1. Patterns of Care in Medical Oncology Systemic Therapy for Metastatic Disease

2. When you use ovarian suppression for a premenopausal patient with metastatic breast cancer, which regimen do you generally recommend? 24% 76% 40% 60% Leuprolide or goserelin every three months Monthly leuprolide or monthly goserelin Clinical investigators Practicing oncologists

3. Which first-line endocrine therapy would you generally use on progression after 4 years of adjuvant anastrozole? 5% 2% Other 12% 0% Letrozole 19% 14% Exemestane 39% 45% 45% 19% Fulvestrant Tamoxifen Clinical investigators Practicing oncologists

4. What percent of your patients with metastatic breast cancer would prefer to receive a monthly injection of fulvestrant rather than a daily oral endocrine agent such as an aromatase inhibitor or tamoxifen? 20% 28% Mean Clinical investigators Practicing oncologists

5. One acceptable clinical option for patients with ER-positive tumors who develop progressive metastatic disease on an AI is to continue the AI and add fulvestrant. 46% 74% Disagree 16% 10% 33% 21% In between Agree Clinical investigators Practicing oncologists

6. When using fulvestrant in the metastatic setting, do you generally use a loading dose? 2007 2006 2005 47% 37% 16% Percent answering yes Practicing oncologists (PO) Clinical investigators (CI) 76% 53% 67% Percent answering yes

7. A 60-year-old woman was diagnosed 3 years earlier with ER-positive, PR-positive, HER2-positive breast cancer and received adjuvant AC followed by tamoxifen , which she has now received for 3 years. She did not receive adjuvant trastuzumab. She now presents with moderately symptomatic bone metastases and no other sites of disease on staging. Which therapy would you recommend to this patient? 17% 24% Endocrine therapy alone 3% 0% Endocrine therapy + chemotherapy 11% 0% Endocrine therapy + chemotherapy + trastuzumab 10% 66% 11% 58% Chemotherapy + trastuzumab Endocrine therapy + trastuzumab Clinical investigators Practicing oncologists

8. If endocrine therapy alone or in combination was chosen above, which endocrine therapy would you recommend? 8% 7% Fulvestrant 14% 11% Exemestane 18% 64% 8% 70% Letrozole Anastrozole Clinical investigators Practicing oncologists

9. A 60-year-old asymptomatic woman presents with de novo metastatic disease to bone and liver. A breast biopsy shows an ER-positive, PR-positive, HER2-positive tumor, and a liver biopsy confirms metastatic disease. Which is your most likely initial treatment strategy? 20% 4% Endocrine therapy + chemotherapy + trastuzumab 12% 28% Endocrine therapy alone 31% 37% 31% 37% Endocrine therapy + trastuzumab Chemotherapy + trastuzumab Clinical investigators Practicing oncologists

10. Have you used nanoparticle or nab paclitaxel? If yes, in how many patients? 2007 2005 74% 62% Percent answering yes Practicing oncologists (PO) Clinical investigators (CI) 98% 73% Percent answering yes 2007 2005 12 2 Mean Practicing oncologists (PO) Clinical investigators (CI) 17 4 Mean

11. In your opinion, how would you compare the resolution of Grade III/IV neuropathy experienced by patients receiving nab paclitaxel versus paclitaxel? 3% 2% Patients tend to experience resolution of neuropathy faster on paclitaxel 61% 37% 42% 55% No difference Patients tend to experience resolution of neuropathy faster on nab paclitaxel Clinical investigators Practicing oncologists

12. Approximately what percent of your patients have experienced an allergic reaction when using the following taxanes for breast cancer? 9% 4% Mean Paclitaxel 6% 11% Docetaxel Mean Clinical investigators Practicing oncologists

13. Approximately how many of the patients in your practice in the last 3 years, if any, have had a significant infusion reaction when using the following taxanes? 6 3 Mean Paclitaxel 7 9 Docetaxel Mean Clinical investigators Practicing oncologists

14. A 53-year-old woman with metastatic breast cancer, bone-only metastases and minimal symptoms will receive one of the following therapies. Please indicate the premedications you would use for each one of these regimens: * Primarily antiemetics 52% 6% 4% 93% 6% 1% None 17% 18% 30% 6% 10% 31% Other* 30% 93% 94% 1% 94% 98% Dexamethasone Antihistamines 22% 2% Nab paclitaxel 34% 93% 53% 91% Docetaxel Paclitaxel Clinical investigators Practicing oncologists

15. What percent of your patients with breast cancer do you think would prefer not having to receive premedication for taxanes? What percent of your patients with breast cancer do you think would consider it an important advantage to have a shorter infusion time? 76% 48% Mean Clinical investigators Practicing oncologists 70% 61% Mean

16. Approximately what percent of patients with metastatic breast cancer who receive taxane premedication with dexamethasone develop the following symptoms? (Mean) 18% 9% Exacerbation or new onset of diabetes 17% 16% Agitation to the point that it is bothersome 22% 38% 19% 36% Weight gain to the point that it is bothersome At least one night of insomnia Clinical investigators Practicing oncologists

