Genentech BioOncology

Avastin (bevacizumab)

Metastatic Colorectal Cancer (mCRC)

Avastin is indicated for the first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum in combination with intravenous 5-fluorouracil–based chemotherapy.

Non-Squamous Non–Small Cell Lung Cancer (NSCLC)

Avastin is indicated for the first-line treatment of unresectable, locally advanced, recurrent or metastatic non–squamous non–small cell lung cancer in combination with carboplatin and paclitaxel.

Metastatic Renal Cell Carcinoma (mRCC)

Avastin is indicated for the treatment of metastatic renal cell carcinoma in combination with interferon alfa.

Boxed WARNINGS and additional important safety information

• Gastrointestinal (GI) perforation: Serious and sometimes fatal gastrointestinal perforation occurs at a higher incidence in Avastin-treated patients compared to controls. The incidences of GI perforation ranged from 0.3% to 2.4% across clinical studies. Discontinue Avastin in patients with GI perforation

• Surgery and wound healing complications: The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients. Do not initiate Avastin for at least 28 days after surgery and until the surgical wound is fully healed. The appropriate interval between termination of Avastin and subsequent elective surgery required to reduce the risks of impaired wound healing/wound dehiscence has not been determined. Discontinue Avastin at least 28 days prior to elective surgery and in patients with wound dehiscence requiring medical intervention

• Hemorrhage: Severe or fatal hemorrhage, including hemoptysis, GI bleeding, hematemesis, central nervous system hemorrhage, epistaxis, and vaginal bleeding, occurred up to 5-fold more frequently in patients receiving Avastin. Across indications, the incidence of grade ≥3 hemorrhagic events among patients receiving Avastin ranged from 1.2% to 4.6%. Do not administer Avastin to patients with serious hemorrhage or recent hemoptysis (≥1/2 tsp of red blood). Discontinue Avastin in patients with serious hemorrhage (ie, requiring medical intervention)

• Additional serious and sometimes fatal adverse events for which the incidence was increased in the Avastin-treated arm vs control included non-GI fistula formation (≤0.3%), arterial thromboembolic events (grade ≥3, 2.4%), and proteinuria including nephrotic syndrome (<1%). Additional serious adverse events for which the incidence was increased in the Avastin-treated arm vs control included hypertension (grade 3–4, 5%–18%) and reversible posterior leukoencephalopathy syndrome (RPLS) (<0.1%). Infusion reactions with the first dose of Avastin were uncommon (<3%), and severe reactions occurred in 0.2% of patients

• The most common adverse reactions observed in Avastin patients at a rate >10% and at least twice the control arm rate were epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis. Across all studies, Avastin was discontinued in 8.4% to 21% of patients because of adverse reactions

• The most common grade 3–4 events in Study 2107, which occurred at a ≥2% higher incidence in the Avastin plus IFL vs IFL groups, were asthenia (10% vs 7%), abdominal pain (8% vs 5%), pain (8% vs 5%), hypertension (12% vs 2%), deep vein thrombosis (9% vs 5%), intra-abdominal thrombosis (3% vs 1%), syncope (3% vs 1%), diarrhea (34% vs 25%), constipation (4% vs 2%), leukopenia (37% vs 31%), and neutropenia (21% vs 14%)

• The most common grade 3–5 (nonhematologic) and 4–5 (hematologic) events in Study E3200, which occurred at a higher incidence (≥2%) in the Avastin plus FOLFOX4 vs FOLFOX4 groups, were diarrhea (18% vs 13%), nausea (12% vs 5%), vomiting (11% vs 4%), dehydration (10% vs 5%), ileus (4% vs 1%), neuropathy–sensory (17% vs 9%), neurologic–other (5% vs 3%), fatigue (19% vs 13%), abdominal pain (8% vs 5%), headache (3% vs 0%), hypertension (9% vs 2%), and hemorrhage (5% vs 1%)

• Grade 3–5 (nonhematologic) and grade 4–5 (hematologic) adverse events occurring at a ≥2% higher incidence in Avastin-treated patients vs controls were neutropenia (27% vs 17%), fatigue (16% vs 13%), hypertension (8% vs 0.7%), infection without neutropenia (7% vs 3%), venous thrombus/embolism (5% vs 3%), febrile neutropenia (5% vs 2%), pneumonitis/pulmonary infiltrates (5% vs 3%), infection with grade 3 or 4 neutropenia (4% vs 2%), hyponatremia (4% vs 1%), headache (3% vs 1%), and proteinuria (3% vs 0%)

• The most common grade 3–5 adverse events in AVOREN, occurring at a ≥2% higher incidence in Avastin-treated patients vs controls, were fatigue (13% vs 8%), asthenia (10% vs 7%), proteinuria (7% vs 0%), hypertension (6% vs 1%), and hemorrhage (3% vs 0.3%)

Please see full Prescribing Information, including Boxed WARNINGS for additional safety information.

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Herceptin (trastuzumab)

Adjuvant indications

Herceptin is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:

• As part of a treatment regimen containing doxorubicin, cyclophosphamide, and either paclitaxel or docetaxel
• With docetaxel and carboplatin
• As a single agent following multi-modality anthracycline-based therapy

* ER/PR-negative, tumor size >2 cm, age <35 years, or histological and/or nuclear grade 2 or 3.

