Clinical Cancer Advances 2012 ASCO’s eighth annual Clinical Cancer Advances report identifies this year’s most significant clinical cancer advances Highlights 17 most important advances, along with 70 other notable advances in prevention and screening, treatment, and survivorship Overseen by 21-member editorial board of oncologists Complete 2012 CCA report is available: Interactive PDF at http://www.cancerprogress.net/cca Published in the Journal of Clinical Oncology, www.jco.org

Top Advances of 2012 Two new therapies delay progression of advanced breast cancer Pre-operative chemotherapy and radiation improves survival for patients with esophageal cancer Screening with flexible sigmoidoscopy reduces colorectal cancer incidence and death rates FDA approved a new targeted treatment for patients with advanced prostate cancer

Top 17 Advances Lenalinomide Maintenance Therapy Delays Multiple Myeloma Relapse after Stem-Cell Transplantation Two placebo-controlled phase III trials showed that lenalidomide (REVLIMID®)may be able to delay multiple myeloma relapses On average, patients relapsed after 41-46 months with lenalidomide therapy versus 23-27 months with placebo

Top 17 Advances New Armed Antibody Improves Survival in HER2 positive Metastatic Breast Cancer A randomized phase III trial found that an experimental drug called T-DM1 outperforms the current standard therapy for metastatic, HER2-positive breast cancer that is resistant to trastuzumab, increasing survival rates at 2 years from 47% to 65% T-DM1 is a “smart bomb” consisting of trastuzumab antibody linked to the chemotherapy drug DM1 In November 2012, FDA granted priority review for T-DM1

Top 17 Advances 3. Trial Finds Two HER2-Targeted Drugs Are Better than One in First-Line Therapy A phase III study showed that combining trastuzumab (Herceptin®) and docetaxel (Taxotere®) with pertuzumab (PERJETATM) may overcome or delay resistance to trastuzumab therapy in patients with HER2-positive breast cancer FDA approved pertuzumab in combination with pertuzumab and docetaxel in June 2012 as first-line treatment for patients with metastatic HER2-positive breast cancer

Top 17 Advances 4. Adding Targeted Therapy to Aromatase Inhibitor Delays Disease Progression in Postmenopausal Hormone Receptor-Positive Advanced Breast Cancer Phase III study found aromatase inhibitor exemestane (Aromasin®) plus everolimus (Afinitor®) delayed disease progression by six months compared with exemestane plus placebo FDA approved everolimus in July 2012 to treat certain women with advanced breast cancer

Top 17 Advances Preoperative Chemotherapy and Radiation Therapy Double Overall Survival for Esophageal and Gastroesophageal Junction Cancers Phase III trial showed that preoperative treatment with carboplatin (Paraplatin) and paclitaxel (Taxol) therapy and radiation therapy followed by surgery extended median overall survival from 24 to 49 months compared with surgery alone These findings will likely change the standard of care for most patients with esophageal and gastroesophageal junction cancers

Top 17 Advances Regorafenib Prolongs Overall Survival in Patients with Metastatic Colorectal Cancer Phase III trial showed that multitargeted drug regorafenib (Stivarga®) may extend overall survival in patients with metastatic colorectal cancer whose disease progressed after all standard therapies FDA approved regorafenib in Septemeber 2012 for this population of patients

Top 17 Advances 7. Enzalutamide Improves Survival and Becomes New Standard Treatment Option for Men with Chemotherapy-Treated Prostate Cancer Phase III trial of the androgen inhibitor enzalutamide (Xtandi®) in men with prostate cancer previously treated with docetaxel chemotherapy Median overall survival with enzalutamide was 18.4 months compared with 13.6 months with placebo The FDA approved enzalutamide in August 2012 for certain men with metastatic prostate cancer

Top 17 Advances 8. Chemotherapy Plus Bevacizumab Is More Effective than Chemotherapy Alone in Platinum-Resistant Recurrent Ovarian Cancer A Phase III trials found that adding bevacizumab (Avastin®) to standard chemotherapy delays disease progression for women with platinum-resistant ovarian cancer This is one of the first studies showing improved outcomes with targeted therapy and chemotherapy combinations in this patient population

Top 17 Advances 9. Cabozantinib Significantly Delays Medullary Thyroid Carcinoma Progression A randomized Phase III trial of the new multitargeted drug cabozantinib showed tumor shrinkage in 28 percent of patients treated with the drug Cabozantinib delayed disease progression by 7 months compared with placebo FDA approval of cabozantinib for patetients with advanced, inoperable medullary thyroid carcinoma is pending

