1 Empowering Nurses to Improve the Care of Patients With Metastatic Breast CancerThis program is supported by educational grants from Celgene Corporation, Genentech, and Lilly.
2 Core Faculty Kathy A. Pratt, BSN, RN, OCN, CBCN Breast Patient Navigator Harold C. Simmons Comprehensive Cancer Center University of Texas Southwestern Medical Center Dallas, Texas Lillie D. Shockney, RN, BS, MAS University Distinguished Service Professor of Breast Cancer Professor Departments of Surgery, Oncology, Gynecology John Hopkins University School of Medicine Administrative Director, Breast Center and Cancer Survivorship Programs Department of Surgery and Oncology Johns Hopkins Baltimore, Maryland This slide lists the faculty who were involved in the production of these slides.
3 Faculty Disclosures Kathy A. Pratt, BSN, RN, OCN, CBCN, has no real or apparent conflicts of interest to report. Lillie D. Shockney, RN, BS, MAS, has no real or apparent conflicts of interest to report.
4 Agenda Metastatic Breast Cancer Overview Case 1: Triple-Negative MBCCase 2: ER+ BC With Distant Recurrence After Extended Adjuvant Therapy Case 3: ER/PgR-Positive BC With Progression After 1 Yr of Hormonal Therapy Case 4: HER2+ MBC and Progression on Trastuzumab Regimen Supportive Care BC, breast cancer; ER, estrogen receptor; MBC, metastatic breast cancer; PgR, progesterone receptor.
5 Metastatic Breast Cancer Overview
6 Therapy Stratification for Metastatic Breast CancerA clinical trial is recommended as the first option in treating pts with cancer Metastatic disease at presentation/first recurrence of disease should be biopsied as part of workup Ensures accurate tumor histology to confirm MBC vs new primary cancer and biomarker determination Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
7 Therapy Stratification for Metastatic Breast CancerInitial stratification Presence of bone metastasis (metastases?) or not Tumor hormone receptor status HER2 status In pts with systemic disease or de novo stage IV, if bone disease is present, provide supportive therapy for bone disease before treating, based on ER, PgR, HER2 status and endocrine responsiveness ER, estrogen receptor; PgR, progesterone receptor. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
8 Endocrine Therapy vs Chemotherapy in MBCTreatments associated with minimal toxicity preferred Endocrine therapy (alone or in combination) should be used as initial treatment except in cases of immediately life-threatening disease Patients whose tumors express any level of hormone receptors should be offered endocrine therapy Treatment recommendations should be based on type of adjuvant treatment, disease-free interval, and organ function Sequential endocrine therapy preferred treatment for most women with hormone receptor–positive metastatic breast cancer Menopausal status assessment critical; ovarian suppression or ablation should be used in premenopausal women MBC, metastatic breast cancer. Rugo HS, et al. J Clin Oncol. 2016;[Epub ahead of print]. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
9 Endocrine Therapy for Recurrent or Stage IV DiseaseRegimen Premenopausal Pts Selective ER modulators or ovarian ablation/suppression plus endocrine therapy as for postmenopausal women Postmenopausal Pts Nonsteroidal AI or steroidal aromatase inactivator Tamoxifen or toremifene Exemestane + everolimus Megestrol acetate Palbociclib + letrozole Fluoxymesterone Palbociclib + fulvestrant (Category 1) Ethinyl estradiol Fulvestrant AI, aromatase inhibitor; ER, estrogen receptor. All agents are Category 2A recommendations unless otherwise indicated. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
10 Recommended Use of Chemotherapy in Hormone Receptor–Positive MBCExperts do NOT recommend chemotherapy based solely on the presence of asymptomatic visceral involvement and/or a short disease-free interval after adjuvant therapy Experts recommend chemotherapy for: Visceral crisis: severe organ dysfunction based on symptoms, laboratory assessment, and rapid progression (eg, lymphangitic lung metastases, bone marrow replacement, carcinomatous meningitis, or significant liver metastases) Progression following multiple lines of endocrine therapy MBC, metastatic breast cancer. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
11 Appropriate Chemotherapy DosingUse of sequential single agents lowers frequency of required dose reductions Combination chemotherapy: Produces higher ORR, longer TTP vs single-agent chemotherapy Demonstrates increased toxicity, small survival benefit Not found to be superior to sequential single agents Continue first-line chemotherapy until progression TTP, time to progression. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
12 Single Agents for Recurrent or Metastatic Breast CancerPreferred Agents Other Agents Anthracyclines: doxorubicin, pegylated liposomal doxorubicin Antimetabolites: capecitabine, gemcitabine Other microtubule inhibitors: vinorelbine, eribulin Taxanes: paclitaxel Carboplatin Cisplatin Cyclophosphamide Docetaxel Epirubicin Ixabepilone Nab-paclitaxel All agents are Category 2A recommendations. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