Metastatic indications

Herceptin is indicated:

• In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer
• As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease

Boxed WARNINGS and Additional Important Safety Information

Herceptin administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction. Serious infusion reactions and pulmonary toxicity have occurred; fatal infusion reactions have been reported. Exacerbation of chemotherapy-induced neutropenia has also occurred. Herceptin can cause oligohydramnios and fetal harm when administered to a pregnant woman. The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.

Please see the Herceptin full prescribing information including Boxed WARNINGS and additional important safety information.

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Rituxan (rituximab)

INDICATIONS AND USAGE

Rituxan^® is indicated for the treatment of patients with:

• Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent
• Previously untreated follicular, CD20‑positive, B-cell NHL in combination with CVP chemotherapy
• Non-progressing (including stable disease), low‑grade, CD20‑positive, B‑cell NHL, as a single agent, after first‑line CVP chemotherapy
• Previously untreated diffuse large B‑cell, CD20‑positive, NHL in combination with CHOP or other anthracycline‑based chemotherapy regimens

BOXED WARNINGS and Additional Important Safety Information

The most important serious adverse reactions of Rituxan are fatal infusion reactions, tumor lysis syndrome (TLS), severe mucocutaneous reactions, progressive multifocal leukoencephalopathy (PML), hepatitis B reactivation with fulminant hepatitis, other viral infections, cardiovascular events, renal toxicity, and bowel obstruction and perforation. The most common adverse reactions of Rituxan (incidence ≥25%) observed in patients with NHL are infusion reactions, fever, chills, infection, asthenia, and lymphopenia.

Attention healthcare provider: Provide Medication Guide to patient prior to Rituxan infusion.

For additional safety information, please see the full prescribing information, including BOXED WARNINGS and Medication Guide.

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Tarceva (erlotinib)

Indication and Use in second-line Advanced NSCLC

Tarceva monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Results from two multicenter, placebo-controlled, randomized, Phase III trials conducted in first-line patients with locally advanced or metastatic NSCLC showed no clinical benefit with the concurrent administration of Tarceva with platinum-based chemotherapy, and its use is not recommended in that setting.

Indication and Use in first-line Advanced Pancreatic Cancer

Tarceva in combination with gemcitabine is indicated for first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.

Important Safety Information

There have been infrequent reports of serious Interstitial Lung Disease (ILD)-like events, including fatalities, in patients receiving Tarceva for treatment of NSCLC, pancreatic cancer or other advanced solid tumors. In the event of an acute onset of new or progressive, unexplained pulmonary symptoms such as dyspnea, cough and fever, Tarceva therapy should be interrupted pending diagnostic evaluation. If ILD is diagnosed, Tarceva should be discontinued and appropriate treatment instituted as needed.

Cases of hepatic failure, hepatorenal syndrome, acute renal failure (all including fatalities), and renal insufficiency have been reported during use of Tarceva. Treatment with Tarceva should be used with extra caution in patients with total bilirubin > 3 x ULN. Tarceva dosing should be interrupted or discontinued if changes in liver function are severe. Patients should be closely monitored during therapy with Tarceva.

Gastrointestinal perforation (including fatalities) has been reported in patients receiving Tarceva. Permanently discontinue Tarceva in patients who develop gastrointestinal perforation.

Bullous, blistering and exfoliative skin conditions have been reported including cases suggestive of Stevens-Johnson syndrome/toxic epidermal necrolysis, which in some cases were fatal. Interrupt or discontinue Tarceva treatment if the patient develops severe bullous, blistering or exfoliating conditions.

In the pancreatic cancer trial, other serious adverse reactions associated with Tarceva plus gemcitabine and which may have included fatalities, were myocardial infarction/ischemia, cerebrovascular accident and microangiopathic hemolytic anemia with thrombocytopenia.

Corneal perforation and ulceration have been reported during use of Tarceva. Interrupt or discontinue Tarceva therapy if patients present with acute/worsening ocular disorders such as eye pain.

When receiving Tarceva therapy, women should be advised against becoming pregnant or breastfeeding. Tarceva is pregnancy category D.

The most common adverse reactions in patients with NSCLC receiving Tarceva monotherapy 150 mg were mild to moderate rash and diarrhea. Severe rash and diarrhea (9% & 6% NCI-CTC Grades 3-4, respectively) were reported. Rash and diarrhea each resulted in dose reductions (6% and 1%, respectively) and discontinuation in 1% of Tarceva-treated patients during the single-agent Phase III trial.

The most common adverse reactions in patients with pancreatic cancer receiving Tarceva 100 mg plus gemcitabine were fatigue, rash, nausea, anorexia and diarrhea. Severe rash and diarrhea (5% and 5% NCI-CTC Grades 3-4, respectively) were reported. Rash and diarrhea each resulted in dose reductions in 2% of patients, and discontinuation in up to 1% of patients receiving Tarceva plus gemcitabine.

Please see the Tarceva full prescribing information for complete safety information.

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