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, MD Sara M Tolaney, MD, MPH Faculty Neelima Denduluri, MD Komal Jhaveri, MD Shom Goel, BMedSci, MBBS, PhD Ruth M O’Regan, MD Erika Hamilton, MD

Overview of Clinical Practice for ER-Positive Metastatic Breast Cancer

Approximately how many patients with the following are currently under your care? (Median*) Solid tumors Number of patients Breast cancer 100 Lung cancer 58 Colorectal cancer 50 Pancreatic cancer 15 Gastric cancer 10 Ovarian cancer Prostate cancer 25 Renal cell carcinoma 14 Bladder cancer Soft tissue sarcoma 5 Hematologic cancers Number of patients Chronic lymphocytic leukemia 25 Hodgkin lymphoma 10 Mantle cell lymphoma 6 Follicular lymphoma 20 Diffuse large B-cell lymphoma 15 Acute myeloid leukemia Acute lymphocytic leukemia 7 N = 100 US-based general medical oncologists *Among oncologists seeing patients with this disease type

Adjuvant/ neoadjuvant Median number of patients with breast cancer (N = 100) in your practice Adjuvant/ neoadjuvant Metastatic ER-positive, HER2-negative 25 20 HER2-positive 15 10 Triple-negative 12 Median number of new patients annually: 50 Median number of deaths annually: 10 N = 100 US-based general medical oncologists

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…  Median 2 years after initial presentation 80% 5 years after initial presentation 50% 10 years after initial presentation 22% N = 100 US-based general medical oncologists

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… Median 2 years after presenting with metastatic disease 70% 5 years after presenting with metastatic disease 45% 10 years after presenting with metastatic disease 20% N = 100 US-based general medical oncologists

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? Median Palbociclib 15 Ribociclib 6 Abemaciclib 5 Abemaciclib monotherapy 4 N = 100 US-based general medical oncologists

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

Within the past month Within the past month Within the past week Within the past week Within the past week Within the past week

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

51-60 61-70 30-40 61-70 51-60 51-60

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

Postmenopausal Postmenopausal Premenopausal Postmenopausal Postmenopausal Premenopausal

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

Abemaciclib Palbociclib Palbociclib Palbociclib Abemaciclib Ribociclib

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

Abemaciclib/fulvestrant Palbociclib/letrozole Palbociclib/letrozole Palbociclib/fulvestrant Abemaciclib/letrozole Ribociclib/letrozole

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

As adjuvant treatment Anastrozole None Tamoxifen None None None

For metastatic disease None None None Letrozole None None

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

Bone, mediastinal nodes Bone, liver Liver Bone Bone, liver Bone, mediastinal nodes

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

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

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

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

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

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 CDK4/6 inhibitor 68% Choice of endocrine therapy AI 71% Fulvestrant 22% Tamoxifen 7% N = 100 US-based general medical oncologists

Palbociclib + letrozole

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 CDK4/6 inhibitor 86% Choice of endocrine therapy AI 27% Fulvestrant 71% Tamoxifen 2% N = 100 US-based general medical oncologists

Palbociclib + fulvestrant Abemaciclib + fulvestrant Ribociclib + fulvestrant

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 CDK4/6 inhibitor 84% Choice of endocrine therapy AI 26% Fulvestrant 73% Tamoxifen 1% N = 100 US-based general medical oncologists

Palbociclib + fulvestrant Ribociclib + fulvestrant

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 CDK4/6 inhibitor 81% Choice of endocrine therapy AI 54% Fulvestrant 44% Tamoxifen 2% N = 100 US-based general medical oncologists

Palbociclib + fulvestrant Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole Palbociclib + letrozole

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 CDK4/6 inhibitor 76% Choice of endocrine therapy AI 58% Fulvestrant 39% Tamoxifen 3% N = 100 US-based general medical oncologists

Palbociclib + letrozole

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, ribociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, ribociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib Yes, palbociclib

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

Yes, palbociclib Yes, palbociclib Yes, palbociclib No No No

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 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

Yes, palbociclib Yes, palbociclib Yes, palbociclib No Yes, palbociclib Yes, palbociclib

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 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

Yes, palbociclib Yes, palbociclib Yes, palbociclib No No Yes, palbociclib

Based on current clinical trial data and your personal experience, how would you generally compare to endocrine therapy in patients presenting with de novo metastatic disease versus those who experience relapse while receiving adjuvant endocrine therapy? About the same Greater benefit in patients with de novo metastatic disease Greater benefit in patients who experience relapse while receiving adjuvant endocrine therapy I don't know N = 100 US-based general medical oncologists