13 Chemotherapy Combinations for Recurrent or Metastatic Breast CancerRegimen AC (doxorubicin/cyclophosphamide) CAF/FAC (cyclophosphamide/doxorubicin/fluorouracil) CMF (cyclophosphamide/methotrexate/fluorouracil) Docetaxel/capecitabine EC (epirubicin/cyclophosphamide) FEC (fluorouracil/epirubicin/cyclophosphamide) Gemcitabine/carboplatin GT (gemcitabine/paclitaxel) Paclitaxel/bevacizumab All agents are Category 2A recommendations. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
14 Factors Influencing Chemotherapy Choice in MBC: Tumor BurdenSequential single-agent chemotherapy appropriate for pts with low tumor burden, lack of cancer-specific symptoms Less toxic, lower risk of progression, similar OS vs combination chemotherapy[1] Combination chemotherapy useful in pts with large tumor burden, rapid progression, or symptomatic disease Higher response rate vs single-agent chemotherapy[1] Individualize therapy for pts with brain metastases; may not need systemic therapy if disease remains localized[2] MBC, metastatic breast cancer. 1. Dear RF, et al. Cochrane Database Syst Rev. 2013:CD 2. Arslan C, et al. Expert Opin Pharmacother. 2010;11: Slide credit: clinicaloptions.com
15 Paclitaxel vs Nab-Paclitaxel in MBC: PFS1.00 Nab-paclitaxel (n = 229) Paclitaxel (n = 224) P = .006 0.75 PFS (Proportion of Pts) 0.50 0.25 MBC, metastatic breast cancer. 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 Wk Slide credit: clinicaloptions.com Gradishar W, et al. J Clin Oncol. 2005;23:
16 Paclitaxel vs Nab-Paclitaxel in MBC: Adverse Events100 Nab-paclitaxel 260 mg/m2 Paclitaxel 175 mg/m2 80 60 Pts (%) 40 20 ANC, absolute neutrophil count; MBC, metastatic breast cancer. Alopecia Fatigue Neutropenia Arthralgia Myalgia Nausea Diarrhea Sensory Neuropathy Infection w/ Unknown ANC Slide credit: clinicaloptions.com Gradishar W, et al. J Clin Oncol. 2005;23:
17 Factors Influencing Chemotherapy Choice in MBC: Pt PreferenceTreatment Greater likelihood of treatment response, despite toxicity Select combination therapy vs single agent Lower risk of specific AEs Peripheral neuropathy: avoid taxanes Cardiotoxicity: avoid anthracyclines Less interruption of daily life Select oral agent vs IV infusion Choose reduced IV treatment frequency AE, adverse event; MBC, metastatic breast cancer. Slide credit: clinicaloptions.com
18 Single Agent Considerations Combination Regimen ConsiderationsFactors Influencing Chemotherapy Choice in MBC: Health or Performance Status Pts with poor PS or significant comorbidities may not benefit from treatment Single Agent Considerations Anthracyclines Avoid if history of HF, CVD Oral therapies Avoid in pts with: Symptomatic peritoneal disease Difficulty swallowing pills Unable to follow regimen instructions Agents requiring premedication Avoid in pts at risk for hyperglycemia (diabetics) or steroid intolerant Benefits and risks of single-agent therapy should be balanced against overall prognosis Combination Regimen Considerations Prior treatment and toxicities Myelosuppression with prior therapy that resulted in modification or delays Microtubulin-targeted agents Avoid in pts with baseline or history grade 3/4 neuropathy Anthracycline regimen Good for chemotherapy-naive pts or without previous anthracycline Anthracyclines Avoid in pts with cardiac history CVD, cardiovascular disease; HF, heart failure; MBC, metastatic breast cancer; PS, performance status. Slide credit: clinicaloptions.com
19 Triple-Negative MBC MBC, metastatic breast cancer.
20 Case 1: Triple-Negative MBCMs Smith, premenopausal 38-yr-old black woman, initially diagnosed 2 yrs earlier with clinical stage IIB, T2N0M0 triple-negative right breast cancer She had PR to neoadjuvant chemotherapy (ddAC → wT), with final pathologic staging stage IIA, T1N0(sn)M0 She now presents with pain in hip and lower back and shortness of breath on exertion MBC, metastatic breast cancer. Slide credit: clinicaloptions.com
21 Case 1: Triple-Negative MBCLabs: CBC, WNL; CMP, WNL except for alkaline phosphatase 365 IU/L; SGOT 157 U/L; SGPT U/L; CA U/mL Pathology: liver biopsy (to confirm MBC histology and rerun breast prognostic panel) confirmed invasive ductal carcinoma, grade 3; ER negative; PgR negative; HER2 (IHC) 2+/equivocal; HER2 (FISH) nonamplified; Ki-67 80% Diagnostic imaging: bone scan positive for lesions in the lumbar spine and right hip; CT scan chest/ abdomen/pelvis shows 2 hypoechoic hepatic lesions (2.2 cm, 1.5 cm) and 1.5-cm nodule left lower lung CBC, complete blood count; CMP, complete metabolic profile; ER, estrogen receptor; MBC, metastatic breast cancer; PgR, progesterone receptor; WNL, within normal limits. Labs: CBC--WNL; CMP–WNL except for alkaline phosphatase 365 IU/L (normal IU/L); SGOT 157 U/L (normal 5-40 U/L); SGPT 326 U/L (normal 5-40 U/L). CA15-3: 225 U/ml (normal <30 U/ml) Slide credit: clinicaloptions.com
22 Pt Barriers to Care Pt reported she was told that she was “cured” after her initial diagnosis and treatment in 2014 Uncertain if she now has breast cancer or 3 cancers since it has spread to bone and lung Pt has a new job as of 3 mos ago and is worried that she will lose job and her health insurance She has a 12-yr-old daughter and 9-yr-old son She is worried that her husband will “not be able to raise the children” if she were to die Pt said that she “has to live to be here for her children” Slide credit: clinicaloptions.com
