Targeted Therapy: Complete Treatment Guide
Quick Facts About Targeted Therapy
- Targets specific proteins, genes, or pathways in cancer cells
- Requires biomarker/molecular testing before starting
- Generally more precise with fewer side effects than chemotherapy
- Available as oral pills or intravenous infusions
- Resistance typically develops after 9-18 months
What is Targeted Therapy?
Targeted therapy is a type of cancer treatment that uses drugs designed to target specific proteins, genes, or molecular pathways that contribute to cancer growth and survival. Unlike chemotherapy, which affects all rapidly dividing cells, targeted therapies are designed to attack cancer cells more precisely while causing less damage to normal cells.
This approach represents the foundation of precision medicine - matching specific treatments to the unique molecular characteristics of each patient's cancer. Targeted therapy has revolutionized treatment for many cancer types, particularly lung cancer, breast cancer, melanoma, and chronic myeloid leukemia.
Key Points
- Works only if your cancer has specific molecular targets (biomarkers)
- Requires molecular/genetic testing of tumor tissue or blood
- Often combined with chemotherapy, immunotherapy, or other treatments
- Generally causes different side effects than chemotherapy
- Drug resistance is common - median response duration 9-18 months
- Next-generation drugs available when resistance develops
How Targeted Therapy Works
Targeted therapies interfere with specific molecules involved in cancer growth, progression, and spread:
Mechanisms of Action
- Signal blocking: Prevents growth signals from reaching cancer cells
- Receptor inhibition: Blocks receptors on cancer cell surface (EGFR, HER2, ALK)
- Angiogenesis inhibition: Prevents new blood vessel formation that feeds tumors (VEGF inhibitors)
- Cell cycle disruption: Stops cancer cells from dividing (CDK4/6 inhibitors)
- DNA repair blocking: Prevents cancer cells from repairing damaged DNA (PARP inhibitors)
- Protein degradation: Destroys specific proteins cancer cells need (proteasome inhibitors)
The key difference from chemotherapy: targeted therapies exploit specific vulnerabilities in cancer cells that normal cells don't have, leading to more selective cancer cell killing.
Precision Medicine Approach
Your oncologist will order molecular testing (genomic profiling, next-generation sequencing, or specific biomarker tests) to identify whether your cancer has targetable mutations or alterations. Not all cancers have targetable changes, and different cancer types have different common targets.
Types of Targeted Therapy
Small Molecule Inhibitors
Small drugs that can enter cells and interfere with specific proteins inside the cell.
- Usually taken as oral pills
- Examples: Tyrosine kinase inhibitors (TKIs)
- Daily administration at home
- Convenient but requires adherence
Monoclonal Antibodies
Large protein molecules that bind to specific targets on the cancer cell surface.
- Given intravenously (IV infusion)
- End in "-mab" (trastuzumab, bevacizumab)
- Require clinic visits
- Usually every 2-3 weeks
Antibody-Drug Conjugates
Monoclonal antibodies linked to chemotherapy drugs, delivering chemo directly to cancer cells.
- Combines targeting with cytotoxic payload
- IV administration
- T-DM1 (Kadcyla) for HER2+ breast cancer
Combination Approaches
Often combined with other treatments for synergistic effects.