17. If cost and reimbursement for nab paclitaxel were the same as for paclitaxel, with what percent of patients to whom you would currently recommend paclitaxel for metastatic breast cancer would you use nab paclitaxel instead? 80% 64% Mean Clinical investigators Practicing oncologists

18. A 60-year-old woman presents with de novo metastatic ER-negative, PR-negative, HER2-negative breast cancer. She has bone and lung metastases and is mildly symptomatic. Her health insurance will cover 100% of any therapy you prescribe. You have decided to use a taxane as part of your treatment strategy. Which taxane, if any, would you most likely recommend for this patient? 38% 6% Docetaxel 39% 55% 23% 39% Paclitaxel Nab paclitaxel Clinical investigators Practicing oncologists

19. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received adjuvant AC. She now presents with moderately symptomatic bone metastases and no other sites of disease on staging. How would you compare the following agents/regimens for this particular case? Your preferred docetaxel-based regimen (Doc) versus your preferred nab paclitaxel-based regimen ( Nab ): Efficacy 2007 2006 8% 0% Nab is significantly more efficacious Clinical investigators (CI) 45% 43% 4% 0% 7% Nab is somewhat more efficacious 91% 2% 0% Both are similar in efficacy Doc is somewhat more efficacious Doc is significantly more efficacious

20. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received adjuvant AC. She now presents with moderately symptomatic bone metastases and no other sites of disease on staging. How would you compare the following agents/regimens for this particular case? Your preferred docetaxel-based regimen (Doc) versus your preferred nab paclitaxel-based regimen ( Nab ): Efficacy 2007 2006 2% 0% Nab is significantly more efficacious Practicing oncologists (PO) 27% 57% 12% 2% 18% Nab is somewhat more efficacious 69% 12% 1% Both are similar in efficacy Doc is somewhat more efficacious Doc is significantly more efficacious

21. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received adjuvant AC. She now presents with moderately symptomatic bone metastases and no other sites of disease on staging. How would you compare the following agents/regimens for this particular case? Your preferred docetaxel-based regimen (Doc) versus your preferred nab paclitaxel-based regimen ( Nab ): Safety and tolerability 2007 2006 Clinical investigators (CI) 16% 7% Nab has significantly better safety and tolerability 62% 18% 0% 4% 59% Nab has somewhat better safety and tolerability 32% 2% 0% Both are similar in safety and tolerability Doc has somewhat better safety and tolerability Doc has significantly better safety and tolerability

22. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received adjuvant AC. She now presents with moderately symptomatic bone metastases and no other sites of disease on staging. How would you compare the following agents/regimens for this particular case? Your preferred docetaxel-based regimen (Doc) versus your preferred nab paclitaxel-based regimen ( Nab ): Safety and tolerability 2007 2006 Practicing oncologists (PO) 7% 7% Nab has significantly better safety and tolerability 46% 35% 9% 3% 44% Nab has somewhat better safety and tolerability 39% 7% 3% Both are similar in safety and tolerability Doc has somewhat better safety and tolerability Doc has significantly better safety and tolerability

23. Have you used bevacizumab for metastatic breast cancer off protocol? 2007 2006 2005 64% 49% 4% Percent answering yes Practicing oncologists (PO) Clinical investigators (CI) 96% 73% 89% Percent answering yes

24. Have you used endocrine therapy in combination with bevacizumab? 24% 27% Percent answering yes Clinical investigators Practicing oncologists

25. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Capecitabine + bevacizumab 2007 2006 Clinical investigators (CI) 24% 24% 52% 34% 24% 42% Disagree In between Agree

26. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Capecitabine + bevacizumab 2007 2006 Practicing oncologists (PO) 19% 32% 49% 27% 32% 41% Disagree In between Agree

27. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Capecitabine + paclitaxel + bevacizumab 2007 2006 Clinical investigators (CI) 53% 25% 22% 44% 27% 29% Disagree In between Agree

28. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Capecitabine + paclitaxel + bevacizumab 2007 2006 Practicing oncologists (PO) 24% 39% 37% 21% 41% 38% Disagree In between Agree

29. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Carboplatin + paclitaxel + bevacizumab 2007 2006 Clinical investigators (CI) 33% 28% 39% 34% 32% 34% Disagree In between Agree

30. For patients with ER-negative, PR-negative, HER2-negative tumors, the following bevacizumab therapy combinations are potentially acceptable in the first-line setting. Carboplatin + paclitaxel + bevacizumab 2007 2006 Practicing oncologists (PO) 19% 32% 49% 17% 35% 48% Disagree In between Agree

31. For a patient who presents with asymptomatic metastatic disease and no prior systemic therapy, how would you compare capecitabine to capecitabine + bevacizumab? 6% 6% Capecitabine + bevacizumab is significantly more efficacious 62% 66% Capecitabine + bevacizumab is somewhat more efficacious 28% 24% Both are similar in efficacy 2% 4% Capecitabine is somewhat more efficacious Efficacy 0% 2% Capecitabine is significantly more efficacious Clinical investigators Practicing oncologists