23 Barrier Assessment by Nurse NavigatorFear: makes it difficult to make rational decisions Financial: has virtually no PTO at work, as she is a new employee and just completed her 90-day probationary period; has a prescription card for medication, but the copay is $50 per prescription Transportation: takes public transportation to work but owns a car; would not have money for hospital parking because of tight budget Lack of clinical understanding/need for pt education: she thought her clinician told her that she had breast cancer and bone cancer and lung cancer; she, therefore, wants a surgeon to simply cut out the cancers PTO, personal time off. Slide credit: clinicaloptions.com
24 Addressing Barriers to CareProvide opportunity for pt to express her feelings and concerns Reiterate information provided by the oncology team to help ensure she understands that this is breast cancer in the bones and lungs Reinforce that the current philosophy of treating her cancer as a chronic disease differs from before when the goal was curative Inform pt about resources available for financial support Optimize work, treatment schedules to save time when feasible Transportation services Discount drug programs through pharmas ADA and FMLA for work ADA, American With Disabilities Act; FMLA, Family and Medical Leave Act. Slide credit: clinicaloptions.com
25 Addressing Barriers to CareProvide written materials To explain further what metastatic breast cancer is and the basics of how it is managed To explain to her children how their mom will be treated for her metastatic breast cancer Discuss symptom management Talk with the oncologist about referral to radiation oncology for possible palliative radiation therapy to alleviate pain caused by bone metastasis Discuss consultation with palliative care team early on and present concept to pt as being for “quality of life preservation” or “quality of life restoration” to undo the myths and fears of what is meant and intended by palliative care Slide credit: clinicaloptions.com
26 Treatment Options for This Pt With Metastatic TNBCLack of a pCR with neoadjuvant chemotherapy put pt at high risk for relapse Concern for limited treatment options following progression after standard chemotherapeutic regimen Appears to be resistant to anthracycline and taxane Evaluate for clinical trial eligibility pCR, pathologic CR; TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com
27 Additional Steps by Nurse NavigatorPt was not referred in the past for genetics counseling and testing. Given pt is in her 30s with TNBC, she meets criteria for genetics referral Patient education if positive for BRCA mutation: May be a candidate for clinical trials that are targeted for BRCA-positive mutation, triple-negative pts 50% of her offspring would likely carry the same gene. This is important for their future medical healthcare Would also affect her siblings, potentially with 50% of them also being effected by the gene mutation TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com
28 Genetics Results Pt tested positive for BRCA2 gene mutation, but unfortunately no clinical trials were available; pt was prescribed gemcitabine/ carboplatin Nurse navigator provided educational information to pt and family regarding BRCA2 gene and impact of carrying the mutation One half of siblings, one half of offspring will carry the same mutation (unrelated to sex) Children too young for testing at this time Increased risk of breast, ovarian, early-stage prostate, melanoma, and pancreatic cancers for those carrying the gene mutation Nurse navigator assisted other family members (siblings and parents) to obtain genetic counseling and testing appointment Slide credit: clinicaloptions.com
29 Systemic Therapies for TNBC“No single agent has demonstrated superiority in the treatment of pts with advanced breast cancer” Use of bevacizumab controversial First-line systemic therapies Strongest evidence: taxanes and anthracyclines Other options: capecitabine, gemcitabine, platinum- based compounds, vinorelbine, and ixabepilone TNBC, triple-negative breast cancer. Slide credit: clinicaloptions.com Partridge AH, et al. J Clin Oncol. 2014;32:
30 Systemic Therapies Under Investigation for Metastatic TNBC ± BRCAAndrogen receptor inhibitors[1] PARP inhibitors[2] Can be used as single agents, with cytotoxic chemotherapy, or with ionizing radiation Examples: veliparib (ABT-888), olaparib (AZD2281) Mechanism of action: block DNA repair proteins Proposed to prevent cancer cell repair after damage from chemotherapy; may be particularly effective with BRCA mutation PARP, poly ADP ribose polymerase; TNBC, triple-negative breast cancer. 1. Rampurwala M, et al. Clin Adv Hematol Oncol. 2016;14: Boerner JL, et al. PLoS One. 2015;10:e Slide credit: clinicaloptions.com
31 Additional Immunotherapeutic Agents in Metastatic TNBCAvelumab: phase 1b JAVELIN solid tumor trial[1] ORR: 8.6% metastatic TNBC (n = 58) vs 4.2% overall (N = 168) Higher response rate in tumors with “hotspots” of PD-L1+ vs PD-L1- immune cells: 33.3% (4/12) vs 2.4% (3/124) Acceptable safety profile Atezolizumab: in combination with nab-paclitaxel in phase Ib study in solid tumors[2] ORR: 42% (n = 24) Well tolerated Phase III: pembrolizumab,[3,4] atezolizumab + nab-paclitaxel[5-7] TNBC, triple-negative breast cancer. 1. Dirix LY, et al. SABCS Abstract S Adams S, et al. SABCS Abstract P ClinicalTrials.gov. NCT ClinicalTrials.gov. NCT Pusztai L, et al. Clin Cancer Res. 2016;[Epub ahead of print]. 6. ClinicalTrials.gov. NCT ClinicalTrials.gov. NCT Slide credit: clinicaloptions.com