Top 17 Advances Combination Chemotherapy Extends Survival in Certain Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC) Phase III trial showed that combination of pemetrexed (ALIMTA®) and carboplatin (Paraplatin) therapy may extend survival for patients with NSCLC who have performance score of 2 The median overall survival was 5.1 months for patients treated with pemetrexed and 9.6 months for those treated with combination therapy

Top 17 Advances Blocking the Hedgehog Pathway Stops Growth of Basal-Cell Carcinomas Phase II trial showed hedgehog inhibitor vismodegib (ErivedgeTM) is effective in both preventing and treating basal-cell carcinomas in patients with a rare, treatment-resistant, condition known as basal-cell nevus syndrome FDA approved vismodegib in January 2012 for patients with locally advanced basal-cell carcinoma who are not candidates for surgery or radiation therapy and for patients whose cancer has metastasized

Top 17 Advances Pazopanib Delays Cancer Progression in Patients with Chemotherapy-Resistant Metastatic Soft Tissue Sarcoma Phase III study in patients with advanced soft tissue sarcoma that progressed despite standard chemotherapy showed that targeted drug pazopanib (Votrient) may be beneficial On average, the disease progressed after 4.6 months for patients treated with pazopanib vs. 1.6 months for those treated with placebo; median overall survival was similar in the two groups

Top 17 Advances Screening with Flexible Sigmoidoscopy Reduces Deaths Resulting from Certain Colorectal Cancers A study involving more than 150,000 participants found that screening with flexible sigmoidoscopy reduces both colorectal cancer incidence and mortality As compared to usual care, screening with flexible sigmoidoscopy led to a 21% reduction in colorectal cancer incidence 26% reduction in deaths from the disease

Top 17 Advances 14. Study Shows Antipsychotic Drug Olanzapine May Control Breakthrough Chemotherapy-Induced Nausea and Vomiting Phase III trial showed that olanzapine (Zyprexa) is significantly more effective than the standard anti-nausea drug metoclopramide (Reglan) in controlling breakthrough chemotherapy-induced nausea and vomiting The findings address an unmet need for patients who experience such adverse effects despite routine preventive treatment

Top 17 Advances 15. Antidepressant Drug Duloxetine Relieves Pain from Chemotherapy-Induced Peripheral Neuropathy Phase III trial showed that duloxetine (Cymbalta®) is more effective than placebo for the treatment of painful peripheral neuropathy related to taxane- or platinum-based chemotherapy. Findings suggest that duloxetine may be a useful new treatment options for patients with cancer who suffer from this adverse effect

Top 17 Advances 16. Study Identifies Factors Affecting Whether Elderly Patients Can Safely Undergo Chemotherapy A study identified measures that are critical for helping physicians select appropriate treatments for elderly patients with cancer The findings suggest that pre-treatment mobility and nutritional assessment scores are particularly important in determining whether patients older than 70 years will benefit from chemotherapy

Top 17 Advances 17. Prospective Trial Reveals Factors that Predict Risk for Chemotherapy Side Effects in Older Adults Prospective study proposes a scoring system and risk stratification model that identifies adults at low, intermediate, and high risk of chemotherapy side effects The study provides a sorely needed tool to inform chemotherapy decision making for elderly patients with any type or stage of cancer

2012 Cancer Policy Developments Funding for Clinical Cancer Research ASCO’s initiative to build a rapid learning system for oncology ASCO’s recommendations to tackle drug shortages Recommendations for improving quality and value in cancer care

ASCO Resources ASCO Guidelines Cancer.Net Conquer Cancer Foundation www.asco.org/guidelines Cancer.Net www.cancer.net Conquer Cancer Foundation www.conquercancerfoundation.org ASCO Connection http://connection.asco.org

ASCO Resources Cancer Progress www.cancerprogress.net The cancerprogress.net site provides a dynamic and interactive history of progress against cancer, with stories of cancer survivors, advocates and physicians, and expert perspective on challenges we face to continue making progress.

susie.tappouni@asco.org 571-483-1355 ASCO’s Annual Report on Progress Against Cancer www.cancerprogress.net/cca For additional information, contact Susie Tappouni in ASCO’s Communications Department: susie.tappouni@asco.org 571-483-1355