MODULE 1: Adjuvant and Neoadjuvant Therapy for HER2-Positive Breast Cancer (BC) — Dr Winer

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• A 60-year-old patient presents with a palpable 1.8-cm, ER/PR-negative, HER2-positive infiltrating ductal carcinoma (IDC) with a clinically negative axilla. Would you generally recommend neoadjuvant systemic therapy (NST) in this situation? If so, what specific regimen would you use? What if the patient’s tumor were 2.4 centimeters?
• When using pertuzumab as a component of NST, do you ever continue it postoperatively? Currently, do you ever recommend pertuzumab as part of adjuvant treatment for a patient who did not receive it as a component of NST? Do you believe the results of the Phase III APHINITY trial will significantly affect the frequency with which you employ pertuzumab in the adjuvant setting?
• In which clinical situations do you use additional systemic therapy for patients with HER2-positive BC who have residual disease after completing NST?
• A 45-year-old woman is s/p lumpectomy for an ER/PR-negative, HER2-positive IDC with 3 positive nodes. Regulatory and reimbursement issues aside, would you consider adding neratinib after the completion of adjuvant chemotherapy/trastuzumab?

Faculty Presentation Topics

• Known risks and benefits associated with the use of neoadjuvant pertuzumab for patients with HER2-positive and ER-negative or ER-positive disease
• Results and clinical implications of the Phase III APHINITY trial comparing adjuvant chemotherapy/trastuzumab to chemotherapy/trastuzumab/pertuzumab for HER2-positive early BC (EBC)
• Ongoing studies of novel HER2-targeted therapies in the neoadjuvant and adjuvant settings (ATEMPT, KATHERINE, KAITLIN, et cetera)
• Available data with and potential clinical role of neratinib as extended adjuvant therapy

MODULE 2: Use of Genomic Assays and Biomarkers to Assist in the Management of ER-Positive EBC — Dr Gralow

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• A 60-year-old patient is s/p breast-conserving treatment for a Grade 1, 0.8-cm, ER-positive, HER2-negative, node-negative IDC. In general, would you likely order a genomic tumor assay in this situation, and if so, which one? What if the tumor were 1.4 centimeters? 3.2 centimeters?
• A 65-year-old patient is diagnosed with a 1.4-cm, ER-positive, HER2-negative IDC. She has 1 positive sentinel node. In general, would you order a genomic assay for this patient, and if so, which one? What if the patient were premenopausal? What if she had 3 positive lymph nodes?
• A 65-year-old woman with a 1.5-cm, ER-positive, HER2-negative IDC and 2 positive nodes receives TC x 4 followed by anastrozole for 5 years. A genomic assay has never been ordered. The patient has tolerated anastrozole well and has normal bone density. Would you likely continue the anastrozole? Would you order a genomic assay to help inform this decision?

Faculty Presentation Topics

• Recent data sets informing the use of molecular profiling to personalize adjuvant therapy for patients with ER-positive EBC
• Clinical investigator perspectives on published guidelines and consensus statements (ASCO, St Gallen, et cetera) regarding the current role of genomic assays in decision-making for patients with node-negative and node-positive, ER-positive EBC
• Available data with and potential clinical role of genomic assays to guide the use of neoadjuvant therapy

MODULE 3: Selection and Sequence of Therapy for Patients with ER-Positive, HER2-Negative Metastatic BC (mBC) — Dr Blackwell

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• What would you generally recommend for a 65-year-old postmenopausal woman who presents with de novo asymptomatic ER-positive, HER2-negative BC metastatic to the bone? What if she had bone and liver involvement? What if the patient were 45 (premenopausal)?
• What would you generally recommend for a 65-year-old postmenopausal woman who experiences relapse with asymptomatic ER-positive, HER2-negative BC metastatic to the bone 3 years into adjuvant anastrozole? How, if at all, would you alter your treatment approach if this patient completed 5 years of anastrozole and relapse occurred 2 years later?
• What has been your clinical experience with ribociclib and abemaciclib? From an activity and tolerability standpoint, how do you believe these agents compare to palbociclib? Does the single-agent activity observed with abemaciclib mean it is a more potent CDK4/6 inhibitor than palbociclib or ribociclib?
• A postmenopausal woman completes 5 years of adjuvant anastrozole for an ER-positive, HER2-negative IDC but develops biopsy-proven bone metastases 2 years later. She receives palbociclib combined with letrozole and responds, but 1 year later experiences asymptomatic disease progression. What would be your likely next treatment?