32 ER+ BC With Distant Recurrence After Extended Adjuvant TherapyBC, breast cancer; ER, estrogen receptor.
33 Case 2: ER+ BC With Distant Recurrence After Extended Adjuvant TherapyMs Lopez, 64-yr-old postmenopausal Hispanic female diagnosed 10 yrs earlier with stage IIA, pT2N0M0, ER/PgR+, HER2-negative right breast IDC G2 Pt treated with anastrozole for 5 yrs. Occasionally considered stopping due to persistent AI-related muscle aches and pains but took it faithfully. Declined to continue with anastrozole after initial 5 yrs of treatment Approximately 4 yrs later, pt reported new onset of low back pain radiating to left leg MRI ordered by PCP. Showed extensive abnormal decreased T2 and enhancement involving the lumbosacral spine. Replacement of the majority of L5 vertebral body. No spinal cord infringement noted. Oncology consultation recommended AI, aromatase inhibitor; BC, breast cancer; ER, estrogen receptor; IDC, invasive ductal carcinoma; PCP, primary care physician; PgR, progesterone receptor. Slide credit: clinicaloptions.com
34 Case 2: ER+ BC With Distant Recurrence After Extended Adjuvant TherapyMs Lopez’s oncologist orders the following tests PET/CT: numerous scattered intensely FDG-avid boney lesions, predominantly lytic, including multiple scattered throughout the low vertebrae, mid sternum, and multiple ribs bilaterally; 2 irregularly shaped lesions in the right middle lobe of the lung, 1.5 cm and 0.8 cm Labs: CBC, WNL; CMP, WNL except for alkaline phosphatase U/L; SGOT 51 U/L; SGPT 87 U/L; LDH 244 U/L; CA27-29: 7.96 U/mL; CEA: 13.5 ng/mL Pathology: right middle lobe lung biopsy (to confirm MBC histology & rerun breast prognostic panel): metastatic adenocarcinoma consistent with breast cancer, grade 3; ER/PgR+, HER2 (IHC) 2+/equivocal, HER2 (FISH): nonamplified; Ki-67 80% Results: diagnosed with ER+ MBC BC, breast cancer; CBC, complete blood count; CMP, complete metabolic profile; ER, estrogen receptor; PgR, progesterone receptor; MBC, metastatic breast cancer; WNL, within normal limits. CBC: WNL; CMP: WNL except for alkaline phosphatase 180 U/L (normal U/L); SGOT 51 U/L (normal U/L); SGPT 87 U/L (normal U/L). LDH 244 U/L (normal U/L). CA27-29: 7.96 U/mL (normal U/mL). CEA: 13.5 ng/mL (normal ng/mL). Slide credit: clinicaloptions.com
35 Aromatase Inhibitor–Associated Musculoskeletal SyndromeAfter the previous 5 yrs of treatment with anastrozole, Ms Lopez had declined further treatment due to muscle pain May limit adherence or AI-related survival benefit, affect QoL ≈ 50% of women on AIs report joint pain/stiffness; 20% to 30% discontinue treatment Diffused, mixed, or persistent neuropathic joint pain most common characteristic Symmetric joint pain/stiffness symptoms may be most noticeable on awakening; often improve with morning activities Risk factors not fully characterized but could include: Previous chemotherapy, hormone replacement, or taxane therapy Hormone receptor positivity Obesity AI, aromatase inhibitor; QoL, quality of life. Yang GS, et al. Cancer Nurs. 2016;[Epub ahead of print]. Park JY, et al. J Korean Surg Soc. 2013;85: Slide credit: clinicaloptions.com
36 AIMSS Interventions Early pt education is key[1]AIMSS is a common adverse event; an expectant pt may be more likely to tolerate and report the problem Inform of simple interventions that may help with arthralgia NSAIDs commonly prescribed for pain HOPE study[2]: postmenopausal women with AI-associated arthralgias (N = 121) randomized to twice-weekly supervised strength training plus home-based aerobic exercise vs usual care Pts in exercise arm demonstrated significant reductions in worst joint pain scores, pain severity, body weight along with significant increase in cardiorespiratory fitness vs usual care AI, aromatase inhibitor; AIMSS, aromatase inhibitor–associated musculoskeletal syndrome; NSAID, nonsteroidal antiinflammatory drug. 1. Nirvavath P. Ann Oncol. 2013;24: 2. Irwin ML, et al. J Clin Oncol. 2015;33: Slide credit: clinicaloptions.com
37 Barrier Assessment by Nurse NavigatorCultural: resistant to telling her family; confided that she never told her 3 sisters or mother about her original diagnosis and treatment 4 yrs ago Financial: Very dependent on her job as a bank teller to pay her bills and has little money saved for extra expenses Unmarried, no children, lives alone in a rented apartment Does not have a prescription card through her health insurance plan Has used up all of her PTO for this calendar yr PTO, personal time off. Slide credit: clinicaloptions.com
38 Addressing Barriers to CareEncourage pt to confide in her family and make them aware; offer to meet with the family with her present to explain her breast cancer history and current clinical status Advise pt to use discounted drug programs through pharmas to offset expenses associated with treatments Work with the pt and treatment team to determine if she can work during treatment, based on each line of therapy and what is involved Provide information about ADA and FMLA Link pt to advocacy organization that provides food and assistance with hormonal therapy prescriptions so that she can apply some of her monthly food money to treatment-related copayments and deductibles ADA, Americans With Disabilities Act; FMLA, Family and Medical Leave Act. Slide credit: clinicaloptions.com
39 Endocrine Therapy for Recurrent or Stage IV DiseaseRegimen Premenopausal Pts Selective ER modulators or ovarian ablation/suppression plus endocrine therapy as for postmenopausal women Postmenopausal Pts Non-steroidal AI or steroidal aromatase inactivator Tamoxifen or toremifene Exemestane + everolimus Megestrol acetate Palbociclib + letrozole Fluoxymesterone Palbociclib + fulvestrant (Category 1) Ethinyl estradiol Fulvestrant AI, aromatase inhibitor; ER, estrogen receptor. All agents are Category 2A recommendations unless otherwise indicated. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
