Targeted Cancer Therapies


Am Fam Physician. 2021 Feb 1;103(3):155-163.

Author disclosure: No relevant financial affiliations.

Targeted cancer therapies involve chemotherapeutic agents that attack, directly or indirectly, a specific genetic biomarker found in a given cancer. Targeted oncology includes monoclonal antibodies, small molecule inhibitors, antibody-drug conjugates, and immunotherapy. For example, the monoclonal antibodies trastuzumab and pertuzumab target human epidermal growth factor receptor 2 (HER2) and are used when treating HER2-positive breast cancer. Although targeted oncology has improved survival by years for some incurable cancers such as metastatic breast and lung cancer, as few as 8% of patients with advanced cancer qualify for targeted oncology medications, and even fewer benefit. Other limitations include serious adverse events, illustrated by a 20% to 30% rate of heart attack, stroke, or peripheral vascular events among patients taking ponatinib, which is used in treating chronic myelogenous leukemia. Immune checkpoint inhibitor therapy–related adverse effects such as hypothyroidism are common, and more severe adverse events such as colitis and pneumonitis can be fatal and require immediate intervention. Drug interactions with widely prescribed medications such as antacids and warfarin are common. Additionally, financial toxicities are a problem for patients with cancer who are using costly targeted therapies. Future directions for targeted oncology include tumor-agnostic drugs, which target a given mutation and could be used in treating cancers from multiple organ types. An overview of indications, mechanism of action, and toxicities of targeted cancer therapies is offered here.

Targeted cancer therapy involves testing various types of cancer for genetic biomarkers that can predict the response to chemotherapeutic agents that attack the biomarkers directly or indirectly.1,2 In the past decade, the U.S. Food and Drug Administration (FDA) has approved approximately 40 new targeted therapies for 12 different cancers36  (Table 1). Despite this innovation, the percentage of patients with cancer who are eligible for such therapies is small. In 2018, an estimated 8.3% of 610,000 patients with advanced or metastatic cancer were eligible for targeted therapy.7 The number of patients who benefit from these drugs is even smaller and ranges widely, depending on the tumor and drug. Targeted oncology has mainly shown benefit in the metastatic (incurable) setting, with rare success for patients treated with surgery in the local or regional setting.


Targeted Cancer Therapies

In the past decade, the U.S. Food and Drug Administration has approved approximately 40 new targeted therapies for 12 different cancers.

Patients with metastatic epidermal growth factor receptor–mutated lung cancer who are treated with osimertinib (Tagrisso) live a median of 39 months, more than double the survival of similar patients who were treated with the first epidermal growth factor receptor inhibitor, erlotinib (Tarceva), between 2007 and 2011.

In 2020, the average patient out-of-pocket cost for a course of oral cancer therapy was $5,663. According to one large analysis, 20% of patients with cancer take less medication than prescribed, 19% only partially fill oral cancer therapy prescriptions, and 24% avoid filling a prescription at all.

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Clinical recommendationEvidence ratingComments

Patients with metastatic non–small cell lung cancer should receive genomic testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations and, if positive, receive targeted therapy.14,23


Consistent evidence from RCTs showing reduced mortality

Patients with metastatic colorectal cancer should receive expanded RAS testing and be evaluated for mismatch repair deficiency.26


Consistent evidence from RCT showing reduced mortality

Patients taking ponatinib (Iclusig) should also be taking low-dose aspirin as long as no contraindications exist.28


Expert opinion and consensus guideline in the absence of clinical trials

Patients and caregivers should receive education about immunotherapies and the clinical profile of possible immune-mediated adverse effects before initiation and throughout treatment and survivorship.37


Expert opinion and consensus guideline in the absence of clinical trials

Physicians should maintain a high level of suspicion for immune therapy–related adverse effects and consider whether prompt treatment with corticosteroids is indicated.37


Expert opinion and consensus guideline in the absence of clinical trials

Patients taking small molecule inhibitors should undergo careful medication review and may require dosage modification if they are taking other medications metabolized by CYP3A enzymes.33


Expert opinion and consensus guideline in the absence of clinical trials

CYP3A = cytochrome P450, family 3A; RCT = randomized controlled trial.

A = consistent, good-quality

The Authors

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CLAIRE ELIZABETH POWERS SMITH, MD, is an assistant professor of medicine in the Hematology and Oncology department at Boston (Mass.) University Medical Center. At the time this article was written, she was a fellow in hematology and medical oncology at Oregon Health & Science University, Portland....

VINAYAK PRASAD, MD, MPH, is an associate professor in the Division of Epidemiology and Biostatistics at the University of California, San Francisco. At the time this article was written, he was a professor in the Department of Epidemiology/Biostatistics with a secondary appointment in hematology and oncology at Oregon Health & Science University.

Address correspondence to Claire Elizabeth Powers Smith, MD, Boston Medical Center, 820 Harrison Avenue, FGH 1002, Boston, MA 02118 (email: Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


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