Immunotherapy Treatment for Advanced Breast Cancer

Advanced or metastatic breast cancer (mBC) can be divided into three different subtypes: estrogen-receptor (ER) positive, HER-2 positive, and triple-negative BC (TNBC). ER-positive/HER-2 negative BC accounts for about 70% of BC cases are often treated with endocrine therapy like tamoxifen and aromatase inhibitors. HER-2 positive cancers account for about 15–20% of the cases (3) and are classically treated anti-HER-2 agents such as trastuzumab. Triple negative breast cancer (TNBC) accounts for about up to 15% of cases with chemotherapy being the cornerstone of its treatment until recently.

Immuno-oncology (or immunotherapy) and precision medicine are the newest developments in the treatment of advanced cancer.  Immuno-oncology helps to restore the body’s immune system and improves outcomes when administered alone or in combination with chemotherapy.

There are several immuno-oncology treatments that work in advanced breast cancer.  Some immunotherapy drugs, like monoclonal antibodies, work in more than one way to control cancer cells and may also be considered precision medicine or targeted therapy because they block a specific protein on the cancer cell to keep it from growing.

Immune checkpoint inhibitors for breast cancer

An important part of the immune system is its ability to keep itself from attacking normal cells in the body. To do this, it uses proteins (or “checkpoints”) on immune cells that need to be turned on (or off) to start an immune response. Breast cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Drugs that target these checkpoint proteins help restore the immune response against breast cancer cells.

PD-1 inhibitor

Pembrolizumab (Keytruda) is a drug that targets PD-1 (a protein on immune system T cells that normally helps keep them from attacking other cells in the body). By blocking PD-1, these drugs boost the immune response against breast cancer cells. This can often shrink tumors.

  • Keytruda can used for breast cancer that has come back (recurred) locally but can’t be removed by surgery.  
  • Keytruda can be used for breast cancer that has spread to other parts of the body.

This drug is given as an intravenous (IV) infusion, typically every 3 or 6 weeks. In certain situations, your doctor might test your cancer cells for the PD-L1 protein to show that the cancer is more likely to respond to treatment with pembrolizumab. 

The goal of immunotherapy is to help the immune system recognize and eliminate cancer cells by either activating the immune system directly or by inhibiting mechanisms of suppression of the cancer.

TROP-2 Expression

TROP-2 expression is higher in HER2-negative breast tumors (HR+/HR. Sacituzumab govitecan (SG) is a first-in-class TROP-2-directed ADC with an anti-TROP-2 antibody conjugated to SN-38, a topoisomerase inhibitor via a hydrolysable linker.

Below is a list of mBC targets and treatment options:

Medications

Biomarker or Target

Breast Cancer Type

How to Take

Common Side Effects

Lynparza (generic name is olaparib)

BRCA1 mutation, BRCA2 mutation

Any breast cancer type with the BRCA1/2 mutations

Taken by mouth twice daily as a tablet or capsule

Skin rash
Tummy issues: nausea, vomiting, diarrhea, bloating, constipation, stomach ache, appetite loss

Talzenna (generic name is talazoparib)

BRCA1 mutation, BRCA2 mutation

Any breast cancer type with the BRCA1/2 mutations

Taken by mouth as a tablet once daily

Tiredness or weakness, hair loss
Tummy issues: nausea, vomiting, diarrhea, stomach ache, appetite loss

Perjeta (generic name

Is pertuzumab)

EGFR

HER2-

HER2+,HR+

Infusion in your vein

Extreme tiredness, dizziness, or weakness. It may also cause a headache, nausea, vomiting, diarrhea, or a decrease in appetite.

Herceptin (generic name is trastuzumab)

EGFR

HER2+

HER2+,HR+

Infusion in your vein

Overall tired or weak. It may cause a headache, chills, or pain in your bones, muscle, or joints. It may also cause tummy issues like nausea, vomiting, or diarrhea.

Phesgo (combination of pertuzumab, trastuzumab, hyaluronidase-zzxf)

 

HER2-

HER2+,HR+

This medication is a combination of Perjeta + Herceptin that can be given as an injection under the skin.

Phesgo can cause hair loss, skin rashes, or dry mouth. This can also cause diarrhea, constipation, loss of appetite, nausea, and vomiting.

Tukysa (generic name is tucatinib)

 

HER2-

HER2+,HR+

This medication is given as a tablet by mouth twice a day. It can be taken with or without food, but the tablet should be swallowed whole.

A few side effects that have been reported are general loss of strength and energy, mouth sores, tummy issues, loss of appetite, headache, and joint pain.

Kadcyla (generic name is ado-trastuzumab emtansine or T-DM1)

 

HER2-targeted therapy with a mini chemotherapy molecule (emtansine) attached to it

Kadcyla is given as an infusion into the vein over a certain period of time.

This medication can cause general tiredness, headache, dry mouth, or mouth sores. It can also cause joint or muscle pain, nerve pain, or tummy issues like nausea, constipation, diarrhea, and vomiting.