40 Combining Targeted and Anti-estrogen Therapies in HR-Positive Breast CancerEGFR HER2 E Aromatase Inhibitor Nonsteroidal AIs: Anastrozole Letrozole Steroidal AI: Exemestane TKI E RAS PI3K PTEN ER Downregulator Fulvestrant Raf ER E mTOR Inhibitors Everolimus Sirolimus Temsirolimus Akt MEK MAPK AI, aromatase inhibitor; E, estrogen; HR, hormone receptor; MAPK, mitogen activated protein kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; PTEN, phosphatase and tensin homolog; RAS, renin-angiotensin system; TKI, tyrosine kinase inhibitor. mTOR Selective ER Modulators Tamoxifen Toremifene CDK4/6 Inhibitors Palbociclib Abemaciclib Ribociclib Cell Cycle ER E ER E ER target gene transcription HDAC Inhibitor Entinostat Transcription Silencing Slide credit: clinicaloptions.com Johnston SR. Clin Cancer Res. 2010;16:
41 Phase I Dose-Limiting ToxicitiesCDK4/6 Inhibitors in Hormone Receptor–Positive Metastatic Breast Cancer Agent Target (IC50, nM) Phase III Trials Phase I Dose-Limiting Toxicities Palbociclib (PD ) CDK4 (11) CDK6 (15) First-line combo: Letrozole* Second-line combo: Exemestane Fulvestrant* Neutropenia, thrombocytopenia‡ Abemaciclib (LY ) CDK4 (2) CDK6 (10) Anastrozole or letrozole Fulvestrant Fatigue Ribociclib (LEE011) CDK4 (10) CDK6 (39) Letrozole Tamoxifen or NSAI† Neutropenia, mucositis, pulmonary embolism, asymptomatic thrombocytopenia, hyponatremia, QTcF prolongation (> 500 ms), increased creatinine NSAI, nonsteroidal aromatase inhibitor. * Approved. †Premenopausal women; NSAI in combination with goserelin. ‡Phase II grade 3/4. Slide credit: clinicaloptions.com Hamilton E, et al. Cancer Treat Rev. 2016;45:
42 Selection of Appropriate TreatmentFor this pt with new onset of metastatic disease 10 yrs following diagnosis of ER+ disease and 5 yrs of endocrine therapy : IV zoledronic acid Pt education: dental exam with preventive dentistry intervention recommended prior to treatment; dental procedures during treatment should be avoided because of ONJ risk Evaluate for clinical trial eligibility Placed on palbociclib + letrozole ER, estrogen receptor; ONJ, osteonecrosis of the jaw. Slide credit: clinicaloptions.com
43 Supportive Therapy for Bone MetastasesTarget osteoclast activity to prevent skeletal-related events in pts with MBC Bone fractures Bone pain requiring radiation therapy Spinal cord compression Hypercalcemia 2 main options: IV bisphosphonates (eg, zoledronic acid, pamidronate) Fully human anti–RANK-L mAb: denosumab No known impact on OS with use of bisphosphonate or denosumab in pts with metastatic disease Both associated with ONJ development Known risk factors: poor baseline dental health, dental procedures during treatment, administration of chemotherapy or corticosteroids, poor oral hygiene with periodontal disease and dental abscess Dental exam with preventive dentistry intervention recommended prior to treatment Avoid dental procedures during treatment, if possible MBC, metastatic breast cancer; ONJ, osteonecrosis of the jaw. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
44 ER/PgR-Positive BC With Progression After 1 Year of Hormonal TherapyBC, breast cancer; ER, estrogen receptor; PgR, progesterone receptor.
45 Case 3: ER/PgR-Positive BC With Progression After 1 Yr of Hormonal TherapyMs Lake is a 41-yr-old premenopausal woman, diagnosed 18 mos ago with a clinical stage IIIA ER/PgR+, HER2-, left breast cancer She underwent neoadjuvant ddAC > ddT, left total mastectomy, and left ALND; final pathologic staging was stage IIB, pT2N1M0 Following adjuvant RT, she was placed on tamoxifen After being on tamoxifen for 1 yr, pt developed signs of fatigue and complained of right-sided pain ALND, axillary lymph node dissection; BC, breast cancer; ddAC, dose-dense doxorubicin/cyclophosphamide; ddT, dose-dense paclitaxel; ER, estrogen receptor; PgR, progesterone receptor; RT, radiation therapy. Slide credit: clinicaloptions.com
46 Case 3: ER/PgR-Positive BC With Progression After 1 Yr of Hormonal TherapyPET/CT scan Lesions right anterior 3rd, 4th ribs, right posterior 5th rib, lesion at L1 Liver: 2.3-cm hypoechoic mass in the left lateral lobe, cm hypoechoic mass in the right medial lobe Labs: CBC, WNL; CMP, WNL except for alkaline phosphatase 226 IU/L; SGOT 112 U/L; SGPT U/L CA U/mL Pathology: liver biopsy confirmed invasive ductal carcinoma, grade 3, ER positive, PgR positive, HER2 (IHC) 2+/ equivocal, HER2 (FISH) nonamplified, Ki % BC, breast cancer; CBC, complete blood count; CMP, complete metabolic panel; ER, estrogen receptor; PgR, progesterone receptor; WNL, within normal limits. Slide credit: clinicaloptions.com
47 Family and Occupational HistoryMs Lake is married, works full time, has a 17-yr-old son who is finishing high school Pt and her husband both very upset over cancer recurrence Her husband often travels for work Obtains her health insurance through her husband’s employment Slide credit: clinicaloptions.com
48 Barrier Assessment by Nurse NavigatorPt education: to understand biology of metastatic disease and treatment options Psychosocial support: husband will be caregiver at home but frequently travels for his employment Slide credit: clinicaloptions.com
49 Addressing Barriers to CareEducate pt and husband on MBC biology; reinforce that breast cancer cells have traveled to other organ sites, resulting in stage IV disease Remind pt that hormonal therapy does not always work effectively, but other therapeutic options may be available for consideration Discuss with pt and family how to determine when husband will be needed at home for physical and emotional support MBC, metastatic breast cancer. Slide credit: clinicaloptions.com
50 Addressing Barriers to CareTreatment now based on having a chronic illness; focus will be on preservation of quality of life while undergoing treatment Pt and her husband decide not to tell their son until after his graduation in 3 wks Pt wanted advice about how to communicate to her coworkers what was happening; wanted to know if she could still work during treatment Navigator recommended continuing to work, as it provides a sense of normalcy that is beneficial when dealing with such a life crisis Slide credit: clinicaloptions.com Everolimus [package insert].