- Targeted + chemotherapy
- Targeted + immunotherapy
- Dual targeted therapy
- Sequential targeted agents
Major Drug Categories
Tyrosine Kinase Inhibitors (TKIs)
The largest class of targeted therapies, blocking enzymes that promote cell growth:
- EGFR inhibitors: Erlotinib, gefitinib, osimertinib (lung cancer)
- ALK inhibitors: Crizotinib, alectinib, lorlatinib (ALK+ lung cancer)
- ROS1 inhibitors: Crizotinib, entrectinib (ROS1+ lung cancer)
- BRAF inhibitors: Vemurafenib, dabrafenib (BRAF-mutant melanoma)
- HER2 inhibitors: Lapatinib, neratinib (HER2+ breast cancer)
- VEGF inhibitors: Sunitinib, pazopanib, cabozantinib (kidney cancer)
- BCR-ABL inhibitors: Imatinib, dasatinib, nilotinib (CML)
- FLT3 inhibitors: Midostaurin, gilteritinib (FLT3+ AML)
- JAK inhibitors: Ruxolitinib (myelofibrosis)
mTOR Inhibitors
Block the mTOR protein involved in cell growth:
- Everolimus (breast cancer, kidney cancer, neuroendocrine tumors)
- Temsirolimus (kidney cancer)
CDK4/6 Inhibitors
Prevent cancer cells from dividing:
- Palbociclib (Ibrance)
- Ribociclib (Kisqali)
- Abemaciclib (Verzenio)
- Used for hormone receptor-positive breast cancer
PARP Inhibitors
Block DNA repair in cancer cells with BRCA mutations:
- Olaparib (Lynparza) - ovarian, breast, pancreatic, prostate cancer
- Rucaparib (Rubraca) - ovarian cancer
- Niraparib (Zejula) - ovarian cancer
- Talazoparib (Talzenna) - breast cancer
Proteasome Inhibitors
Prevent breakdown of proteins in cancer cells:
- Bortezomib (Velcade) - multiple myeloma
- Carfilzomib (Kyprolis) - multiple myeloma
- Ixazomib (Ninlaro) - multiple myeloma
Biomarker Testing
Before starting targeted therapy, your cancer must be tested to determine if it has the specific molecular targets. This is called biomarker testing, molecular profiling, or genomic testing.
Types of Testing
- Single gene tests: Test for one specific mutation (e.g., EGFR mutation test)
- Multi-gene panels: Test for multiple genes simultaneously
- Next-generation sequencing (NGS): Comprehensive genomic profiling of hundreds of genes
- Immunohistochemistry (IHC): Tests for protein expression (e.g., HER2, PD-L1)
- FISH testing: Fluorescence test for gene amplification or rearrangement
- Liquid biopsy: Blood test for circulating tumor DNA (ctDNA)
When Testing is Done
At Diagnosis
Comprehensive molecular testing on tumor biopsy or surgical specimen
At Progression
Repeat testing if cancer grows on targeted therapy to identify resistance mechanisms
Serial Monitoring
Liquid biopsies to monitor response and detect emerging resistance
Important Testing Notes
- Results typically take 1-3 weeks
- Not all cancers have targetable mutations (about 30-40% of lung cancers, 60-70% don't)
- Insurance usually covers testing for advanced cancers
- Request comprehensive NGS panel rather than single gene tests when possible
- Keep a copy of your molecular testing results
How Targeted Therapy is Given
Oral Medications (Pills)
Many targeted therapies are oral medications taken at home:
- Advantages: Convenient, no clinic visits for drug administration, flexibility
- Challenges: Requires adherence, managing side effects at home, cost (often expensive copays)
- Timing: Some must be taken on empty stomach, others with food - follow instructions carefully
- Storage: Most require room temperature storage away from heat/moisture
Oral Medication Adherence Tips
- Set daily alarms as reminders
- Use pill organizers
- Keep medication with you when traveling
- Never double up if you miss a dose - contact your team
- Don't stop without consulting your oncologist
- Keep medication in original bottles with labels
Intravenous (IV) Infusions
Monoclonal antibodies and some other targeted drugs are given IV:
- Frequency: Usually every 2-3 weeks
- Duration: 30 minutes to several hours
- Location: Infusion center or clinic
- Monitoring: Vital signs checked, observation for infusion reactions
Treatment Duration
- Continuous treatment: Most targeted therapies are given continuously until progression or intolerable side effects
- No defined end date: Unlike chemotherapy cycles, treatment continues as long as it's working
- Dose modifications: Doses may be reduced or temporarily held for side effects
- Treatment breaks: Some patients take scheduled breaks or intermittent dosing
Common Targeted Therapy Drugs
| Drug (Brand Name) | Target | Cancer Types | Route |
|---|---|---|---|
| Imatinib (Gleevec) | BCR-ABL | Chronic myeloid leukemia (CML), GIST | Oral |
| Erlotinib (Tarceva) | EGFR | EGFR-mutant lung cancer | Oral |
| Osimertinib (Tagrisso) | EGFR (including T790M) | EGFR-mutant lung cancer | Oral |
| Crizotinib (Xalkori) | ALK, ROS1 | ALK+ or ROS1+ lung cancer | Oral |
| Alectinib (Alecensa) | ALK | ALK+ lung cancer | Oral |
| Vemurafenib (Zelboraf) | BRAF V600E | BRAF-mutant melanoma | Oral |
| Dabrafenib (Tafinlar) | BRAF V600 | BRAF-mutant melanoma, lung cancer | Oral |
| Trastuzumab (Herceptin) | HER2 | HER2+ breast, gastric cancer | IV |
| Pertuzumab (Perjeta) | HER2 | HER2+ breast cancer | IV |
| Bevacizumab (Avastin) | VEGF | Colorectal, lung, kidney, ovarian cancer | IV |
| Palbociclib (Ibrance) | CDK4/6 | HR+ breast cancer | Oral |
| Olaparib (Lynparza) | PARP | BRCA-mutant breast, ovarian, pancreatic, prostate | Oral |
| Sunitinib (Sutent) | Multi-kinase (VEGF, PDGF) | Kidney cancer, GIST | Oral |
| Cetuximab (Erbitux) | EGFR | Colorectal, head & neck cancer (KRAS wild-type) | IV |
| Entrectinib (Rozlytrek) | NTRK, ROS1, ALK | NTRK fusion-positive solid tumors | Oral |
Note: This is not a complete list. Many other targeted therapies are available and new drugs are constantly being approved.