About the same About the same About the same About the same Greater benefit in patients who experience relapse while receiving adjuvant endocrine therapy About the same

Based on current clinical trial data and your personal experience, how would you generally compare the efficacy of CDK4/6 inhibitors in combination with endocrine therapy in older (eg, older than age 70) versus younger patients with ER-positive, HER2-negative mBC? About the same They are more efficacious in younger patients They are more efficacious in older patients I don't know N = 100 US-based general medical oncologists

About the same About the same About the same About the same About the same About the same

Based on current clinical trial data and your personal experience, how would you generally compare the tolerability/toxicity of CDK4/6 inhibitors in combination with endocrine therapy in older (eg, older than age 70) versus younger patients with ER-positive, HER2-negative mBC? About the same They are less toxic in younger patients They are less toxic in older patients I don't know N = 100 US-based general medical oncologists

They are less toxic in younger patients About the same About the same They are less toxic in younger patients They are less toxic in younger patients They are less toxic in younger patients

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

A 40-year-old premenopausal woman presents at first diagnosis with ER-positive, HER2-negative mBC with asymptomatic bone metastases. Which endocrine-based treatment would you most likely recommend? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Tamoxifen + Ox Palbociclib + tamoxifen + Ox Ribociclib + letrozole + Ox Palbociclib + fulvestrant + Ox ç Abemaciclib + fulvestrant + Ox CDK4/6 inhibitor 61% Choice of endocrine therapy AI 48% Fulvestrant 14% Tamoxifen 38% Ribociclib + fulvestrant + Ox Abemaciclib + letrozole + Ox Tamoxifen Anastrozole + Ox Letrozole + Ox Exemestane + Ox N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 2 years after starting adjuvant tamoxifen. Which endocrine-based treatment would you most likely recommend? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + fulvestrant + Ox ç CDK4/6 inhibitor 60% Choice of endocrine therapy AI 79% Fulvestrant 21% Tamoxifen 0% Ribociclib + letrozole + Ox Ribociclib + fulvestrant + Ox Palbociclib + fulvestrant + Ox Abemaciclib + letrozole + Ox Letrozole + Ox Exemestane + Ox Anastrozole + Ox N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 4.5 years after starting adjuvant tamoxifen. Which endocrine-based treatment would you most likely recommend? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Ribociclib + letrozole + Ox Abemaciclib + fulvestrant + Ox ç CDK4/6 inhibitor 82% Choice of endocrine therapy AI 61% Fulvestrant 39% Tamoxifen 0% Ribociclib + fulvestrant + Ox Abemaciclib + letrozole + Ox Anastrozole + Ox Exemestane + Ox Letrozole + Ox N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 2 years after starting adjuvant tamoxifen and an LHRH agonist. Which endocrine-based treatment would you most likely recommend? Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + letrozole + Ox Ribociclib + letrozole + Ox Abemaciclib + letrozole + Ox ç CDK4/6 inhibitor 91% Choice of endocrine therapy AI 59% Fulvestrant 41% Tamoxifen 0% Abemaciclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox Exemestane + Ox Letrozole + Ox Anastrozole + Ox N = 100 US-based general medical oncologists

Palbociclib + letrozole + Ox Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + letrozole + Ox Palbociclib + letrozole + Ox Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 4.5 years after starting adjuvant tamoxifen and an LHRH agonist. Which endocrine-based treatment would you most likely recommend? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox Ribociclib + letrozole + Ox ç CDK4/6 inhibitor 88% Choice of endocrine therapy AI 57% Fulvestrant 43% Tamoxifen 0% Abemaciclib + fulvestrant + Ox Abemaciclib + letrozole + Ox Anastrozole + Ox Exemestane + Ox Letrozole + Ox N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases  2 years after starting adjuvant anastrozole and an LHRH agonist. Which endocrine-based treatment would you most likely recommend? Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Ribociclib + fulvestrant + Ox Palbociclib + letrozole + Ox Abemaciclib + fulvestrant + Ox Ribociclib + letrozole + Ox ç CDK4/6 inhibitor 92% Choice of endocrine therapy AI 25% Fulvestrant 61% Tamoxifen 13% Palbociclib + tamoxifen + Ox Abemaciclib + tamoxifen + Ox Abemaciclib + letrozole + Ox Tamoxifen + Ox Anastrozole + Ox Letrozole + Ox Other N = 100 US-based general medical oncologists

Abemaciclib + fulvestrant + Ox Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Abemaciclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox

A 40-year-old premenopausal woman with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 4.5 years after starting adjuvant anastrozole and an LHRH agonist. Which endocrine-based treatment would you most likely recommend? Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Ribociclib + fulvestrant + Ox Abemaciclib + fulvestrant + Ox Palbociclib + letrozole + Ox Ribociclib + letrozole + Ox Abemaciclib + tamoxifen + Ox ç CDK4/6 inhibitor 91% Choice of endocrine therapy AI 29% Fulvestrant 61% Tamoxifen 9% Abemaciclib + letrozole + Ox Palbociclib + tamoxifen + Ox Letrozole + Ox Tamoxifen + Ox Anastrozole + Ox Exemestane + Ox Other N = 100 US-based general medical oncologists

Abemaciclib + fulvestrant + Ox Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + ovarian suppression/ablation (Ox) Abemaciclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant tamoxifen 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? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Abemaciclib + fulvestrant + Ox Ribociclib + letrozole + Ox Palbociclib + tamoxifen + Ox Ribociclib + fulvestrant + Ox ç CDK4/6 inhibitor 87% Choice of endocrine therapy AI 56% Fulvestrant 33% Tamoxifen 10% Abemaciclib + letrozole + Ox Abemaciclib + tamoxifen + Ox Anastrozole + Ox Letrozole + Ox Tamoxifen + Ox Exemestane + Ox Other N = 100 US-based general medical oncologists

Abemaciclib + letrozole + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant tamoxifen 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? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Ribociclib + letrozole + Ox Ribociclib + fulvestrant + Ox Palbociclib + tamoxifen + Ox ç Abemaciclib + fulvestrant + Ox CDK4/6 inhibitor 77% Choice of endocrine therapy AI 59% Fulvestrant 32% Tamoxifen 8% Abemaciclib + letrozole + Ox Letrozole + Ox Anastrozole + Ox Tamoxifen + Ox Exemestane + Ox Other N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant tamoxifen and an LHRH agonist for an ER-positive, HER2-negative IDC but has now developed asymptomatic bone metastases 2 years after completing hormonal therapy. Which endocrine-based treatment would you most likely recommend? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Abemaciclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox Ribociclib + letrozole + Ox Palbociclib + tamoxifen + Ox ç CDK4/6 inhibitor 84% Choice of endocrine therapy AI 56% Fulvestrant 36% Tamoxifen 7% Abemaciclib + letrozole + Ox Abemaciclib + tamoxifen + Ox Anastrozole + Ox Exemestane + Ox Letrozole + Ox Tamoxifen + Ox Other N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant tamoxifen and an LHRH agonist 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? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Ribociclib + letrozole + Ox Palbociclib + fulvestrant + Ox Ribociclib + fulvestrant + Ox Abemaciclib + tamoxifen + Ox Abemaciclib + fulvestrant + Ox ç CDK4/6 inhibitor 82% Choice of endocrine therapy AI 63% Fulvestrant 23% Tamoxifen 13% Abemaciclib + letrozole + Ox Palbociclib + tamoxifen + Ox Letrozole + Ox Tamoxifen + Ox Exemestane + Ox Anastrozole + Ox Other N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant anastrozole and an LHRH agonist 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? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Ribociclib + fulvestrant + Ox Palbociclib + tamoxifen + Ox Abemaciclib + fulvestrant + Ox Ribociclib + letrozole + Ox Palbociclib + fulvestrant + Ox ç CDK4/6 inhibitor 86% Choice of endocrine therapy AI 43% Fulvestrant 35% Tamoxifen 21% Abemaciclib + tamoxifen + Ox Abemaciclib + letrozole + Ox Anastrozole + Ox Letrozole + Ox Tamoxifen + Ox Exemestane + Ox Other N = 100 US-based general medical oncologists

Palboiclib + fulvestrant + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + fulvestrant + Ox Ribociclib + letrozole + Ox

A 40-year-old premenopausal woman has completed 5 years of adjuvant anastrozole and an LHRH agonist 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? Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Ribociclib + letrozole + Ox Ribociclib + fulvestrant + Ox Abemaciclib + fulvestrant + Ox Palbociclib + tamoxifen + Ox ç CDK4/6 inhibitor 83% Choice of endocrine therapy AI 54% Fulvestrant 34% Tamoxifen 11% Abemaciclib + letrozole + Ox Abemaciclib + tamoxifen + Ox Letrozole + Ox Anastrozole + Ox Tamoxifen + Ox Exemestane + Ox Other N = 100 US-based general medical oncologists

Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + fulvestrant + Ox Palbociclib + letrozole + ovarian suppression/ablation (Ox) Palbociclib + letrozole + ovarian suppression/ablation (Ox) Abemaciclib + letrozole + Ox Ribociclib + letrozole + Ox

Toxicity and Tolerability Considerations with the Use of CDK4/6 Inhibitors

From a clinical perspective, how would you indirectly compare palbociclib, ribociclib and abemaciclib in terms of efficacy? They are equivalent in efficacy Abemaciclib is somewhat superior in efficacy Ribociclib is somewhat superior in efficacy Palbociclib is somewhat superior in efficacy N = 100 US-based general medical oncologists

They are equivalent in efficacy

From a clinical perspective, how would you indirectly compare palbociclib, ribociclib and abemaciclib in terms of general toxicity/tolerability? They are equivalent in terms of tolerability Palbociclib is somewhat more tolerable Abemaciclib is somewhat more tolerable Ribociclib is somewhat more tolerable Other N = 100 US-based general medical oncologists

They are equivalent in terms of tolerability Palbociclib is somewhat more tolerable Palbociclib and ribociclib are somewhat more tolerable Palbociclib is somewhat more tolerable Palbociclib has more neutropenia and abemaciclib has more GI toxicity Palbociclib and ribociclib are somewhat more tolerable

What is your best estimate of the likelihood that a patient who is receiving a CDK4/6 inhibitor in combination with endocrine therapy will require a dose reduction/delay or discontinuation? (Median) N = 100 US-based general medical oncologists

Palbociclib Ribociclib Abemaciclib 40% 40% 40% 40% 40% 40% 50% 50% 50% 35% 35% 45% 50% 50% 50% 25% 25% 25%

A 65-year-old woman has been started on a CDK4/6 inhibitor/letrozole for ER-positive, HER2-negative mBC. When would you first obtain blood counts? Palbociclib Ribociclib Abemaciclib N = 100 US-based general medical oncologists

Palbociclib Ribociclib Abemaciclib Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 and end of cycle 1 Day 15 cycle 1 and end of cycle 1 End of cycle 1

A 65-year-old woman who is receiving palbociclib/letrozole for ER-positive, HER2-negative mBC has an ANC of 350/mm3. What would be your most likely approach? Hold palbociclib until counts recover and restart at a lower dose Hold palbociclib until counts recover and restart at the same dose Lower palbociclib dose Continue palbociclib Switch to another therapy N = 100 US-based general medical oncologists

Hold palbociclib until counts recover and restart at the same dose Hold palbociclib until counts recover and restart at a lower dose Hold palbociclib until counts recover and restart at a lower dose Hold palbociclib until counts recover and restart at a lower dose Hold palbociclib until counts recover and restart at the same dose Hold palbociclib until counts recover and restart at the same dose

What is your best estimate for the risk of neutropenia requiring dose interruption or modification with… Median Palbociclib 30% Ribociclib 25% Abemaciclib 20% N = 100 US-based general medical oncologists

Palbociclib Ribociclib Abemaciclib 35% 35% 10% 50% 50% 20% 60% 50% 30-40% 34% 34% 10% 60% 60% 20% 25% 25% 10%

A 65-year-old woman has been started on a CDK4/6 inhibitor/letrozole for ER-positive, HER2-negative mBC. When would you first obtain liver function tests? Ribociclib Abemaciclib N = 100 US-based general medical oncologists

Ribociclib Abemaciclib Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 Day 15 cycle 1 End of cycle 1 End of cycle 1

When do you generally order electrocardiograms in your patients who are receiving ribociclib? Before beginning treatment only Before beginning treatment and on day 14 of cycle 1 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2 Before beginning treatment and at the beginning of cycle 2 Other Never N = 100 US-based general medical oncologists

Before beginning treatment and on day 14 of cycle 1 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2 Before beginning treatment and on day 14 of cycle 1 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2 Before beginning treatment, on day 14 of cycle 1 and at the beginning of cycle 2

In general, when you administer abemaciclib, do you initiate preemptive medication for gastrointestinal toxicity? N = 100 US-based general medical oncologists

No No Yes No No Yes

A 65-year-old woman who is receiving abemaciclib/letrozole for ER-positive, HER2-negative mBC develops Grade 2 diarrhea, which resolves within 12 hours. What would be your most likely approach? Continue abemaciclib Lower abemaciclib dose Hold abemaciclib and restart at the same dose Hold abemaciclib and restart at a lower dose Switch to another therapy Other N = 100 US-based general medical oncologists