32. For a patient who presents with asymptomatic metastatic disease and no prior systemic therapy, how would you compare capecitabine to capecitabine + bevacizumab? 1% 0% Capecitabine + bevacizumab has significantly better safety and tolerability 4% 4% Capecitabine + bevacizumab has somewhat better safety and tolerability 44% 14% Both are similar in safety and tolerability 41% 74% Capecitabine has somewhat better safety and tolerability Safety and tolerability 8% 10% Capecitabine has significantly better safety and tolerability Clinical investigators Practicing oncologists

33. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received AC. She now has moderately symptomatic bone metastases and no other sites of disease on staging. Which therapy would you recommend to this patient? 46% 55% Chemotherapy + bevacizumab Assuming cost and reimbursement were an issue 45% 54% Chemotherapy alone Clinical investigators Practicing oncologists

34. A 60-year-old woman was diagnosed 3 years earlier with ER-negative, PR-negative, HER2-negative breast cancer and received AC. She now has moderately symptomatic bone metastases and no other sites of disease on staging. Which therapy would you recommend to this patient? 62% 80% Chemotherapy + bevacizumab Assuming cost and reimbursement were not an issue 20% 38% Chemotherapy alone Clinical investigators Practicing oncologists

35. A 60-year-old woman received AC for an ER-negative, PR-negative, HER2-negative tumor. One year later, she is diagnosed with asymptomatic bone metastases and two small pulmonary nodules. Cost and reimbursement issues aside, which therapy is likely to provide the best therapeutic ratio? 15% 2% A taxane 13% 6% Capecitabine + bevacizumab 11% 18% Capecitabine 74% 61% A taxane + bevacizumab Clinical investigators Practicing oncologists

36. If the patient receives capecitabine and shows a response but the disease progresses after 9 months of therapy, which therapy would then provide the best therapeutic ratio? 6% 4% Other 25% 22% A taxane 74% 69% A taxane + bevacizumab Clinical investigators Practicing oncologists

37. A 60-year-old woman received AC for an ER-negative, PR-negative, HER2-negative tumor. Three years later , she is diagnosed with very symptomatic bone metastases and multiple hepatic and pulmonary nodules . Cost and reimbursement issues aside, which therapy is likely to provide the best therapeutic ratio? 10% 6% Other 7% 2% Capecitabine 11% 2% A taxane 15% 6% A taxane + capecitabine 84% 57% A taxane + bevacizumab Clinical investigators Practicing oncologists

38. Same patient: One year later , she is diagnosed with asymptomatic bone metastases and 2 small pulmonary nodules and receives docetaxel. She shows a response, but the disease progresses after a total of 9 months of therapy. Cost and reimbursement issues aside, which therapy is likely to provide the best therapeutic ratio? 13% 0% Other 15% 2% Paclitaxel + bevacizumab 13% 4% Nab paclitaxel + bevacizumab 29% 35% Viborelbine or capecitabine + bevacizumab 59% 30% Capecitabine Clinical investigators Practicing oncologists

39. Have you used the metronomic regimen of bevacizumab, cyclophosphamide and methotrexate presented by Harold Burstein at the 2005 San Antonio meeting? 2007 2006 4% 8% Percent answering yes Practicing oncologists (PO) Clinical investigators (CI) 31% 24% Percent answering yes

40. Patients with metastatic disease experiencing prolonged useful responses to bevacizumab with chemotherapy should be presented with the option of continuing bevacizumab and switching to another chemotherapy at the time of progression. 18% 49% Disagree 35% 22% In between 29% 47% Agree Clinical investigators Practicing oncologists

41. Are you familiar with the RIBBON trials 1 and 2? If yes, have you enrolled patients in these trials? 78% 21% Percent answering yes Clinical investigators Practicing oncologists 38% 32% Percent answering yes

42. Taking into consideration the safety, tolerability, cost and reimbursement of the following metastatic breast cancer treatments, how much of a benefit in progression-free survival would you require clinical trials to demonstrate for you to generally prefer that therapy ? Assume that the available trial data are not mature enough to evaluate overall survival. To generally prefer nab paclitaxel over standard paclitaxel 3.6 4.6 Mean number of months Clinical investigators Practicing oncologists

43. Taking into consideration the safety, tolerability, cost and reimbursement of the following metastatic breast cancer treatments, how much of a benefit in progression-free survival would you require clinical trials to demonstrate for you to generally prefer that therapy ? Assume that the available trial data are not mature enough to evaluate overall survival. To generally prefer bevacizumab + paclitaxel over paclitaxel alone 4.5 5.1 Mean number of months Clinical investigators Practicing oncologists

44. Taking into consideration the safety, tolerability, cost and reimbursement of the following metastatic breast cancer treatments, how much of a benefit in progression-free survival would you require clinical trials to demonstrate for you to generally prefer that therapy ? Assume that the available trial data are not mature enough to evaluate overall survival. To generally prefer trastuzumab + an aromatase inhibitor over an aromatase inhibitor alone 4.1 5.1 Mean number of months Clinical investigators Practicing oncologists