Side Effects Management
When to Call Your Doctor
- Severe diarrhea (more than 6 stools/day)
- Severe rash or blistering
- High blood pressure (above 150/100)
- Chest pain or difficulty breathing
- Severe abdominal pain
- Signs of liver problems (yellowing of skin/eyes, dark urine)
- Uncontrolled bleeding
- Severe headache or vision changes
Targeted therapies generally cause different side effects than chemotherapy. Side effects vary significantly depending on the specific drug and target. Most patients do NOT experience hair loss or severe nausea.
Common Side Effects by Drug Class
Diarrhea
Very CommonEspecially with EGFR inhibitors, multi-kinase inhibitors. Managed with loperamide, diet modification, hydration.
Prevention: Avoid dairy, fiber, spicy foods initially
Skin Rash
Very CommonAcne-like rash with EGFR inhibitors. Actually correlates with treatment effectiveness.
Management: Gentle cleansers, moisturizers, topical antibiotics, oral antibiotics if severe
Hypertension
CommonEspecially with VEGF inhibitors (bevacizumab, sunitinib). Requires blood pressure monitoring.
Management: Blood pressure medications, regular monitoring
Hand-Foot Syndrome
CommonRedness, pain, blistering of palms and soles with multi-kinase inhibitors.
Prevention: Moisturize hands/feet, avoid friction, cool compresses
Fatigue
CommonLess severe than chemotherapy-related fatigue but still significant for some patients.
Management: Energy conservation, light exercise, adequate sleep
Liver Toxicity
SeriousElevated liver enzymes common, requires regular blood test monitoring.
Monitoring: Liver function tests every 2-4 weeks initially
Cardiac Effects
SeriousDecreased heart function with HER2 inhibitors (trastuzumab). QT prolongation with some TKIs.
Monitoring: Baseline and periodic echocardiograms, EKGs
Bleeding Risk
SeriousIncreased with VEGF inhibitors. Avoid surgery for 4-6 weeks.
Precautions: Report any unusual bleeding, avoid blood thinners without approval
Thyroid Problems
CommonHypothyroidism with multi-kinase inhibitors (sunitinib, sorafenib).
Monitoring: Regular thyroid function tests, thyroid replacement if needed
Vision Changes
UncommonBlurred vision, floaters with some TKIs (MEK inhibitors).
Action: Report changes immediately, eye exams
Mouth Sores
CommonEspecially with mTOR inhibitors (everolimus).
Management: Gentle oral care, magic mouthwash, avoid irritants
Nausea
CommonGenerally milder than chemotherapy-induced nausea.
Management: Take with food (if allowed), anti-nausea medications
Managing Side Effects
- Don't suffer silently: Report all side effects - many are manageable with dose adjustments or supportive medications
- Dose modifications: Temporary dose reductions or treatment breaks can help manage side effects
- Supportive care: Dermatology, cardiology, gastroenterology consultations may be helpful
- Keep taking medication: Don't stop without consulting your oncologist, even if you feel fine
Drug Resistance
One of the major challenges with targeted therapy is the development of resistance - when cancer cells develop ways to evade the drug's effects.