Faculty Presentation Topics

• Patient- and disease-related factors affecting the selection of therapy for ER-positive, HER2-negative mBC
• Comparative activity, side effects and CNS penetration of available and investigational CDK4/6 inhibitors
• Results of the Phase III MONALEESA-2 trial of ribociclib/letrozole compared to letrozole alone for postmenopausal patients with newly diagnosed ER-positive advanced BC; recent FDA approval of the combination
• Results from the MONARCH 1 and 2 studies of abemaciclib; potential role of abemaciclib in clinical practice

MODULE 4: Long-Term Management of HER2-Positive mBC — Dr Pegram

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• How do you currently approach the choice of first-line therapy for patients who experience relapse after receiving pertuzumab in either the neoadjuvant or adjuvant setting?
• Are there any situations in which you use endocrine therapy alone as first-line therapy for patients with ER-positive, HER2-positive (triple-positive) mBC? Have any specific hormonal interventions proven more effective in patients with triple-positive disease? Would it be reasonable to administer trastuzumab/pertuzumab with an aromatase inhibitor without chemotherapy for certain patients with triple-positive disease?
• What is known about the activity of CDK4/6 inhibitors in patients with HER2-positive disease? Outside of a clinical trial, are there any situations in which you would use palbociclib in the management of triple-positive mBC?
• What would be your usual third- and fourth-line treatment recommendations for a patient with HER2-positive mBC who has received trastuzumab/pertuzumab/docetaxel (THP) followed by T-DM1?
• A patient receives 6 cycles of THP for HER2-positive mBC and experiences a clinical complete response. During maintenance therapy with trastuzumab/pertuzumab, multiple small brain metastases are noted with no evidence of systemic disease. In addition to local therapy to the brain, what would be your most likely systemic therapy?

Faculty Presentation Topics

• Published research data examining the use of combined endocrine and anti-HER2 blockade (PERTAIN, ALTERNATIVE, et cetera) for patients with triple-positive mBC
• Optimal therapeutic approach for patients with HER2-positive brain metastases
• Other novel agents and strategies under development for patients with HER2-positive mBC (neratinib, margetuximab, ONT-380, CDK4/6 inhibitors, et cetera)
• Incidence and clinical significance of HER2 mutations and rational nonprotocol treatment options

MODULE 5: Potential Role of PARP Inhibition in the Management of BC — Dr Nanda

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• For what specific clinical situations do you order BRCA mutation testing for your patients with BC? What assay or multigene panel do you generally consult for this purpose?
• How frequently are BRCA mutations observed in patients with ER-positive BC? Do PARP inhibitors behave differently in these patients than in those with triple-negative disease?
• Do you generally recommend bilateral oophorectomy for patients identified with a BRCA1 or 2 mutation? If yes, at what age? What about a hysterectomy? Do you generally recommend any further surveillance for other cancers?
• Curently, are there situations in which you would recommend olaparib to a patient with BRCA-positive mBC outside of a clinical trial setting?
• Is there any reason to believe that BC with a somatic BRCA mutation might manifest differently than BC with a germline mutation?
• In addition to BRCA, are there any other germline/somatic mutations or genomic signatures that might be predictive biomarkers for PARP inhibition in patients with BC?

Faculty Presentation Topics

• Indications for BRCA mutation testing in patients with BC and implications of a BRCA1/2 mutation for protocol and nonprotocol treatment planning
• Available screening assays/multigene panels to detect BRCA mutations or other genetic signatures that may predict sensitivity to PARP inhibition
• Results of the Phase III OlympiAD study comparing olaparib to chemotherapy for patients with HER2-negative mBC and a germline BRCA mutation
• Early activity and safety of other PARP inhibitors in patients with mBC; design, eligibility criteria and expected completion dates for Phase III trials

MODULE 6: Novel Agents and Strategies Under Active Investigation in BC — Dr Rugo

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS

• Have you requested next-generation sequencing for 1 or more of your patients with mBC? If so, what molecular alterations were observed and how did this information guide clinical trial opportunities and/or off-protocol care?
• What is the incidence of androgen receptor (AR) overexpression in patients with mBC? Does this vary based on ER status? Have you administered an antiandrogen to 1 or more patients as part of or outside a clinical trial setting? If so, have you observed clinical responses to these agents?
• What is the incidence of PD-L1 expression in patients with mBC? Do you believe PD-L1 is the appropriate biomarker to evaluate for potential responsiveness to immune checkpoint inhibitor therapy in BC? If not, what do you believe is the biologic rationale for the responses observed in patients with mBC?
• Are there situations in which you would recommend treatment with one of the approved anti-PD-1/PD-L1 compounds to a patient with BC outside of a clinical trial setting?
• What other novel agents or strategies under development appear particularly promising for patients with HER2-negative mBC?

Faculty Presentation Topics

• Available clinical trial data documenting the presence of genomic alterations in BC and potential benefit of targeted therapies
• Biologic rationale for, available research data with and ongoing evaluation of antiandrogen therapy for patients with “AR-positive” disease
• Activity and duration of response with anti-PD-1/PD-L1 antibodies in patients with mBC
• Ongoing studies evaluating anti-PD-1/PD-L1 antibodies alone or in combination with other systemic therapies in BC