Keeping Up With All the ’Nibs and ’Mabs

It’s difficult to keep up these days with all of the recent immunotherapy and targeted therapy drug approvals and their corresponding indications. Advanced practice nurses and oncology nurses can benefit from having a better understanding of what these therapies are, how they work, and who should be receiving them, explained Rowena Schwartz, PharmD, BCOP, in a presentation at the Oncology Nursing Society (ONS) 41^st Annual Congress, held April 28–May 1 in San Antonio, Texas.

Dr. Schwartz highlighted a few popular targets for targeted therapies along with drugs that can activate an antitumor response via the immune system:

• Phosphatidylinositol 3-kinase (PI3K): Target for B-cell lymphoproliferative disorders (chronic lymphocytic leukemia, follicular B-cell lymphoma, and small lymphocytic lymphoma).

• Bruton tyrosine kinase (BTK): Key component of B-cell receptor signaling and seen in various B-cell malignancies (chronic lymphocytic leukemia, mantle cell lymphoma).

• Cyclin-dependent kinase (CDK): Critical regulatory enzymes that drive cell cycle transitions. Deregulation of select CDK pathways is associated with some malignancies.

• Epidermal growth factor receptor (EGFR): EGFR is a cell surface protein that binds to epidermal growth factor. Mutations in the EGFR gene are typically associated with lung cancer.

• Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4): Found on the surface of T cells, CTLA-4 is a protein receptor that functions as an immune checkpoint.

• Programmed death 1/programmed death ligand 1 (PD-1/PD-L1): Activates programmed T cell death. 

The US Food and Drug Administration (FDA) approved many targeted and immunotherapy agents in 2015. Dr. Schwartz mainly focused her session on multiple myeloma, melanoma, and lung cancer.

Elotuzumab (Empliciti):

• IgG1 immunostimulatory monoclonal antibody that targets signaling lymphocytic activation molecule (SLAM7).

• Elotuzumab is approved for multiple myeloma in combination with lenalidomide and dexamethasone for those who have received one to three prior regimens.

• This drug is administered via intravenous (IV) infusion over 60 minutes. Infusion reactions have occurred in 10% of patients and often seen with the first dose. The majority of the reactions are grade 1/2.

Ixazomib (Ninlaro):

• A proteasome inhibitor, ixazomib is in the same class of drugs as bortezomib (Velcade). It is considered a second-generation proteasome inhibitor because it has improved characteristics over bortezomib.

• Ixazomib is indicated in combination with lenalidomide and dexamethasone for multiple myeloma patients who have received at least one prior therapy.

• This drug is administered as an oral 4 mg dose on days 1, 8, and 15 of each 28-day cycle. The most common side effects are gastrointestinal effects, thrombocytopenia, peripheral neuropathy, and edema.

Daratumumab (Darzalex):

• Targets CD38, a transmembrane glycoprotein expressed on the surface of myeloma cells.

• Approved as a single agent for myeloma patients that have received more than three prior therapies including a proteasome inhibitor and immunomodulatory agent.

• Daratumumab is administered via IV at a 16 mg/kg dose with varied frequency depending on the week. Most infusion reactions are associated with the first dose. Gastrointestinal effects along with pancytopenia can occur as well.

While multiple myeloma drug approvals made their mark in 2015, melanoma had a couple approvals of their own:

Cobimetinib (Cotellic):

• Blocks the activity of an enzyme known as mitogen-activated protein kinase 1 (MEK1).

• Cobimetinib is approved in combination with vemurafenib (Zelboraf) for unresectable or metastatic melanoma for patients harboring a BRAF V600E or V600K mutation.

• This drug is taken at a 60 mg dose daily for 21 days every 28 days. It is important to note that cobimetinib can interact with CYP3A4 inhibitors.

• The most common side effects are gastrointestinal, photosensitivity, and laboratory abnormalities.

Talimogene laherparepvec (Imlygic):

• Commonly referred to as TVEC, this is a genetically modified oncolytic viral therapy consisting of an engineered herpes simplex virus type 1. These oncolytic viruses recognize, infect, and destroy malignant cells with minimal effects on normal cells.

• TVEC is the first FDA-approved oncolytic virus therapy for the treatment of melanoma lesions in the skin and lymph nodes.

• TVEC consists of a series of injections into the melanoma lesions. After the initial injection, a second dose is administered 3 weeks later, followed by additional doses every 2 weeks for at least 6 months.

• One of the main side effects related to this treatment is fatigue. Immune-mediated events, injection site complications, and herpetic infections should also be assessed for patients receiving this kind of treatment.

Lastly, Dr. Schwartz discussed targeting EGFR in non–small-cell lung cancer (NSCLC). Two of the drug approvals she noted in her session were osimertinib and necitumumab:

Osimertinib (Tagrisso):

• Binds irreversibly to the EGFR kinase. Developed to have activity against tumors bearing EGFR mutations and T790M resistance mutations.

• Osimertinib is approved for patients with metastatic EGFR T790M mutation–positive NSCLC after progression on an EGFR tyrosine kinase inhibitor.

• Once the tumor specimen is confirmed to have the T790M mutation, patients take an 80 mg oral dose daily. This drug can also interact with CYP3A4 inhibitors.

• The most common side effects noted with osimertinib are diarrhea, rash, dry skin, and nail toxicity.

Necitumumab (Portrazza):

• This is a recombinant human IgG1 monoclonal antibody that blocks the activity of EGFR.

• Approved in combination with cisplatin and gemcitabine (Gemzar) for first-line treatment of patients with squamous NSCLC.

• Necitumumab is administered as an IV infusion over 60 minutes on days 1 and 8 within a 3-week cycle.

• The most common side effects of necitumumab are skin rash and magnesium deficiency.

While learning about various targets and recent drug approvals are important, understanding other issues associated with these kinds of treatments are noteworthy as well:

• Always address quality-of-life issues with the patient: side effects, financial distress, etc.

• Ongoing patient education is essential to help mitigate toxicity during and after treatment-many treatment-related side effects are delayed.

• Pay attention to grade 1/2 toxicities-most common doesn’t mean less severe.

• Always assess for unique toxicities and not just the most common-stay current with the most recent research literature.

• Be cautious when using steroids during treatment-this may make the cancer treatment less effective.