Continue abemaciclib Continue abemaciclib Continue abemaciclib Continue abemaciclib Continue abemaciclib Continue abemaciclib

A 65-year-old woman who is receiving abemaciclib/letrozole for ER-positive, HER2-negative mBC develops Grade 2 diarrhea, which resolves within 48 hours. What would be your most likely approach? Continue abemaciclib Lower abemaciclib dose Hold abemaciclib and restart at the same dose Hold abemaciclib and restart at a lower dose Switch to another therapy Other N = 100 US-based general medical oncologists

Hold abemaciclib and restart at the same dose Continue abemaciclib Hold abemaciclib and restart at the same dose Hold abemaciclib and restart at the same dose Hold abemaciclib and restart at the same dose Hold abemaciclib and restart at a lower dose Continue abemaciclib

In a patient with bone marrow involvement and moderate cytopenias to whom you were planning to administer a CDK4/6 inhibitor, would you have any preference as to which agent to use (in addition to any other systemic or local therapy that you would like to include)? Yes, abemaciclib Yes, palbociclib Yes, ribociclib Yes, palbociclib or ribociclib No N = 100 US-based general medical oncologists

Yes, abemaciclib Yes, abemaciclib Yes, abemaciclib Yes, abemaciclib Yes, abemaciclib Yes, abemaciclib

In a patient who has recently completed radiation therapy to the hip because of a pathologic fracture to whom you were planning to administer a CDK4/6 inhibitor, would you have any preference as to which agent to use (in addition to any other systemic or local therapy that you would like to include)? Yes, palbociclib Yes, palbociclib or ribociclib Yes, abemaciclib Yes, ribociclib No N = 100 US-based general medical oncologists

No No No Yes, palbociclib Yes, abemaciclib Yes, palbociclib

In a patient with irritable bowel syndrome to whom you were planning to administer a CDK4/6 inhibitor, would you have any preference as to which agent to use (in addition to any other systemic or local therapy that you would like to include)? Yes, palbociclib Yes, ribociclib Yes, palbociclib or ribociclib Yes, abemaciclib No N = 100 US-based general medical oncologists

Yes, palbociclib or ribociclib

In a patient with coronary artery disease to whom you were planning to administer a CDK4/6 inhibitor, would you have any preference as to which agent to use (in addition to any other systemic or local therapy that you would like to include)? Yes, palbociclib Yes, ribociclib Yes, palbociclib or ribociclib Yes, abemaciclib No N = 100 US-based general medical oncologists

Yes, palbociclib No Yes, palbociclib Yes, palbociclib No

Have you switched or would you switch to another CDK4/6 inhibitor for a patient who experiences toxicity/tolerability problems with one CDK4/6 inhibitor? I haven't and would not I haven't but would for the right patient I have N = 100 US-based general medical oncologists

I haven't but would for the right patient

Based on your personal experience, do you believe patients are more likely to be adherent to a regimen that is administered continuously as opposed to 3 weeks on, 1 week off? N = 100 US-based general medical oncologists

No No No Yes Yes Yes

Putting financial issues aside, approximately what proportion of your patients receiving CDK4/6 inhibitors have significant issues with adherence? Median Palbociclib 15% Ribociclib 18% Abemaciclib N = 100 US-based general medical oncologists

Palbociclib Ribociclib Abemaciclib 10% Not enough experience with this agent Not enough experience with this agent 10% Not enough experience with this agent 5% <10% Not enough experience with this agent 20% 0% Not enough experience with this agent Not enough experience with this agent 15% 15% 10% 10% Not enough experience with this agent Not enough experience with this agent

In addition to systemic therapy for breast cancer, what is your best estimate of the number of other medications your patients with metastatic disease of the following age ranges are receiving on average?  Age 40-49 50-59 60-69 70-79 80-89 No. of medications (median) 2 3 4 5 N = 100 US-based general medical oncologists

40-49 50-59 60-69 70-79 80-89 1 1 2 3 3 1-2 2-3 3-4 3-4 3 4 5 8 8 1-2 2-5 2-5 5-8 5-10 2 3 4 5 6 1 2 2 3 3

Impact of Extent and Site(s) of Disease (Including CNS) on Clinical Decision-Making

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with extensive moderately symptomatic hepatic metastases with normal liver function 2 years after starting adjuvant anastrozole. What would be your most likely treatment approach? Chemotherapy  endocrine therapy + CDK4/6 inhibitor Endocrine therapy + CDK4/6 inhibitor Chemotherapy  endocrine therapy Endocrine therapy alone N = 100 US-based general medical oncologists