Why Resistance Develops
- Secondary mutations: Cancer develops new mutations that bypass the drug (e.g., T790M mutation after first-generation EGFR inhibitors)
- Alternative pathways: Cancer activates different growth pathways
- Target amplification: Cancer produces more of the target protein
- Histologic transformation: Cancer changes cell type (e.g., adenocarcinoma to small cell)
Timeline
Median duration of response varies by drug and cancer type:
- EGFR inhibitors (lung): 9-18 months
- ALK inhibitors (lung): 10-34 months (varies by generation)
- Imatinib (CML): Many years with proper response
- BRAF inhibitors (melanoma): 6-12 months (longer with combination therapy)
- HER2 inhibitors (breast): Variable, often longer with combination therapy
Overcoming Resistance
Next-Generation Drugs
Newer drugs designed to overcome specific resistance mechanisms
- Osimertinib for T790M resistance
- Lorlatinib for ALK resistance mutations
- Multiple generations available for many targets
Combination Therapy
Using multiple drugs together to block resistance pathways
- BRAF + MEK inhibitors
- Targeted therapy + immunotherapy
- Dual HER2 blockade
Rebiopsy
Testing tumor tissue at progression to identify resistance mechanisms
- Tissue biopsy or liquid biopsy
- Guides next treatment selection
- May reveal new targetable alterations
Switch Strategies
Changing to different treatment approaches
- Chemotherapy
- Immunotherapy
- Clinical trials
- Different targeted agent
Importance of Repeat Testing
When cancer progresses on targeted therapy, repeat molecular testing (tissue or liquid biopsy) is crucial. This can identify the specific resistance mechanism and guide selection of the next treatment. New actionable mutations may also emerge.
Monitoring & Follow-up
Regular Monitoring Schedule
Before Starting
- Baseline imaging (CT, PET, MRI)
- Blood tests (CBC, liver/kidney function)
- EKG and echocardiogram (for certain drugs)
- Thyroid function tests
- Blood pressure baseline
During Treatment - First Month
- Blood tests every 2 weeks
- Blood pressure checks weekly (for VEGF inhibitors)
- Symptom assessment
- Side effect monitoring
Ongoing - Every 2-3 Months
- Imaging scans to assess response
- Blood tests monthly or as needed
- Clinical examination
- Cardiac monitoring (if applicable)
Response Assessment
How doctors determine if treatment is working:
- CT/PET scans: Measure tumor size, look for new lesions
- Tumor markers: Blood tests for specific cancer markers (CEA, CA 19-9, etc.)
- Liquid biopsy: Circulating tumor DNA levels
- Clinical improvement: Symptom relief, improved function
- Physical examination: Palpable masses, lymph nodes
Laboratory Monitoring
| Test | Frequency | Purpose |
|---|---|---|
| Liver function tests (AST, ALT, bilirubin) | Every 2-4 weeks initially, then monthly | Detect hepatotoxicity |
| Complete blood count (CBC) | Monthly or as needed | Monitor for cytopenias |
| Thyroid function (TSH) | Every 2-3 months | Detect hypothyroidism |
| Kidney function (creatinine) | Monthly | Monitor renal function |
| EKG | Baseline and as needed | Monitor for QT prolongation |
| Echocardiogram | Every 3-4 months (HER2 inhibitors) | Monitor heart function |
Cost Considerations
Targeted therapies are among the most expensive cancer treatments, with significant financial implications for patients.
Cost Range
- Monthly cost: $10,000 - $15,000+ without insurance
- Annual cost: $120,000 - $180,000+
- Patient copays: Can range from $0 to $10,000+ per month depending on insurance
- Specialty pharmacy: Most oral targeted therapies require specialty pharmacy
Financial Assistance Options
Manufacturer Programs
Most drug companies offer copay assistance and patient assistance programs
- Copay cards (commercial insurance)
- Free drug programs (uninsured)
- Foundation assistance
Insurance Coverage
Work with your insurance and care team
- Prior authorization required
- Appeal denials
- Request medical exception
- Consider Medicare Part D
Independent Foundations
Nonprofit organizations providing financial assistance
- Patient Advocate Foundation
- HealthWell Foundation
- Chronic Disease Fund
- Cancer organizations
Hospital Programs
Resources through your treatment center
- Financial counselors
- Social workers
- Charity care programs
- Payment plans
Important Financial Planning
- Discuss costs BEFORE starting treatment
- Understand your insurance coverage (deductible, out-of-pocket max)
- Apply for assistance programs early - don't wait until bills accumulate
- Ask about generic alternatives (available for some older drugs like imatinib)
- Consider clinical trials - drugs are provided free
- Keep detailed records of all expenses for tax purposes
Frequently Asked Questions
How is targeted therapy different from chemotherapy?
