DISSECTING THE DECISION Optimizing the Use of CDK4/6 Inhibitors in the Management of

1. DISSECTING THE DECISION Optimizing the Use of CDK4/6 Inhibitors in the Management of ER-Positive, HER2-Negative Metastatic Breast Cancer Co-Chairs Neil Love, MDSara M Tolaney, MD, MPH Faculty NeelimaDenduluri, MD ShomGoel, BMedSci, MBBS, PhD Erika Hamilton, MD KomalJhaveri, MD Ruth M O’Regan, MD

2. Overview of Clinical Practice for ER-Positive Metastatic Breast Cancer

3. Approximately how many patients with the following are currently under your care? (Median*) N = 100 US-based general medical oncologists • *Among oncologists seeing patients with this disease type

4. Median number of patients with breast cancer (N = 100) in your practice • Median number of new patients annually: 50 • Median number of deaths annually: 10 N = 100 US-based general medical oncologists

5. What would you estimate to be the approximate likelihood that a woman in your practice who presents with de novo ER-positive, HER2-negative mBC will be alive…  N = 100 US-based general medical oncologists

6. What would you estimate to be the approximate likelihood that a woman with ER-positive breast cancer in your practice who develops metastases 2 years after starting adjuvant endocrine therapy will be alive… N = 100 US-based general medical oncologists

7. If you have used the agent, approximately how many times have you administered the following to a patient with breast cancer outside of a clinical trial? N = 100 US-based general medical oncologists

8. When was the last time you initiated treatment with a CDK4/6 inhibitor in combination with endocrine therapy in a woman with ER-positive, HER2-negative metastatic breast cancer (mBC)? Within the past week Within the past month More than 1 month ago N = 100 US-based general medical oncologists

9. Within the past month Within the past month Within the past week Within the past week Within the past week Within the past week

10. What was the patient’s age? 30-40 41-50 51-60 61-70 71-80 N = 100 US-based general medical oncologists

11. 51-60 61-70 30-40 61-70 51-60 51-60

12. What was the patient’s menopausal status? Postmenopausal Perimenopausal Premenopausal N = 100 US-based general medical oncologists

13. Postmenopausal Postmenopausal Premenopausal Postmenopausal Postmenopausal Premenopausal

14. Which CDK4/6 inhibitor did the patient receive? Palbociclib Abemaciclib Ribociclib N = 100 US-based general medical oncologists

15. Abemaciclib Palbociclib Palbociclib Palbociclib Abemaciclib Ribociclib

16. Which therapy did the patient receive? Palbociclib/letrozole Palbociclib/anastrozole Palbociclib/fulvestrant Abemaciclib/fulvestrant Palbociclib/tamoxifen Ribociclib/exemestane Abemaciclib/anastrozole Ribociclib/letrozole Abemaciclib/letrozole Palbociclib/exemestane Ribociclib/anastrozole Ribociclib/tamoxifen Ribociclib/fulvestrant N = 100 US-based general medical oncologists

17. Abemaciclib/fulvestrant Palbociclib/letrozole Palbociclib/letrozole Palbociclib/fulvestrant Abemaciclib/letrozole Ribociclib/letrozole

18. What prior endocrine therapy, if any, had this patient received... As adjuvant treatment For metastatic disease None None Anastrozole Anastrozole Tamoxifen Tamoxifen Letrozole Letrozole Exemestane Exemestane Fulvestrant Fulvestrant N = 100 US-based general medical oncologists

19. As adjuvant treatment Anastrozole None Tamoxifen None None None

20. For metastatic disease None None None Letrozole None None

21. What sites of metastases did this patient have? (Select all that apply.) Bone Lung Liver Brain Other N = 100 US-based general medical oncologists

22. Bone Bone, liver Liver Bone Bone, liver Bone, mediastinal nodes

23. Did this patient benefit from this treatment? Yes, and she experienced an objective response Yes, but she did not experience an objective response Still too early to make a determination No N = 100 US-based general medical oncologists

24. Still too early to make a determination Yes, and she experienced an objective response Still too early to make a determination Still too early to make a determination Still too early to make a determination Still too early to make a determination

25. Did the patient experience any treatment complications that required active management? No Yes, but the dose of treatment did not require adjustment Yes, and the dose of treatment required adjustment N = 100 US-based general medical oncologists

26. Yes, but the dose of treatment did not require adjustment Yes, and the dose of treatment required adjustment No No No No

27. Selection of First-Line Endocrine Therapy for Postmenopausal Women with ER-Positive, HER2-Negative Metastatic Breast Cancer

28. A 65-year-old woman presents with de novo ER-positive, HER2-negative mBC with asymptomatic bone metastases. Which endocrine-based treatment would you most likely recommend? ç N = 100 US-based general medical oncologists

29. Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole

30. A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 2 years after starting adjuvant anastrozole. Which endocrine-based treatment would you most likely recommend? ç N = 100 US-based general medical oncologists

31. Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Abemaciclib + fulvestrant Ribociclib + fulvestrant

32. A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 4.5 years after starting adjuvant anastrozole. Which endocrine-based treatment would you most likely recommend? ç N = 100 US-based general medical oncologists

33. Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Ribociclib + fulvestrant

34. A 65-year-old woman has completed 5 years of adjuvant anastrozole for an ER-positive, HER2-negative IDC but has now developed asymptomatic bone metastases 2 years after completing adjuvant hormonal therapy. Which endocrine-based treatment would you most likely recommend? ç N = 100 US-based general medical oncologists

35. Palbociclib + fulvestrant Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole

36. A 65-year-old woman has completed 5 years of adjuvant anastrozole for an ER-positive, HER2-negative IDC but has now developed asymptomatic bone metastases 5 years after completing adjuvant hormonal therapy. Which endocrine-based treatment would you most likely recommend? ç N = 100 US-based general medical oncologists

37. Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole

38. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 70-year-old woman presenting with de novo ER-positive, HER2-negative mBC with asymptomatic bone metastases? N = 100 US-based general medical oncologists

39. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

40. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 70-year-old woman with ER-positive, HER2-negative, node-negative breast cancer who has developed asymptomatic bone metastases 2 years after starting adjuvant anastrozole? N = 100 US-based general medical oncologists

41. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, ribociclib

42. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 70-year-old woman who has completed 5 years of adjuvant anastrozole for an ER-positive, HER2-negative IDC but has now developed asymptomatic bone metastases 2 years after completing adjuvant hormonal therapy? N = 100 US-based general medical oncologists

43. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

44. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 75-year-old woman presenting with de novo ER-positive, HER2-negative mBC with asymptomatic bone metastases? N = 100 US-based general medical oncologists

45. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, ribociclib

46. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 75-year-old woman with ER-positive, HER2-negative, node-negative breast cancer who has developed asymptomatic bone metastases 2 years after starting adjuvant anastrozole? N = 100 US-based general medical oncologists

47. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

48. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for a 75-year-old woman who has completed 5 years of adjuvant anastrozole for an ER-positive, HER2-negative IDC but has now developed asymptomatic bone metastases 2 years after completing adjuvant hormonal therapy? N = 100 US-based general medical oncologists

49. Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

50. Do you generally add a CDK4/6 inhibitor to endocrine therapy (in addition to any other systemic or local therapy) for an 80-year-old woman presenting with de novo ER-positive, HER2-negative mBC with asymptomatic bone metastases? N = 100 US-based general medical oncologists