therapeutics Quality of Life Modality Pathology Radiation Oncology Surgery Core Function Audit Cancer Health Disparity Oncology Nursing Clinical Research Assoc Board Patient Advocates Statistics and Data Center Biostatistics Advisory Translational Research Coord BreastGastrointestinalLungNeuro-oncology Disease Specific LIAISONS

CP Aim 1 Improved Therapeutics To improve the duration and quality of life of cancer patients

NSABP B-31/N9831 Joint Analysis: Impact of Adding Trastuzumab to AC  Paclitaxel on Disease-Free Survival* Aim 1 Improved Therapeutics Accomplishment *N9831 arm B (sequential trastuzumab after ACP) not included in joint analysis Romond et al. N Engl J Med 2005;353: Trastuzumab (133 events) Control (261 events) % surviving disease-free Years after randomization P< HR=0.48 Median FU 2.0 yr 87.1% 85.3% 67.1% 75.4% CP

N9741: Establishing FOLFOX as standard 1st line therapy N=795 Irinotecan + oxaliplatin(IROX) 5-FU/LV(IFL) Oxaliplatin + 5-FU/LV (FOLFOX) R Goldberg RM et al: J Clin Oncol Years % alive Median IFL 14.8 mo FOLFOX19.5 mo IROX 17.4 mo P= P=0.09 P=0.04 CP Aim 1 Improved TherapeuticsAccomplishment

CP Nelson, NEJM, 2004; 350:2050 NCCTG (INT0146) Phase III Laparoscopic Colon Trial Cumulative Incidence of Recurrence Years P=0.32 Overall Survival (%) Years Colectomy Open Laparoscopically-assisted P=0.51 Aim 1 Improved TherapeuticsAccomplishment

CP : RT in LGG Aim 1 Improved TherapeuticsAccomplishment Shaw et al: JCO 2002; 20: Brown et al: JCO 2003; 21: Overall Survival (%) Years from randomization P= Gy 64.8 Gy

CP Aim 1 Improved TherapeuticsFuture Plans THE PATIENT Targeted therapies Chemo- therapy Radiation Surgery Measure of Success Survival AND Quality of Life

CP Aim 2 Translational Research To improve the understanding of cancer biology and the biological consequences of treatment

CP Goetz et al J Clin Oncol. 2005;23(36): CYP2D6 and Tamoxifen Relapse-free Survival % Years after randomization CYP2D6 WT/WT CYP2D6 *4/WT P=0.020 CYP2D6 *4/* Aim 2 Translational ResearchAccomplishment

CP t(1p;19q) and Survival in LGG Aim 2 Translational ResearchAccomplishment Jenkins et al (in press) Overall Survival (%) Years of follow-up P=0.003 Fusion No fusion Median survival (yr)

CP Aim 2 Translational ResearchFuture Plans THE PATIENT Patient Biology Pharmaco- genomics Immunology Tumor Biology Tumor tissue biomarkers

CP Aim 3 Trial Methodology To improve methods for performing clinical trials

CP year DFS vs 5-year OS Sargent et al, JCO 2005 Overall survival 5 yr OS= *3 yr DFS May 05, 2004: ODAC recommends 3-yr DFS as new regulatory endpoint for full approval in adjuvant colon cancer 20,898 patients, 18 trials Disease-free survival Aim 3 Trial Methodology Accomplishment

CP Aim 3 Trial Methodology Months Progression-free at 6 mo Progressor at 6 mo Median survival (mo.) Survival (%) Overall Survival Recurrent GBM Patients Accomplishment Ballman et al: Neuro-Oncol (in press)

CP Sloan, Cella, Hays: JCE 2005, December Norman, Sloan, Wyrwich: Medical Care 41(5): , 2003 Aim 3 Trial Methodology Accomplishment 10 Point (1/2 Standard Deviation) Decrease in Fatigue Placebo Epoetin Alfa BaselineCycle 1Cycle 2Cycle 3Cycle 4 %

CP Questions