Endocrine therapy + CDK4/6 inhibitor

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with extensive moderately symptomatic hepatic metastases with normal liver function 2 years after starting adjuvant anastrozole. What would be your most likely endocrine therapy strategy? ç CDK4/6 inhibitor 85% Choice of endocrine therapy AI 27% Fulvestrant 67% Tamoxifen 6% N = 100 US-based general medical oncologists

Abemaciclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Abemaciclib + fulvestrant Fulvestrant

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with extensive moderately symptomatic hepatic metastases with abnormal LFTs 2 years after starting adjuvant anastrozole. What would be your most likely overall treatment approach? Chemotherapy  endocrine therapy + CDK4/6 inhibitor Endocrine therapy + CDK4/6 inhibitor Chemotherapy  endocrine therapy Endocrine therapy alone N = 100 US-based general medical oncologists

Chemotherapy  endocrine therapy + CDK4/6 inhibitor If mildly elevated, Endocrine therapy + CDK4/6 inhibitor; if significantly elevated, Chemotherapy  endocrine therapy + CDK4/6 inhibitor Chemotherapy  endocrine therapy + CDK4/6 inhibitor

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with extensive moderately symptomatic hepatic metastases with abnormal LFTs 2 years after starting adjuvant anastrozole. What would be your most likely endocrine therapy strategy? ç CDK4/6 inhibitor 80% Choice of endocrine therapy AI 24% Fulvestrant 71% Tamoxifen 4% N = 100 US-based general medical oncologists

Palbociclib + fulvestrant Abemaciclib + fulvestrant Fulvestrant

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with a single brain metastasis 2 years after starting adjuvant anastrozole. The brain metastasis is resected, and the patient has no other sites of disease. What would be your most likely overall treatment approach? Radiation therapy (XRT)  endocrine therapy + CDK4/6 inhibitor Endocrine therapy + CDK4/6 inhibitor Chemotherapy  endocrine therapy + CDK4/6 inhibitor XRT  endocrine therapy alone Endocrine therapy alone Chemotherapy + XRT  endocrine therapy Chemotherapy + XRT  endocrine therapy + CDK4/6 inhibitor Chemotherapy  endocrine therapy N = 100 US-based general medical oncologists

Radiation therapy (XRT)  endocrine therapy + CDK4/6 inhibitor XRT  endocrine therapy alone XRT  endocrine therapy alone Endocrine therapy alone

A 65-year-old woman with ER-positive, HER2-negative, node-negative breast cancer presents with a single brain metastasis 2 years after starting adjuvant anastrozole. The brain metastasis is resected, and the patient has no other sites of disease. What would be your most likely endocrine therapy strategy? ç CDK4/6 inhibitor 72% Choice of endocrine therapy AI 42% Fulvestrant 51% Tamoxifen 4% N = 100 US-based general medical oncologists

Abemaciclib + fulvestrant Letrozole Fulvestrant Continue anastrozole

Based on current clinical trial data and your personal experience, how would you generally compare the likelihood that a patient with ER-positive, HER2-negative mBC will experience a meaningful response with a CDK4/6 inhibitor in combination with endocrine therapy as opposed to chemotherapy? About the same Greater chance of response with CDK4/6 inhibitor/endocrine therapy Greater chance of response with chemotherapy I don't know N = 100 US-based general medical oncologists

Greater chance of response with CDK4/6 inhibitor/endocrine therapy About the same About the same Greater chance of response with CDK4/6 inhibitor/endocrine therapy Greater chance of response with CDK4/6 inhibitor/endocrine therapy Greater chance of response with CDK4/6 inhibitor/endocrine therapy About the same

Based on current clinical trial data and your personal experience, how would you compare the rapidity of response with a CDK4/6 inhibitor in combination with endocrine therapy as opposed to chemotherapy in patients with ER-positive, HER2-negative mBC? About the same More rapid response with CDK4/6 inhibitor/ endocrine therapy More rapid response with chemotherapy I don't know N = 100 US-based general medical oncologists

More rapid response with chemotherapy About the same More rapid response with chemotherapy About the same More rapid response with chemotherapy More rapid response with chemotherapy More rapid response with chemotherapy