51 Endocrine Resistance in ER-Positive Breast CancerApproximately 50% of hormone receptor–positive breast cancers develop resistance to endocrine therapy Almost all pts with advanced disease will develop acquired resistance to endocrine therapies De novo resistance occurs when endocrine treatment is ineffective from the outset in ER-positive pts Acquired resistance occurs when pts who initially respond to endocrine treatment become refractory The mechanisms of de novo and acquired resistance are likely similar but are not completely understood ER, estrogen receptor. Slide credit: clinicaloptions.com García-Becerra R, et al. Int J Mol Sci. 2013;14:
52 Treatment Ms Lake and her husband discuss options with her oncologist, including clinical trials and various regimens Chemical ovarian suppression advised to allow Ms Lake to take an aromatase inhibitor Pt and oncologist agree on zoledronic acid plus goserelin, exemestane, and everolimus Goserelin/ Zoladex: 3.6 mg q 4 weeks Leuprolide acetate: 3.75 mg q 4 weeks Slide credit: clinicaloptions.com
53 HER2+ MBC and Progression on Trastuzumab RegimenMBC, metastatic breast cancer.
54 Case 4: HER2+ MBC and Progression on Trastuzumab RegimenMs Simmons, 36-yr-old female diagnosed with ER/PgR-negative, HER2-positive breast cancer 3 yrs ago, s/p adjuvant TCH x 6, followed by every-3-wk trastuzumab to complete 12 mos 2 yrs after completing her trastuzumab, she was found to have osseous and hepatic metastases. She was placed on pertuzumab/trastuzumab/docetaxel as first-line treatment for her metastatic disease and has received 9 cycles to date Most recent scans show new bone lesions ER, estrogen receptor; MBC, metastatic breast cancer; PgR, progesterone receptor; s/p, status post; TCH, docetaxel/carboplatin/trastuzumab. Slide credit: clinicaloptions.com
55 Pt History Single concert pianist in a new relationshipHer mother had breast cancer in her 50s and died at 56 yrs of age Her father died of lung cancer in his late 50s She is an only child Concerned about risks to her career posed by peripheral neuropathy with her treatment Slide credit: clinicaloptions.com
56 Barrier Assessment by Nurse NavigatorPsychosocial support: pt concerned about telling her boyfriend about her diagnosis, as the relationship is very new; fears he will withdraw instead of remaining as a key supporter Financial: Self-employed and directly dependent on continuing to work, which includes a lot of travel No job-associated health insurance; purchased through a private healthcare plan with high deductible and copayments Depleted savings account and missed concert opportunities because of previous treatments Slide credit: clinicaloptions.com
57 Addressing Barriers to CareGive pt information about local agencies that provide food and prescription coverage support so that pt can redirect her food money to deductibles and copayments Provide educational information for single women on how and when to communicate with partner about breast cancer status Discuss with medical oncologist how pt treatments need to dovetail with her work schedule whenever possible Emphasize to pt that her BC is now a chronic illness and will eventually advance, necessitating preparation for next steps Discuss living beyond breast cancer Reinforce remaining optimistic for as long as it is realistic Link pt to advocacy organizations: MBCN, ACS, YSC ACS, American Cancer Society; BC, breast cancer; MBCN, Metastatic Breast Cancer Network; YSC, Young Survival Coalition. Slide credit: clinicaloptions.com
58 Chemotherapy Regimens for HER2+ Recurrent or Metastatic Breast CancerFirst-line Regimens Agents for Trastuzumab Exposed Pertuzumab + trastuzumab + docetaxel (Category 1—preferred) Pertuzumab + trastuzumab + paclitaxel (preferred) Other regimens Lapatinib + capecitabine Trastuzumab + capecitabine Trastuzumab + lapatinib (without cytotoxic therapy) Trastuzumab + other agents T-DM1 Trastuzumab + paclitaxel ± carboplatin Trastuzumab + docetaxel Trastuzumab + vinorelbine T-DM1, ado-trastuzumab emtansine. All agents are Category 2A recommendations unless otherwise indicated. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com
59 T-DM1 T-DM1: HER2-targeted antibody and microtubule inhibitor conjugate indicated as single agent for pts with HER2+ MBC who previously received trastuzumab and a taxane Pts either received prior therapy for metastatic disease or developed disease recurrence during or within 6 mos of adjuvant therapy Recommended dose: 3.6 mg/kg IV Day 1, cycled every 21 days until PD or unacceptable toxicity For IV infusion only: no IV push or bolus, no dextrose solution First infusion: 90 mins, observe pts during and for 90 mins after for fever, chills, other IRRs Subsequent infusions: 30 mins if prior infusions well tolerated, observe pt during and for 30 mins after infusion HERConnection: provides pt support materials IRR, infusion-related reactions; MBC, metastatic breast cancer; PD, progressive disease; T-DM1, ado-trastuzumab emtansine. Slide credit: clinicaloptions.com Ado-trastuzumab emtansine [package insert].
