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Metastatic/Recurrent Breast Cancer Flashcards

1
Q

METASTATIC BREAST CANCER TREATMENT

Goals of therapy

A

Goals of therapy: palliation, prolongation of life (if possible) and to maximize quality of life; cure is
not likely (< 5% at 10 years); however, in some selected patients, disease may be controlled for many
years with good QOL.

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2
Q

METASTATIC BREAST CANCER TREATMENT

Response based on type

A
  • Bone and Soft Tissue Mets: tend to have better prognosis and more likely to respond to endocrine
  • Systemic visceral metastases generally require chemotherapy due to need for rapid response
  • Brain mets: generally do not respond to chemo

HR receptor positive breast cancers tend to be more indolent and respond better to endocrine vs. HR-negative

  • ER/PR or HER2 status can change w/ treatment and progression
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3
Q

METASTATIC BREAST CANCER TREATMENT

Olaparib

Biomarker

A

BRCA1/2 mutations
(germline sequencing)

Line of therapy:
ANY

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4
Q

METASTATIC BREAST CANCER TREATMENT

Talazoparib

Biomarker

A

BRCA1/2 mutations
(germline sequencing)

Line of therapy:
ANY

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5
Q

METASTATIC BREAST CANCER TREATMENT

Larotrectinib

Biomarker

A

NTRK fusion

Subsequent (after no
other satisfactory
alternative
treatments)

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6
Q

METASTATIC BREAST CANCER TREATMENT

Entrectinib

Biomarker

A

Subsequent (after no
other satisfactory
alternative
treatments)

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7
Q

METASTATIC BREAST CANCER TREATMENT

Pembrolizumab

Biomarker

A

MSI-H/dMMR

Tumor Mutational Burden High (TMB-H) defined as ≥
10 muts/mb

TNBC - PD-L1 expression

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8
Q

METASTATIC BREAST CANCER TREATMENT

Dostarlimab-gxly

Biomarker

A

Tumor Mutational BurdenHigh (TMB-H) defined as ≥
10 muts/mb

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9
Q

METASTATIC BREAST CANCER TREATMENT

Alpelisb + fulvestrant

Biomarker

A

Breast Cancer Subtype: HR-positive/HER2-negative

PIK3CA activating mutation

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10
Q

METASTATIC BREAST CANCER TREATMENT

Pembrolizumab +
chemotherapy (albumin bound paclitaxel,
paclitaxel, or gemcitabine +
carboplatin)

Biomarker

A

Breast Cancer Subtype: TNBC

PD-L1 expression using
22C3 antibody (threshold for positivity combined positive score (CPS) ≥ 10)

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11
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

TARGETS

A

1) inhibit or eliminate production of estrogen:
- Oophorectomy or LHRH agonist (PREmenopausal)
- Aromatase Inihibitor (POSTmenopausal)

2) Block effect of estrogen at cellular level:
- Selective estrogen receptor modulators (SERMs) - PRE/POSTmenopausal
- Selective estrogen down regulators (SERDs) - POSTmenopausal

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12
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

SERMS (pre and post menopausal)

A

PRE/POSTmenopausal

  • Tamoxifen
  • Toremifene: no advantage over tamoxifen, less data

Near complete cross resistance between SERMs

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13
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

AI

A
  • anastrazole
  • letrozole
  • exemestane
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14
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

Selective Estrogen Receptor Down-regulators (SERDs)

A

Fulvestrant

  • Approved for use in HR-positive, HER2-negative advanced breast cancer in postmenopausal women w/ disease progression following endocrine tx
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15
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

LHRH agonists

A
  • Leuprolide - not approved in US for breast cancer. Use in premenopausal pts only
  • Goserelin - similar efficacy to leuprolide. Approved for advanced breast CA in US
  • Triptorelin - Phase 2 trials indicate significant response in HR-positive pts as first line tx for metastatic BRCA
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16
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

Sequencing

A

Sequential HT should be offered to patients with endocrine-responsive dx

No specific order of agents recommended

If patient responds to tx, predicts benefit to another agent

NCCN guidelines recommend chemo for patients with no clinical benefit after up to 3 sequential endocrine tx regimens

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17
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

Combination vs. Sequential Single Agents

A

Sequential hormone therapy is preferred for most women with HR-positive MBC except in cases
of immediately life-threatening disease or those with rapid visceral recurrence during adjuvant
endocrine therapy

First line treatment with fulvestrant plus a non-steroidal AI may be offered as first-line
treatment

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18
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

Premenopausal women

A

ASCO guidelines strongly recommend OAS in combination with treatment options as recommended for postmenopausal women
- tamoxifen or OAS alone (new pts)

Premenopausal women who develop metastatic disease while receiving adjuvant tamoxifen or within 12 months of treatment should be treated with OAS + AI.