In patients for whom you include chemotherapy as a component of first-line therapy for ER-positive, HER2-negative mBC, do you generally administer hormonal therapy concurrently with the chemotherapy or sequentially after its completion? In patients for whom you include chemotherapy as a component of first-line therapy for ER-positive, HER2-negative mBC, how long do you generally administer the chemotherapy? A defined number of cycles Until the patient improves Until disease progression or intolerable side effects/toxicity Other Median no. of patients who received chemotherapy as a component of first-line therapy for ER-positive, HER2-negative mBC in the past year = 10 N = 100 US-based general medical oncologists

Sequentially Sequentially Sequentially Sequentially Sequentially In patients for whom you include chemotherapy as a component of first-line therapy for ER-positive, HER2-negative mBC, do you generally administer hormonal therapy concurrently with the chemotherapy or sequentially after its completion? Sequentially Sequentially Sequentially Sequentially Sequentially Sequentially

Until disease progression or intolerable side effects/toxicity In patients for whom you include chemotherapy as a component of first-line therapy for ER-positive, HER2-negative mBC, how long do you generally administer the chemotherapy? Until disease progression or intolerable side effects/toxicity Until disease progression or intolerable side effects/toxicity A defined number of cycles Until the patient improves Until disease progression or intolerable side effects/toxicity A defined number of cycles

Treatment Strategies for Patients with Disease Progression on a CDK4/6 Inhibitor; Ongoing Clinical Trials

What is your usual next endocrine therapy for a 60-year-old woman who received palbociclib/letrozole as first-line therapy for de novo ER-positive, HER2-negative mBC and now has disease progression? Fulvestrant Everolimus + exemestane Everolimus + fulvestrant Exemestane Continue palbociclib and switch ET fulvestrant Another CDK4/6 inhibitor +/- ET N = 100 US-based general medical oncologists

Everolimus + exemestane or everolimus + fulvestrant

What is your usual next endocrine therapy for a 60-year-old woman with ER-positive, HER2-negative mBC who received adjuvant anastrozole and then palbociclib/fulvestrant at the time of recurrence and now has disease progression? Everolimus + exemestane 60% Exemestane Everolimus + fulvestrant Another CDK4/6 inhibitor +/- ET Other N = 100 US-based general medical oncologists

Everolimus + exemestane Everolimus + fulvestrant Everolimus + exemestane Everolimus + exemestane Everolimus + exemestane

Have you or would you continue a CDK4/6 inhibitor beyond disease progression for patients with ER-positive, HER2-negative mBC outside of a clinical trial?  I haven't and would not I haven't but would for the right patient I have N = 100 US-based general medical oncologists

I haven't but would for the right patient I haven't and would not I haven't and would not I haven't but would for the right patient I haven't and would not I haven't and would not I haven't and would not

At what point, if any, do you generally order multiplex testing such as next-generation sequencing in your patients with ER-positive, HER2-negative mBC? At initial diagnosis of metastatic disease After first-line therapy After second-line therapy After third-line therapy or beyond I do not order multiplex testing in patients with ER-positive, HER2-negative mBC N = 100 US-based general medical oncologists

After second-line therapy At initial diagnosis of metastatic disease At initial diagnosis of metastatic disease At initial diagnosis of metastatic disease At initial diagnosis of metastatic disease After third-line therapy or beyond

Which therapy, if any, would you not administer to a patient with ER-positive, HER2-negative mBC and an ESR1 mutation? (Select all that apply.) An aromatase inhibitor Tamoxifen Fulvestrant Ovarian suppression/ablation A CDK4/6 inhibitor I don't know N = 100 US-based general medical oncologists

An aromatase inhibitor

Use of CDK4/6 Inhibitors in Special Situations (Male Patients, HER2-Positive Disease, Local Recurrence, Significant Residual Disease After Neoadjuvant Therapy)

What would be your likely initial systemic therapy for a 60-year-old patient presenting with de novo ER-positive, HER2-positive mBC with asymptomatic bone metastases? Endocrine therapy + trastuzumab Endocrine therapy + trastuzumab + pertuzumab Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab maintenance Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab + endocrine therapy maintenance Endocrine therapy alone Chemotherapy + trastuzumab  trastuzumab maintenance Chemotherapy + trastuzumab  trastuzumab + endocrine therapy maintenance Other N = 100 US-based general medical oncologists

ET + T/P or chemo + T/P  TP, depending on extent of bone lesions Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab + endocrine therapy maintenance ET + T/P or chemo + T/P  TP, depending on extent of bone lesions Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab + endocrine therapy maintenance Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab maintenance Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab + endocrine therapy maintenance Chemotherapy + trastuzumab + pertuzumab  trastuzumab + pertuzumab + endocrine therapy maintenance

