Erlotinib (Tarceva): Uses, Benefits, Side Effects, and What Patients Should Know

Erlotinib, also known as Tarceva, is an oral targeted cancer drug (EGFR tyrosine kinase inhibitor [TKI]) used to treat locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have activating EGFR mutations (e.g., EGFR exon 19 deletions or exon 21 [L858R] substitutions). In current practice, newer EGFR inhibitors (such as third-generation EGFR TKIs) are often preferred first-line for common EGFR mutations, and erlotinib may be used in select situations based on prior therapy, tolerability, access, and clinical factors.

Erlotinib is also indicated for pancreatic cancer in combination with gemcitabine for certain patients with locally advanced, unresectable, or metastatic disease. 

Off-label, Erlotinib has been used in select settings (e.g., some advanced kidney cancers), depending on provider judgment and evidence.

Patient Selection and Genetic Testing (EGFR)

Erlotinib is most effective in NSCLC when the tumor has an activating EGFR mutation. For this reason, EGFR mutation testing is typically performed before starting therapy. Testing may be done on a tumor tissue sample (biopsy) or, in some cases, with a blood test (“liquid biopsy”) that looks for tumor DNA in the bloodstream. If testing does not identify an activating EGFR mutation, erlotinib is generally less effective, and other treatment approaches are often preferred.

Over time, some cancers may develop resistance to EGFR inhibitors. If the cancer stops responding or progresses, your oncology team may recommend repeat testing to help guide next-step treatment choices.

Mechanism of Action

Erlotinib is a tyrosine kinase inhibitor (TKI), a type of cancer growth blocker. Its mechanism of action is to block proteins on cancer cells that encourage them to grow. These proteins are called epidermal growth factor receptors (EGFR). Erlotinib’s greatest benefit in NSCLC is seen in patients whose tumors have activating EGFR mutations; use in patients without these mutations is generally less effective and is not the preferred approach when mutation status is known. 

Is Erlotinib Chemotherapy?

According to Mayo Clinic, chemotherapy is defined as “a drug treatment that uses powerful chemicals to kill fast-growing cells in your body”, which unfortunately can include healthy non-cancerous cells. Erlotinib, therefore, is not chemotherapy. Unlike traditional cytotoxic chemotherapy, erlotinib targets the EGFR signaling pathway and is considered a targeted drug therapy.

How Erlotinib Is Taken

This medication is taken orally once daily and should be taken on an empty stomach, at least 1 hour before or 2 hours after food. It is also preferable to take the medication at the same time every day. If a patient misses a dose, they should take it as soon as they remember. If it is close to the next dose, the missed dose should be skipped, and the patient should continue with the next dose at the scheduled time. Do not take two doses at once or extra doses. 

Monitoring During Erlotinib Therapy

Your healthcare team may monitor you during treatment to help manage side effects and confirm the medication is working. Monitoring commonly includes:

• Skin and GI symptoms: Rash, dryness, diarrhea, appetite changes, and hydration status.
• Liver and renal function tests: Periodic blood work may be done because erlotinib can affect liver enzymes and kidney function, especially if a patient is dehydrated.
• Breathing symptoms: Report new or worsening cough, shortness of breath, or fever promptly.
• Eye symptoms: Report eye pain, redness, light sensitivity, or vision changes.

Dose holds, dose reductions, or supportive medications may be recommended based on your symptoms and lab results.

Dosage

Erlotinib comes in three strengths: 25 mg, 100 mg, and 150 mg tablets.

The recommended dose for NSCLC is 150 mg/day. The recommended dose for pancreatic cancer is 100 mg/day in combination with gemcitabine.

Dose reductions may be required based on tolerability, drug interactions, and clinician guidance.

Erlotinib Side Effects

The most common side effects in maintenance treatment are:

• Rash-like events
• Diarrhea

The most common side effects when this medication is used in 2nd line NSCLC are:

• Rash
• Diarrhea
• Anorexia
• Fatigue
• Dyspnea
• Cough
• Nausea
• Infection
• Vomiting

The most common side effects when this medication is used in pancreatic cancer are:

• Fatigue
• Rash
• Nausea
• Anorexia
• Diarrhea
• Abdominal pain
• Vomiting
• Weight loss
• Infection
• Edema
• Fever
• Constipation
• Bone pain
• Shortness of breath
• Mouth sores
• Muscle pain

Serious Warnings and Precautions

While many side effects are manageable, some reactions can be serious and require urgent medical evaluation:

• Interstitial lung disease (ILD)/pneumonitis (rare): Seek urgent care for sudden or worsening shortness of breath, new or worsening cough, chest discomfort, or fever.
• Liver problems (hepatotoxicity): Contact your provider if you develop yellowing of the skin/eyes (jaundice), dark urine, severe fatigue, or right-sided upper abdominal pain.
• Kidney problems: If urine becomes dark, output is low, and accompanied by weakness/fatigue, loss of appetite, and/or swelling of the ankles/feet, inform your provider immediately. 
• Severe skin reactions: If rash becomes widespread, blistering, painful, or accompanied by fever, contact your provider immediately.
• Serious GI events (rare): Severe abdominal pain, black/tarry stools, vomiting blood, or severe persistent diarrhea should be evaluated right away.
• Eye problems (keratitis/corneal irritation): Eye pain, redness, tearing, light sensitivity, or vision changes should be reported promptly.

If any severe symptoms occur, your healthcare team may advise stopping erlotinib temporarily or permanently and initiating appropriate treatment.

Drug Interactions 

Some medications can change erlotinib levels or reduce how well it is absorbed. Your prescriber may recommend avoiding certain drugs, separating doses, monitoring more closely, or adjusting the Tarceva dose as needed. The following may require avoidance, timing separation, closer monitoring, or dose adjustment: 

• Atazanavir
• Clarithromycin
• Indinavir
• Itraconazole
• Ketoconazole
• Nefazodone
• Nelfinavir
• Ritonavir
• Saquinavir
• Telithromycin
• Troleandomycin (TAO)
• Voriconazole
• Grapefruit or grapefruit juice. 

Cigarette smoking can reduce erlotinib levels. Patients should therefore stop smoking while taking this medication. However, if they continue to smoke, a cautious increase in dose may be considered. 

Drugs that alter the pH of the upper GI tract may alter the solubility of erlotinib and reduce its effects. Coadministration of erlotinib with omeprazole (a proton pump inhibitor) can decrease erlotinib’s concentration so this combination should be avoided if possible. If patients need to be treated with a H2-receptor antagonist (i.e., ranitidine), erlotinib must be taken once a day, 10 hours after the H2-receptor antagonist dosing, and at least 2 hours before the next dose of the H2-receptor antagonist. Although the effect of antacids on erlotinib has not been evaluated, the antacid and erlotinib use should be separated by several hours, if an antacid is necessary.

Erlotinib Use in Pregnancy

This medication can cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid pregnancy while on erlotinib. Adequate contraceptive methods should be used during therapy and for at least 2 weeks after completing therapy. 

Pricing

Out-of-pocket cost for erlotinib can vary widely based on strength, quantity, pharmacy/specialty channel, insurance coverage, and manufacturer or third-party assistance programs. Patients can contact their care team, insurance company, or specialty pharmacy to explore copay or financial assistance options. Contact AmeriPharma® to explore copay assistance programs.