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19
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

NCCN Guidelines

HER2-Negative and Postmenopausal or
Premenopausal Receiving OAS

A

Preferred Regimens: 1st line
- CDK4/6 inhibitor + AI
- CDK4/6 inhibitor + fulvestrant
- SERD (fulvestrant) +/- non steroidal AI (anastrozole, letrozole)

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20
Q

METASTATIC BREAST CANCER TREATMENT

Endocrine Therapy

NCCN Guidelines

HER2-Positive and Postmenopausal or
Premenopausal Receiving OAS

A
  • AI +/- trastuzumab
  • AI +/- lapatinib
  • AI +/- lapatinib + trastuzumab
  • Fulvestrant +/- trastuzumab
  • Tamoxifen +/- trastuzumab
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21
Q

METASTATIC BREAST CANCER TREATMENT

Chemotherapy

When to consider Chemo Tx

A

Consider first-line chemotherapy for patients with:
a. ER/PR negative tumors
b. Symptomatic, visceral sites of metastases (visceral crises)
c. Faster growing; high ki-67

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22
Q

METASTATIC BREAST CANCER TREATMENT

Chemotherapy

Combination vs. sequential single agents

A

Sequential single agents are preferred, but chemotherapy combinations may be used in select
patients with high tumor burden, rapidly progressing disease, and visceral crisis

Combination regimens are generally associated with higher response rates compared to single agent chemo

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23
Q

METASTATIC BREAST CANCER TREATMENT

Chemotherapy

Combination vs. sequential single agents

A → T vs T → A vs AT (A = doxorubicin, T = paclitaxel).

A

Response rate and TTF (time to treatment failure) were higher with AT vs single agents