Targeted therapy attacks specific molecular targets in cancer cells, while chemotherapy affects all rapidly dividing cells. Targeted therapy generally causes fewer systemic side effects (less nausea, hair loss) but has its own unique side effects. It requires molecular testing to identify appropriate targets.
Will targeted therapy cure my cancer?
In most cases, targeted therapy controls cancer rather than curing it. Some exceptions include chronic myeloid leukemia (CML) with BCR-ABL inhibitors, where many patients achieve long-term remission. For most solid tumors, resistance eventually develops and cancer progresses, but targeted therapy can provide significant periods of disease control.
What happens if my cancer doesn't have targetable mutations?
Not all cancers have actionable targets. If comprehensive molecular testing doesn't reveal targetable alterations, other treatment options include chemotherapy, immunotherapy (if appropriate), clinical trials, or combination approaches. Your oncologist will develop an alternative treatment plan.
Why do I need to keep taking it if my cancer is responding?
Targeted therapy requires continuous treatment to maintain response. If you stop, cancer cells that aren't actively dividing (dormant cells) or resistant clones will likely start growing again. The medication keeps suppressing cancer growth. Unlike chemotherapy cycles that have a defined end, targeted therapy is typically continued indefinitely as long as it's working.
Can I take breaks from targeted therapy?
Generally, continuous treatment is recommended. However, some patients may take treatment breaks for specific reasons (major surgery, severe side effects, patient preference). Discuss with your oncologist - some drugs and situations may allow breaks, but there's risk of progression. Intermittent dosing schedules are being studied for some drugs.
What if I miss a dose?
Don't double up. Follow specific instructions for your medication - some allow taking a missed dose if it's been less than a certain number of hours, others recommend skipping and taking the next dose as scheduled. Call your oncology team for guidance. Never stop taking medication on your own.
Can I drink alcohol while on targeted therapy?
Depends on the specific drug. Many targeted therapies are metabolized by the liver, and alcohol can increase liver stress. Some drugs have specific warnings about alcohol. Discuss with your oncologist - moderate use may be acceptable for some drugs, while others require complete avoidance.
How will I know when the drug stops working?
Regular imaging scans (usually every 2-3 months) monitor tumor response. Signs of progression include growing tumors, new lesions, rising tumor markers, or worsening symptoms. When progression is detected, your oncologist will discuss repeat testing to identify resistance mechanisms and next treatment options.
Are there any drug interactions I should worry about?
Yes, many targeted therapies have significant drug interactions, especially with medications metabolized by the same liver enzymes (CYP450 system). Always inform all your doctors about your cancer treatment. Be cautious with: antibiotics, antifungals, seizure medications, heart medications, grapefruit juice, and herbal supplements (especially St. John's Wort). Check with your oncology pharmacist before starting any new medications or supplements.
Can I travel while on oral targeted therapy?
Yes, with planning. Bring extra medication, keep it in carry-on luggage in original bottles, bring a copy of your prescription, and research medical facilities at your destination. Consider travel insurance. Ensure you have enough medication plus extra in case of travel delays. Some medications require specific storage conditions.
What about side effects that develop after months of treatment?
Some side effects appear or worsen with prolonged treatment (cumulative toxicity). Examples include hypothyroidism with multi-kinase inhibitors or cardiac dysfunction with HER2 inhibitors. This is why ongoing monitoring is important. Report new symptoms even if you've been on treatment for a long time. Dose adjustments may be needed.
Is targeted therapy covered by insurance?
Most insurance plans cover targeted therapy when medically necessary and biomarker testing confirms the target. However, prior authorization is usually required, and appeals may be necessary. Out-of-pocket costs can be substantial. Work with your treatment center's financial counselors and apply for assistance programs early in treatment.
Related Resources
Medical Disclaimer: This information is educational only. Treatment decisions should be made with your oncology team based on your specific cancer type, molecular profile, and individual circumstances. Not all targeted therapies are appropriate for all cancers.