PHRM 542 Metastatic Breast Cancer

What is the choice of therapy for visceral metastatic disease?

Chemotherapy

What is the choice of therapy for brain metastatic disease?

Minimal response to systemic treatment

What does the initial treatment for metastatic breast cancer (mBC) depend on?

Receptor expression status (HR, HER2)

Define visceral metastases

Metastatic disease to the brain, lung, or liver that is causing quality of life symptoms

What are treatment options for triple negative mBC?

Chemotherapy

Immunotherapy

What are treatment options for HER2+ mBC?

Chemotherapy

Trastuzumab

+/- pertuzumab

Immunotherapy

What are treatment options for HR+ mBC?

Endocrine therapy

Chemotherapy

What are treatment options for triple positive mBC?

Chemotherapy

Trastuzumab +/- pertuzumab

Endocrine therapy

Immunotherapy

What are first line therapies for HR+, HER2- mBC?

Aromatase inhibitors for postmenopausal women

Fulvestrant (IM)

Ovarian suppression/ablation plus endocrine therapy for premenopausal women

What drug class has proven to increase overall survival vs AI or fulvestrant alone in HR+, HER2- mBC?

Addition of a CDK 4/6 inhibitor

What are second line therapies for HR+, HER2- mBC?

Sequential hormone therapy except in cases of rapid progression

Elecestrant (oral)

What is the MOA of fulvestrant and elacestrant?

Estrogen receptor antagonist

What are category 1 recommendations for CDK 4/6 inhibitor therapy in HR+, HER2- mBC?

1. AI + ribociclib

2. Fulvestrant + ribociclib

3. Fulvestrant + abemaciclib

Which CDK 4/6 inhibitor can be used in premenopausal women?

Ribociclib in combination with AI/tamoxifen

Which CDK 4/6 inhibitor can be used as monotherapy following disease progression?

Ademaciclib

When should palbociclib be dose adjusted?

Neutropenia

Hepatic dysfunction

Strong CYP3A4 inhibitors

When should ribociclib be dose adjusted?

Neutropenia

Hepatic dysfunction

QT prolongation (QTc > 500 msec)

Strong CYP3A4 inhibitors

When should abemaciclib be dose adjusted?

Neutropenia

Hepatic dysfunction

Diarrhea

Strong CYP3A4 inhibitors

Which CDK 4/6 inhibitor should be taken with food?

Palbociclib

Which CDK 4/6 inhibitor can cause QT prolongation?

RIbociclib = monitor with ECG!

Which CDK 4/6 inhibitor can cause diarrhea and a creatinine increase?

Abemaciclib

How should CDK 4/6 inhibitors be monitored?

CBC and CMP

ECG for ribociclib

What is the indication for elecastrant in HR+, HER2- mBC?

ESR1-mutated HR+/HER2- following progression on endocrine therapy and CDK 4/6 inhibitors

When is alpelisib in combination with fulvestrant used for mBC?

PIK3Ca mutated tumors (2nd line)

When should alpelisib therapy be held/interrupted?

Grade 3 dermatologic reactions

Grade 2/3 diarrhea

BG > 250-500 mg/dL

BG > 500 mg/dL

Grade 2/3 pancreatitis

When should alpelisib be permanently discontinued?

Grade 4 dermatologic reactions (SCARs)

Grade 4 diarrhea

If fasting BG < 160 mg/dL in 21 days following hyperglycemia

Pneumonitis

What anthracyclines are used for metastatic TNBC?

Doxorubicin

Liposomal doxorubicin

What taxane is used for metastatic TNBC?

Paclitaxel

What anti-metabolites are used for metastatic TNBC?

Capecitabine

Gemcitabine

What microtubule inhibitor is used for metastatic TNBC?

Vinorelbine

What agents are used for metastatic TNBC with germline BRCA 1/2 mutations?

Olaparib

Talazoparib

What platinum agents are used for metastatic TNBC?

Carboplatin

Cisplatin

What immunotherapy is used for metastatic TNBC?

Pembrolizumab

When should fam-trastuzumab deruxtecan be dose reduced?

Grade 4 neutropenia

Grade 4 thrombocytopenia

When should fam-trastuzumab deruxtecan be held?

Absolute LVEF decrease from 10-20%

When should fam-trastuzumab deruxtecan be permanently discontinued?

Infusion reaction (could also slow infusion rate)

Grade 2 interstitial lung disease/pneumonitis

When is sacituzumab govitecan used?

TNBC and HR+/HER2-

How should patients on sacituzumab govitecan be counseled?

Myelosuppression, severe diarrhea, edema, N/V

How should sacituzumab govitecan be monitored?

LFTs, electrolytes, CBC/diff, CMP

What patients may be at increased risk for adverse reactions from sacituzumab govitecan?

Patients who are homozygous for the UGT1A1*28 allele

When should patients with mBC consider discontinuing therapy?

When no response to 3 sequential regimens or ECOG performance status >/= 3

What are examples of complications of skeletal-related events (SREs) as a result of mBC with bone metastases?

Spinal cord compression/collapse

Radiation therapy to bone

Surgery to bone

Hypercalcemia

What are used to prevent and treat SREs in all mBC patients with bone metastases?

Bone-modifying agents (BMAs) are given in addition to chemotherapy or endocrine therapy if bone metastasis is present, expected survival is ≥ 3 months, and renal function is adequate

What are contraindications to BMA therapy?

Osteonecrosis of jaw, severely poor oral hygiene requiring dental work

All patients must be cleared by a dentist prior to initiation of therapy

What are appropriate options for breast cancer to bone?

Bisphosphonates

RANKL inhibitor

What are examples of bisphosphonates for mBC to bone?

Pamidronate 90 mg IV over 2 hours q4-12w

Zoledronic acid 4 mg IV over 15 min q4-12w

What should be monitored in patients on bisphosphonates?

Monitor CrCl because < 60 mL/min requires dose modification

Also monitor calcium and phosphorous

What RANKL inhibitor is used for patients with mBC to bone?

Denosumab 120 mg SQ q4w

What should be monitored in patients on denosumab?

Calcium and phosphorous (risk higher when CrCl < 30 mL/min)

NO dose adjustments for CrCl

When should BMAs be held?

Hold for at least 4 weeks prior/post invasive dental work

What is the Calvert formula used for?

Carboplatin dosing

What are the steps involved in the Calvert formula?

1. Solve for CrCl using Cockcroft-Gault

2. Add CrCl + 25

3. Multiply by AUC dose

Carboplatin dose (mg) = target AUC x (GFR + 25)

What is the max CrCl to be used in the Calvert formula even if the calculated CrCl is higher?

125 mL/min

What are the maximum doses of carboplatin per target AUC?

AUC = 6; max dose is 6 x 150 = 900 mg

AUC = 5; max dose is 5 x 150 = 750 mg

AUC = 4; max dose is 4 x 150 = 600 mg