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24
Q

METASTATIC BREAST CANCER TREATMENT

Chemotherapy

Combination vs. sequential single agents

Docetaxel vs docetaxel + capecitabine

A

Response rates were higher with combination

TTP higher with combination

OS higher with combination

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25
METASTATIC BREAST CANCER TREATMENT Chemotherapy Combination vs. sequential single agents Paclitaxel vs paclitaxel + gemcitabine
Response rates higher in combination OS higher in combination Increased toxicity with combo - Anemia - Neutropenia - Thrombocytopenia - Neuropathy - Fatigue
26
METASTATIC BREAST CANCER TREATMENT Chemotherapy Combination vs. sequential single agents Paclitaxel vs paclitaxel + gemcitabine
Response rates higher in combination OS higher in combination Increased toxicity with combo - Anemia - Neutropenia - Thrombocytopenia - Neuropathy - Fatigue
27
METASTATIC BREAST CANCER TREATMENT Chemotherapy Preferred Agents
- Doxorubicin/Doxil - Paclitaxel - Capecitabine - Vinorelbine - Gemcitabine - Eribulin - Cisplatin or Carboplatin - Pembrolizumab + chemo (TNBC and PD-L1) - Sacituzumab govitecan-hziy (TNBC)
28
METASTATIC BREAST CANCER TREATMENT Chemotherapy Anthracyclines
Doxorubicin vs Doxil - Median PFS and OS similar between Doxil and Doxorubicin Cross-resistance with anthracyclines - Doxorubicin pretreated patients may respond to Doxil - Conversions for calculating cumulative dose have not been established but Doxil appears to be LESS cardiotoxic
29
METASTATIC BREAST CANCER TREATMENT Chemotherapy Taxanes Paclitaxel
Weekly schedules preferred - greater efficacy - better toxicity profile - BUT less convenient Side effects differ w/ weekly - less myelopsuppression - alopecia - myalgias/athralgias - peripheral neuropathy
30
METASTATIC BREAST CANCER TREATMENT Chemotherapy Taxanes Docetaxel
Q3 week dose 60-100mg/m2 - increased response rates and TTP with higher doses - similar median survival between doses groups Side effects: - neutropenia - febrile neutropenia - infection - stomatitis - diarrhea - neurosensory HIGHER toxicity with Q3wk vs Q1wk Q1 week dose 30-35mg/m2 Incomplete cross resistance with paclitaxel
31
METASTATIC BREAST CANCER TREATMENT Chemotherapy Taxanes Albumin-bound paclitaxel (nab-paclitaxel)
Response rates significantly better with albumin-bound paclitaxel every 3 weeks compared to paclitaxel q3wk
32
METASTATIC BREAST CANCER TREATMENT Chemotherapy Taxanes Capecitabine
Approved as monotherapy for metastatic breast cancer resistant to paclitaxel and an anthracycline and in combination with docetaxel for metastatic breast cancer after failing an anthracycline-containing regimen.
33
METASTATIC BREAST CANCER TREATMENT Chemotherapy Taxanes Platinum agents (CDDP, CARBO)
Preferred to taxane therapy for patients with germline BRCA mutations
34
METASTATIC BREAST CANCER TREATMENT Chemotherapy Sacituzumab govitecan MOA
Mechanism of action: Trop-2-directed monoclonal antibody and topoisomerase inhibitor conjugate. It consists of a humanized antibody attached to a small molecule, SN-38, which is a topoisomerase I inhibitor.
35
METASTATIC BREAST CANCER TREATMENT Chemotherapy Sacituzumab govitecan Indication
Indication: unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease
36
METASTATIC BREAST CANCER TREATMENT Chemotherapy Sacituzumab govitecan Toxicities
Common – neutropenia, nausea/vomiting (considered highly emetogenic), diarrhea, constipation, fatigue, anemia, alopecia, rash, decreased appetite, abdominal pain Severe - Neutropenia (black box warning). Hold for ANC < 1500/mm3 or neutropenic fever. Consider G-CSF for secondary prophylaxis. - Diarrhea (black box warning) – administer atropine for early diarrhea of any severity. Loperamide should be promptly initiated at the onset of late diarrhea. - Anaphylactic reactions – premedicate with antipyretics, H1, and H2 blockers prior to infusion. Corticosteroids may be used for patients who had prior infusion reactions. Observation for at least 30 minutes following infusion is recommended.
37
METASTATIC BREAST CANCER TREATMENT Chemotherapy Ixabepilone FDA approved indications:
Monotherapy for metastatic locally advanced BRCA after failure of anthracycline, taxane, capecitabine In combo with capecitabine for the treatment of metastatic or locally advanced BRCA after failure of anthracycline and a taxane
38
METASTATIC BREAST CANCER TREATMENT Chemotherapy Ixabepilone Toxicities
- Neutropenia (grade 3/4 50%); - febrile neutropenia (rare); - sensory neuropathy (grade 3/4 15-20%); - fatigue; myalgias/arthralgias; - infusion-related hypersensitivity reactions (uncommon with premedications); combination has slightly more neutropenia, but similar capecitabine-related adverse events
39
METASTATIC BREAST CANCER TREATMENT Chemotherapy Eribulin FDA Approved Indications:
Metastatic BRCA who have previously received ≥ 2 chemotherapeutic regimens (prior therapies should include anthracycline and taxane)
40
METASTATIC BREAST CANCER TREATMENT Chemotherapy Eribulin Adverse Events
- neutropenia - neuropathy - anemia - alopecia - asthenia/fatigue - nausea - constipation - QT prolongation
41
METASTATIC BREAST CANCER TREATMENT Chemotherapy Vinorelbine FDA approved indications:
Not FDA approved but has demonstrated activity
42
METASTATIC BREAST CANCER TREATMENT Chemotherapy Gemcitabine FDA Approved Indications
Approved in combination with paclitaxel as first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated
43
METASTATIC BREAST CANCER TREATMENT Chemoimmunotherapy Atezolizumab + albumin-bound paclitaxel
Indication has been WITHDRAWN (voluntarily)
44
METASTATIC BREAST CANCER TREATMENT Chemoimmunotherapy Pembrolizumab + chemotherapy FDA approved indications
- Locally recurrent unresectable or metastatic TNBC who tumors express PD-L1 (CPS ≥ 10) as determined by an FDA approved test
45
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy First Line Treatment
Trastuzumab + Pertuzumab + Taxane (unless CHF or compromised LVEF)
46
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Second Line Treatment
- Ado-trastuzumab emtansine (T-DM1) - Fam-trastuzumab deruxtecan-nxki