60 Treatment ConsiderationsPt concerned about impact of potential taxane-related peripheral neuropathy on her career as a concert pianist Clinician prescribes T-DM1 T-DM1, ado-trastuzumab emtansine. Slide credit: clinicaloptions.com
61 Supportive Care
62 Switching to Supportive Therapy OnlyRecommended when ECOG PS ≥ 3 or after failure to achieve a tumor response to 3 sequential chemotherapy regimens Failure to respond defined as absence of even a marginal response to chemotherapy Progressive disease following a response to chemotherapy is not considered a failure to respond Anatomically localized problems may benefit from local irradiation, surgery, or regional chemotherapy ECOG, Eastern Cooperative Oncology Group; PS, performance status. Slide credit: clinicaloptions.com
63 For All Pts With Advanced Disease, Approaching End of LifePts and families need tools/resources to “get affairs in order,” as simply saying it does not make it happen When possible, provide access to pro bono lawyers to help the pt and family legally and financially complete this difficult task Engage in discussions about palliative care and hospice very early on Dispel any negative images of these events, referring to them as “quality of life preservation” or “quality of life restoration” Arrange for a hospice visit to the home Slide credit: clinicaloptions.com Shockney LD. Nova Science Publishers, Inc
64 Reinforcing the Elements of a “Good Death” ExperienceKnowing she had purpose for living and that it was valued by at least 1 other person Leaving a legacy unrelated to inheritance Leaving no financial debt associated with the pt’s cancer treatment Feeling a connection to a higher spiritual power Being pain free Dying in the environment of her own choosing Giving and receiving forgiveness Feeling confident that the pt will be spoken of fondly after death Slide credit: clinicaloptions.com
65 Supporting the Pt: Fulfilling Hopes and Life Goals in Alternative WaysCards for children/grandchildren for various milestones that they will reach after their mom/grandmother has died Recordable children’s books for young children/future grandchildren Examples of creating a legacy A pt who loved doing community service work was honored with having a community service day, held annually, dedicated in her name by coworkers A pt asked her mother to create a nonprofit organization to support financial needs of pts with metastatic breast cancer A pt’s church held an annual fundraiser in her honor to support breast cancer research Slide credit: clinicaloptions.com
66 Go Online for More CCO Coverage of Breast Cancer!Capsule Summaries of all the key data from SABCS 2015 Additional CME-certified analyses with expert faculty commentary on: Developments in neoadjuvant and adjuvant therapy for EBC Treatment of MBC Key studies from major conferences on early and advanced breast cancer clinicaloptions.com/oncology
67 Supplemental Treatment Management Slides
68 Gemcitabine Dose: 1000 mg/m2 IV over 30 min on Days 1, 8; cycled every 21 days Extension of infusion beyond 60 mins causes clinically significant hypotension, severe flulike symptoms, myelosuppression, asthenia AEs in ≥ 20% of pts: nausea/ vomiting, anemia, hepatic transaminitis, neutropenia, increased alkaline phosphatase, proteinuria, fever, hematuria, rash, thrombocytopenia, dyspnea, peripheral edema Risks include: Low blood counts with potential need for blood transfusion and increased susceptibility to infections Pulmonary toxicity including respiratory failure and death Hemolytic-uremic syndrome and associated renal failure Hepatic toxicity including liver failure and death Contact healthcare provider for: S/s infection, fever, SOB, cough, wheezing, bruising, jaundice, prolonged/unexpected bleeding, changes in urine color/volume, pain/tenderness in right upper abdominal quadrant AE, adverse event; SOB, shortness of breath; S/s, signs and symptoms of. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com Gemcitabine [package insert].
69 Carboplatin Dose: AUC 2 IV on Days 1, 8; cycled every 21 daysDLT: bone marrow suppression GI toxicity: vomiting occurs in 65% of pts; nausea in 10% to 15% Additional toxicities of concern: peripheral neuropathy, nephrotoxicity, hepatic toxicity, electrolyte changes, allergic reactions, ISRs, pain, asthenia Most serious adverse events: Anemia, thrombocytopenia: report unusual bruising or bleeding, including black tarry stools or hematuria Infection Life-threatening allergic reaction Kidney and liver problems Loss of hearing or tinnitus Common, less serious adverse events: nausea, vomiting, diarrhea, anorexia, alopecia, peripheral neurotoxicity AUC, area under the concentration curve; DLT, dose-limiting toxicity; GI, gastrointestinal; ISR, injection-site reaction. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V © National Comprehensive Cancer Network, Inc All rights reserved. Accessed July 21, To view the most recent and complete version of the guideline, go online to NCCN.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc. Slide credit: clinicaloptions.com Carboplatin [package insert].