Have you or would you administer a CDK4/6 inhibitor to a patient with HER2-positive mBC off protocol? I haven't and would not I haven't but would for the right patient I have N = 100 US-based general medical oncologists

I haven't but would for the right patient I haven't and would not I haven't and would not I have I haven't and would not I haven't and would not I haven't but would for the right patient

What would be your likely next systemic therapy for a 60-year-old woman with ER-positive, HER2-positive mBC who responds to paclitaxel/trastuzumab/pertuzumab followed by maintenance with trastuzumab/pertuzumab and anastrozole and now has disease progression? T-DM1 T-DM1 + fulvestrant T-DM1 + fulvestrant + CDK4/6 inhibitor T-DM1 + other endocrine therapy T-DM1 + other endocrine therapy + CDK4/6 inhibitor Reinitiate paclitaxel/ trastuzumab/pertuzumab Other N = 100 US-based general medical oncologists

T-DM1 T-DM1 T-DM1 T-DM1 T-DM1 T-DM1

Which of the following would you most likely recommend? A 65-year-old man presents with de novo ER-positive, HER2-negative mBC with asymptomatic bone metastases. Would you administer an LHRH agonist? Which of the following would you most likely recommend? ç CDK4/6 inhibitor 44% Choice of endocrine therapy AI 38% Fulvestrant Tamoxifen 18% N = 100 US-based general medical oncologists

Would you administer an LHRH agonist? Yes No No No No No

Palbociclib + letrozole Which of the following would you most likely recommend? Palbociclib + letrozole Tamoxifen Palbociclib + tamoxifen Palbociclib + fulvestrant Abemaciclib + tamoxifen Ribociclib + tamoxifen

Which of the following would you most likely recommend? A 65-year-old man with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 2 years after starting adjuvant anastrozole/LHRH agonist. Would you administer an LHRH agonist? Which of the following would you most likely recommend? ç CDK4/6 inhibitor 74% Choice of endocrine therapy AI 24% Fulvestrant 66% Tamoxifen 8% N = 100 US-based general medical oncologists

Would you administer an LHRH agonist? Yes No Yes No Yes No

Palbociclib + fulvestrant Which of the following would you most likely recommend? Palbociclib + fulvestrant Tamoxifen Palbociclib + fulvestrant Palbociclib + fulvestrant Palbociclib + fulvestrant Ribociclib + tamoxifen

Which of the following would you most likely recommend? A 65-year-old man with ER-positive, HER2-negative, node-negative breast cancer has developed asymptomatic bone metastases 2 years after starting adjuvant tamoxifen/LHRH agonist.                         Would you administer an LHRH agonist? Which of the following would you most likely recommend? ç CDK4/6 inhibitor 75% Choice of endocrine therapy AI 43% Fulvestrant 53% Tamoxifen 0% N = 100 US-based general medical oncologists

Would you administer an LHRH agonist? Yes Yes Yes No Yes Yes

Palbociclib + letrozole Which of the following would you most likely recommend? Palbociclib + letrozole Letrozole Palbociclib + letrozole Palbociclib + fulvestrant Palbociclib + letrozole Palbociclib + letrozole

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with multiple positive nodes involved at primary surgery outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with locally advanced but potentially resectable disease outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not I haven’t and would not I have I haven’t but would for the right patient I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient who desires breast conservation but for whom significant tumor shrinkage is required in order to achieve this outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t and would not I haven’t and would not I haven’t and would not I have I haven’t and would not I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with inflammatory breast cancer outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t but would for the right patient I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with significant residual disease in the breast and nodes after neoadjuvant chemotherapy outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with significant residual disease in the breast and nodes after neoadjuvant endocrine therapy outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient who has had an isolated lung metastasis removed (no other sites of disease) outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not I haven’t but would for the right patient I haven’t but would for the right patient

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient who has had an isolated brain metastasis removed (no other sites of disease) outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not I haven’t but would for the right patient I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient with an isolated local recurrence in the breast after prior breast-conserving surgery (no other sites of disease) who is now s/p mastectomy outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not I haven’t and would not I have I haven’t but would for the right patient I haven’t and would not I haven’t and would not

Have you or would you administer a CDK4/6 inhibitor in combination with endocrine therapy to a patient who has had an isolated local recurrence in the chest wall removed after prior mastectomy (no other sites of disease) outside of a clinical trial setting?  I haven’t and would not I haven’t but would for the right patient I have N = 100 US-based general medical oncologists

I haven’t but would for the right patient I haven’t and would not