47
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Third Line Treatment
- Tucatinib + Trastuzumab + capcitabine * preferred in patients with both systemic and CNS progression - Trastuzumab + docetaxel or vino - Trastuzumab + paclitaxel +/- carb - Capecitabine + trastuzumab or lapatinib - Trastuzumab + lapatinib - Trastuzumab + other agents - Neratinib + capecitabine - Margetuximab-cmkb + chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine)
48
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Duration of Therapy
ASCO - at least 4-6 months or until maximum response, progression or unacceptable toxicities NCCN - continue until progression or unacceptable toxicity
49
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy - ER+ and/or PR+
ASCO guidelines: - HER2 targeted plus chemotherapy (Strong recommendation) - Endocrine therapy + trastuzumab or lapatinib (in selected cases) - Endocrine therapy alone (in selected cases)
50
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy TRASTUZUMAB
Activity in HER2+ MBC as single agent or in combination with chemotherapy May be safely combined with all non-anthracycline regimens and single agents that are recommended for MBC FISH Testing: - IHC 3+ or FISH positive - significant predictor for response - ICH 0-1 or FISH negative - No indication for trastuzumab
51
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy PERTUZUMAB
Addition of pertuzumab to docetaxel and trastuzumab improved PFS, OS compared to placebo NCCN recommends combo of perjeta + trastuzumab in combo with taxane as preferred 1st line
52
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Adverse Events
- Diarrhea - Rash - mucosal inflammation - febrile neutropenia - dry skin Pertuzumab discontinued if trastuzumab is discontinued
53
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Margetuximab-cmkb MOA
HER2/neu receptor antagonist that binds to extracellular domain of HER2 and inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain, and mediates antibody-dependent cellular cytotoxicity
54
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Margetuximab-cmkb Indication
In combination with chemotherapy for the treatment of adult patients with metastatic HER2-positive breast cancer who have received ≥ 2 prior anti-HER2 regimens, at least 1 of which was for metastatic disease
55
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Margetuximab-cmkb Adverse Events
Common: - fatigue/asthenia - nausea - diarrhea - vomiting - constipation - headache - pyrexia, - infusion-related reactions (all grade: 13%) - alopecia - decreased appetite Severe: - left ventricular dysfunction (1.9% of patients) - febrile neutropenia, - neutropenia/neutrophil count decrease - infusion related-reactions (1.1%), - viral pneumonia and aspiration pneumonia
56
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Ado-trastuzumab emtansine (Kadcyla) Indications
- NCCN Guidelines for HER2-positive MBC - T-DM1 has also been evaluated as monotherapy vs. physician choice (PFS - 6.2 mo vs. 3.3 mo) - CARDIOTOXIC
57
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Fam-trastuzumab deruxtecan-nxki (Enhertu) Indications
- Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti Her2 based regimens in metastatic setting DESTINY-03: New standard of care in the second line setting following trastuzumab + taxane
58
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Tucatinib (Tukysa) MOA
Tyrosine Kinase inhibitor that inhibits HER2 and HER3 phosphorylation resulting in downstream inhibition of MAPK and AKT signaling and cell proliferation
59
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Tucatinib Indications
Indications: In combination w/ trastuzumab and capecitabine for the treatment of adult patients w/ advanced unresectable or metastatic HER2+ breast cancer who have received >1 anti-HER2 based regimens
60
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Tucatinib Toxicities
Common: - diarrhea - hand foot - N/V - fatigue - anemia - stomatitis SEVERE: - diarrhea - Hepatotoxicity
61
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Neratinib + capecitabine Indications
Received >=2 prior HER2-directed regimens for metastatic disease
62
METASTATIC BREAST CANCER TREATMENT HER2 Targeted Therapy Lapatinib (Tykerb)
Efficacy: - Single agent w/ modest RR =24% for first line treatment and 8% for trastuzumab pretreated patients - Longer PFS that received letrozole + lapatinib compared to letrozole - Longer PFS in HER2+ patients that received trastuzumab + lapatinib compared to lapatinib alone - Did not improve PFS or OS when added to fulvestrant in patients w/ ER+ MBC and increased toxicity
63
METASTATIC BREAST CANCER TREATMENT CDK 4/6 Inhibitors Drugs
- Palbociclib - Ribociclib - Abemaciclib FDA: RARE Interstitial Lung Disease
64
METASTATIC BREAST CANCER TREATMENT CDK 4/6 Inhibitors Primary Use
Primary use in patients with HR+, HER2- advanced or metastatic breast cancer
65
METASTATIC BREAST CANCER TREATMENT CDK 4/6 Inhibitors PALBOCICLIB Toxicity
CDK 4/6 Inhibitor HR+, HER2- advanced - Neutropenia - Anemia - Fatigue FDA: RARE Interstitial Lung Disease
66
METASTATIC BREAST CANCER TREATMENT CDK 4/6 Inhibitors Ribociclib Toxicity
CDK 4/6 Inhibitor HR+, HER2- advanced - Neutropenia - LFT abnormality FDA: RARE Interstitial Lung Disease
67
METASTATIC BREAST CANCER TREATMENT CDK 4/6 Inhibitors Abemaciclib Toxicity
CDK 4/6 Inhibitor HR+, HER2- advanced - Diarrhea - Neutropenia - Nausea - Fatigue FDA: RARE Interstitial Lung Disease
68
METASTATIC BREAST CANCER TREATMENT Everolimus
FDA Approved for combination with exemestane - ER+ - HER2- MBC - after failure of nonsteroidal AI - Stomatitis - Rash - Diarrhea - Hyperglycemia
69
METASTATIC BREAST CANCER TREATMENT PARP Inhibitors
- olaparib - talazoparib Recurrent or Metastatic Breast Cancer for pts with germline BRCA1/2 Mutation - Usually HER2-neg but can be used in ANY subtype
70
METASTATIC BREAST CANCER TREATMENT Alpelisib
PIK3CA mutations - HR+ - HER2-neg Adverse Rxns - hyperglycemia - rash

BCOP - Breast (6 decks)

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