70 Palbociclib Kinase inhibitor indicated for hormone receptor+, HER2- advanced or MBC in combination with letrozole as initial endocrine based therapy in postmenopausal women or fulvestrant in women with PD following endocrine therapy Starting dose: 125 mg QD taken with food for 21 days, followed by 7 days off treatment Drug interactions with CYP3A medications Monitor for hematologic toxicities Serious AEs: neutropenia, PE AEs: dizziness, SOB, weakness, infections, fatigue, nausea, sore mouth, headache, easier bleeding/bruising, nosebleeds, diarrhea, constipation, hair loss, vomiting, rash, loss of appetite Take capsules orally with food in combination with letrozole (or fulvestrant); swallow capsules whole Avoid grapefruit and grapefruit juice during treatment Do not change dose or stop taking unless directed to do so May impair male fertility AE, adverse event; MBC, metastatic breast cancer; PD, progressive disease; PE, pulmonary embolism; SOB, shortness of breath. Potential for oral compliance issue for misunderstanding on how to take; need very straightforward pt instructions Slide credit: clinicaloptions.com Palbociclib [package insert].
71 Letrozole Aromatase inhibitor Dose: 2.5 mg QDContraindicated in premenopausal women Possible BMD decreases and TC increases; consider BMD and cholesterol monitoring Possible fatigue, dizziness, and somnolence; exercise caution when operating machinery AEs in > 20% of pts: hot flashes, arthralgia, flushing, asthenia, edema, arthralgia, headache, dizziness, hypercholesterolemia, increased sweating, bone pain, musculoskeletal Perform baseline BMD testing with annual monitoring AE, adverse event; BMD, bone mineral density; TC, total cholesterol. Educate pt on managing arthralgic pain and hot flashes Potential for oral compliance issue because of misunderstanding on how to take; need very straightforward pt instructions Slide credit: clinicaloptions.com Letrozole [package insert].
72 Exemestane Aromatase inhibitor Dose: one 25-mg tablet QD after a mealMost common AEs: In MBC: mild to moderate hot flushes, nausea, fatigue, increased sweating, increased appetite In early breast cancer (≥ 10%): hot flushes, fatigue, arthralgia, headache, insomnia, increased sweating Risk of BMD reduction with use Recommended dose increase to 50 mg with concomitant use of strong CYP3A4 inducers Serious AEs: bone loss that can increase bone fracture risk; chest pain, heart failure, stroke Common AEs: hot flashes, headache, depression, difficulty in breathing, fatigue, insomnia, feeling anxious, joint pain, increased sweating, upset stomach AE, adverse event; BMD, bone mineral density; MBC, metastatic breast cancer. Slide credit: clinicaloptions.com Exemestane [package insert].
73 Everolimus Irreversible steroidal aromatase inactivatorDose: one 25-mg tablet once daily after a meal Most common AEs in MBC were mild to moderate: hot flushes, nausea, fatigue, increased sweating, increased appetite Most common AEs in early breast cancer (> 10%): hot flushes, fatigue, arthralgia, headache, insomnia, increased sweating Reduction in bone density Concomitant use of strong CYP3A4 inducers decreases exemestane exposure Serious AEs: bone loss that can increase risk for bone fractures; chest pain, heart failure, stroke Common AEs: hot flashes, headache, depression, difficulty breathing, fatigue, insomnia, feeling anxious, joint pain, increased sweating, upset stomach AE, adverse event; MBC, metastatic breast cancer. Slide credit: clinicaloptions.com Everolimus [package insert].
74 T-DM1 Avoid concomitant use of strong CYP3A4 inhibitorsAEs in > 25% of pts: fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased transaminases, constipation, epistaxis Warnings and precautions: pulmonary toxicity, IRRs, hemorrhage, thrombocytopenia, neurotoxicity HER2 testing should be performed with FDA-approved tests in proficient labs IRR frequency: 1.4% Flushing, chills, pyrexia, dyspnea, hypotension, wheezing, bronchospasm, tachycardia Typically mild reactions secondary to extravasation within 24 hrs of infusion: erythema, tenderness, skin irritation, pain, or swelling at infusion site Specific treatment unknown Closely monitor infusion site for SC infiltration during administration AE, adverse event; IRR, infusion-related reactions; T-DM1, ado-trastuzumab emtansine. Slide credit: clinicaloptions.com Ado-trastuzumab emtansine [package insert].
75 T-DM1 Boxed warnings: Do not substitute for or with trastuzumab Monitor hepatic function, as hepatotoxicity, liver failure, and death have occurred Assess LVEF prior to initiation Educate pt on risk of embryo-fetal harm during pregnancy upon T- DM1 exposure; reinforce need for effective contraception Immediately seek medical attention for nausea, vomiting, abdominal pain (especially RUQ), jaundice, dark urine, generalized pruritus, anorexia Immediately contact a healthcare provider for new onset or worsening shortness of breath, cough, swelling of ankles/legs, palpitations, weight gain of ≥ 5 pounds in 24 hrs, dizziness or loss of consciousness Contact healthcare provider with a known or suspected pregnancy MotHER Pregnancy Registry enrollment (Genentech) During treatment and for 7 mos following last T-DM1 dose, females must use effective contraception, must not breast-feed LVEF, left ventricular ejection fraction; RUQ, right upper quadrant; T-DM1, ado-trastuzumab emtansine. Slide credit: clinicaloptions.com Ado-trastuzumab emtansine [package insert].