Indications and Important Safety Information
Tarceva is indicated for:
- The treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen.
Limitations of use:
- Safety and efficacy of Tarceva have not been established in patients with NSCLC whose tumors have other EGFR mutations.
- Tarceva is not recommended for use in combination with platinum-based chemotherapy.
Tarceva in combination with gemcitabine is indicated for the first-line treatment of patients with locally advanced, unresectable, or metastatic pancreatic cancer.
WARNINGS AND PRECAUTIONS
- Interstitial Lung Disease (ILD):
- Cases of serious ILD, including fatal cases, can occur with
Tarceva treatment. The overall incidence of ILD in
approximately 32,000 Tarceva-treated patients in uncontrolled
studies and studies with concurrent chemotherapy was
approximately 1.1%. In patients with ILD, the onset of symptoms
was between 5 days to more than 9 months (median 39 days) after
initiating Tarceva therapy.
- Withhold Tarceva for acute onset of new or progressive
unexplained pulmonary symptoms such as dyspnea, cough, and
fever pending diagnostic evaluation. If ILD is confirmed,
permanently discontinue Tarceva.
- Renal Failure:
- Hepatorenal syndrome, severe acute renal failure including
fatal cases, and renal insufficiency can occur with Tarceva
treatment. Renal failure may arise from exacerbation of
underlying baseline hepatic impairment or severe
- The pooled incidence of severe renal impairment in the 3
monotherapy lung cancer studies was 0.5% in the Tarceva arms
and 0.8% in the control arms. The incidence of renal impairment
in the pancreatic cancer study was 1.4% in the Tarceva plus
gemcitabine arm and 0.4% in the control arm.
- Withhold Tarceva in patients developing severe renal
impairment until renal toxicity is resolved. Perform periodic
monitoring of renal function and serum electrolytes during
- Hepatotoxicity With or Without Hepatic
- Hepatic failure and hepatorenal syndrome, including fatal
cases, can occur with Tarceva treatment in patients with normal
hepatic function; the risk of hepatic toxicity is increased in
patients with baseline hepatic impairment.
- Hepatic Toxicity: One Tarceva-treated patient
experienced fatal hepatic failure and four additional
patients experienced grade 3-4 liver test
- In clinical studies where patients with moderate to severe
hepatic impairment were excluded, the pooled incidence of
hepatic failure in the 3 monotherapy lung cancer studies was
0.4% in the Tarceva arms and 0% in the control arms. The
incidence of hepatic failure in the pancreatic cancer study was
0.4% in the Tarceva plus gemcitabine arm and 0.4% in the
- Perform periodic liver testing (transaminases, bilirubin,
and alkaline phosphatase) during treatment with Tarceva.
Increased frequency of monitoring of liver function is required
for patients with pre-existing hepatic impairment or biliary
- Withhold Tarceva in patients without pre-existing hepatic impairment for total bilirubin >3 x ULN or transaminases >5 x ULN. Withhold Tarceva in patients with pre-existing hepatic impairment or biliary obstruction for doubling of bilirubin or tripling of transaminases values over baseline.
- Discontinue Tarceva in patients whose abnormal liver tests
meeting the above criteria do not improve significantly or
resolve within 3 weeks.
- Gastrointestinal Perforation:
- Gastrointestinal perforation, including fatal cases, can
occur with Tarceva treatment. Patients receiving concomitant
anti-angiogenic agents, corticosteroids, NSAIDs, or
taxane-based chemotherapy, or who have prior history of peptic
ulceration or diverticular disease may be at increased risk of
- The pooled incidence of gastrointestinal perforation in the
3 monotherapy lung cancer studies was 0.2% in the Tarceva arms
and 0.1% in the control arms. The incidence of gastrointestinal
perforation in the pancreatic cancer study was 0.4% in the
Tarceva plus gemcitabine arm and 0% in the control arm.
- Permanently discontinue Tarceva in patients who develop
- Bullous and Exfoliative Skin Disorders:
- Bullous, blistering and exfoliative skin conditions,
including cases suggestive of Stevens-Johnson syndrome/toxic
epidermal necrolysis, which in some cases were fatal, can occur
with Tarceva treatment.
- The pooled incidence of bullous and exfoliative skin
disorders in the 3 monotherapy lung cancer studies was 1.2% in
the Tarceva arms and 0% in the control arms. The incidence of
bullous and exfoliative skin disorders in the pancreatic cancer
study was 0.4% in the Tarceva plus gemcitabine arm and 0% in
the control arm.
- Discontinue Tarceva treatment if the patient develops
severe bullous, blistering or exfoliating conditions.
- Cerebrovascular Accident:
- In the pancreatic carcinoma trial, 7 patients in the Tarceva plus gemcitabine group developed cerebrovascular accidents (incidence: 2.5%). One of these was hemorrhagic and was the only fatal event. In comparison, in the placebo plus gemcitabine group there were no cerebrovascular accidents. The pooled incidence of cerebrovascular accident in the 3 monotherapy lung cancer studies was 0.6% in the Tarceva arms and not higher than that observed in the control arms.
- Microangiopathic Hemolytic Anemia With
- The pooled incidence of microangiopathic hemolytic anemia
with thrombocytopenia in the 3 monotherapy lung cancer studies
was 0% in the Tarceva arms and 0.1% in the control arms. The
incidence of microangiopathic hemolytic anemia with
thrombocytopenia in the pancreatic cancer study was 1.4% in the
Tarceva plus gemcitabine arm and 0% in the control arm.
- Ocular Disorders:
- Decreased tear production, abnormal eyelash growth,
keratoconjunctivitis sicca or keratitis can occur with Tarceva
treatment and can lead to corneal perforation or
- The pooled incidence of ocular disorders in the 3
monotherapy lung cancer studies was 17.8% in the Tarceva arms
and 4% in the control arms. The incidence of ocular disorders
in the pancreatic cancer study was 12.8% in the Tarceva plus
gemcitabine arm and 11.4% in the control arm.
- Interrupt or discontinue Tarceva therapy if patients
present with acute or worsening ocular disorders such as eye
- Hemorrhage in Patients Taking Warfarin:
- Severe and fatal hemorrhage associated with International
Normalized Ratio (INR) elevations can occur when Tarceva and
warfarin are administered concurrently.
- Regularly monitor prothrombin time and INR during Tarceva
treatment in patients taking warfarin or other
- Embryo-Fetal Toxicity:
- Based on animal data and its mechanism of action, Tarceva can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus.
- Advise females of reproductive potential to use effective contraception during therapy and for one month after the last dose of Tarceva.
MOST COMMON ADVERSE REACTIONS
- Metastatic NSCLC – First-Line Treatment of Patients
With EGFR Mutations:
- Most frequent (≥30%) adverse reactions were diarrhea,
asthenia, rash, cough, dyspnea, and decreased appetite.
- Most frequent Grade 3/4 (NCI-CTC Version 3.0) adverse reactions were rash
(14%) and diarrhea (5%). In Tarceva-treated patients, the most
frequently reported adverse reactions leading to dose
modification were rash (13%), diarrhea (10%), and asthenia
- Advanced Pancreatic Cancer - Tarceva Administered Concurrently with Gemcitabine:
- Fatigue, rash, nausea, anorexia, and diarrhea.
- Grade 3/4 (NCI-CTC version 2.0) rash and diarrhea were each reported in 5% of patients. Rash and diarrhea each resulted in dose reductions in 2% of patients and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.
You may report side effects to the FDA at (800) FDA-1088 or
www.fda.gov/medwatch. You may also report side effects to Genentech at
Please see the Tarceva full Prescribing Information for
additional Important Safety Information.