Enhertu (generic name is fam-trastuzumab deruxtecan-nxki)

 

This medication is a HER2-targeted therapy that has a mini chemotherapy molecule (deruxtecan) attached to it.

Enhertu is given as an infusion into the vein over a period of time.

It may cause you to feel overall tiredness and weakness. You may get a headache, experience hair loss, or have tummy issues like nausea, vomiting, constipation, or diarrhea. It could also decrease your appetite, or cause nosebleeds or mouth sores.

Tykerb (generic name is lapatinib)

EGFR

Antineoplasic-Epidermal.Growth Factor-EGFR (ErbB1), HER-2 (ErbB2)R.Inhibitor

This is a tablet taken by mouth once a day, at the same time each day. This should be taken on an empty stomach 1 hour before a meal, or 1 hour after a meal. Tykerb should not be taken with grapefruit.

This medication may cause headaches, skin rashes, tiredness, mouth sores, and tummy issues like nausea, vomiting, diarrhea, or bloating.

Nerlynx (generic name is neratinib)

EGFR

HER2-

This is taken as a tablet by mouth once daily. Grapefruit should be avoided while using this medication.

The most common side effect of Nerlynx is diarrhea, so you may be given a medication with Nerlynx to prevent diarrhea. Other side effects are skin rashes, tiredness, mouth sores, tummy pain, nausea, or vomiting.

Verzenio (generic name is abemaciclib)

CDK4/6 Blockers

HER2-,HR-

Triple negative

This is a tablet taken by mouth twice a day, at the same time each day. The tablet should be swallowed whole, and not crushed or chewed. Grapefruit should be avoided when using this medication.

Common side effects are tummy issues such as diarrhea, nausea, decreased appetite, stomachache, vomiting, and constipation. Other side effects are weight loss, hair loss, general weakness or tiredness, headache, and dizziness.

Ibrance (generic name is palbociclib)

CDK4/6 Blockers

HER2-,HR-

Triple negative

This is a tablet or capsule taken by mouth once a day, at the same time each day. Ibrance should be swallowed whole, and not crushed or chewed. Grapefruit should not be consumed while on this medication. 

The tablets can be taken with or without food. The capsules should be taken with food.

Common side effects are nausea, diarrhea, vomiting, and loss in appetite. It may also cause hair loss, skin rashes, or general tiredness or weakness.

Kisqali (generic name is ribociclib)

CDK4/6 Blockers

HER2-,HR-

Triple negative

This is a tablet taken by mouth once a day, at the same time each day. It is best taken in the morning. The tablets should be swallowed whole, not crushed or chewed. It can be taken with or without food, however, grapefruit should be avoided when taking Kisqali.

Common side effects are tummy issues such as nausea, diarrhea, vomiting, constipation, stomachache, and loss in appetite. It may also cause headache, general weakness, dizziness, hair loss, skin rashes, and itching.

Trodelvy (generic name is sacituzumab govitecan-hziy)

TROP2

Triple negative

This is an infusion given by vein. 

Common side effects are overall tiredness and weakness. Trodelvy can also cause tummy issues like stomach ache, constipation, loss in appetite, diarrhea, nausea, and vomiting. Other side effects are hair loss, dry skin, skin rashes, and itching.

Piqray (generic name is alpelisib)

PIK3CA mutation

HR(+), HER2(-) subtypes with the PIK3CA mutations

Taken by mouth as a tablet once daily

Used in combination with another drug called Faslodex, which is given as an injection

Tiredness, headache, hair loss, skin rash
Tummy issues: nausea, diarrhea, vomiting, stomach ache, appetite loss

Tecentriq (generic name is atezolizumab)

PD-L1 expression

HR(-), HER2(-) breast cancer that expresses PD-L1

*HR(-) with HER2(-) is also called triple negative breast cancer

Given as an infusion into the vein on certain days

Used in combination with another drug called Abraxane, which is given as an infusion into the vein

Skin rash
Tummy issues: diarrhea, vomiting, constipation, stomach ache, appetite loss

Vitrakvi (generic name is larotrectinib)

NTRK fusion

Any breast cancer type with the NTRK gene fusion

Taken by mouth as a tablet twice a day

Tiredness, dizziness, headache
Tummy issues: nausea, vomiting, constipation, diarrhea, stomach ache, appetite loss

Rozlytrek (generic name is entrectinib)

NTRK fusion

Any breast cancer type with the NTRK gene fusion

Taken by mouth as a tablet once daily

Tiredness, dizziness, headache, weight gain
Tummy issues: constipation, nausea, diarrhea, vomiting, stomach ache, taste changes, loss of appetite

Keytruda (generic name is pembrolizumab)

MSI-H or dMMR

Any breast cancer type with MSI-H or dMMR

Given as an infusion into the vein on certain days

Skin rashes, itching, tiredness, muscle or bone pain
Tummy issues: constipation, nausea, vomiting, stomach ache, diarrhea, appetite loss