For Patients and Caregivers

TECENTRIQ + Avastin® (bevacizumab) Offers a Same-Day Dosing Schedule

Choose consistent q3w combination infusions, or offer flexible TECENTRIQ dosing options (q4w, q3w, or q2w)1,11

TECENTRIQ + Avastin dosing schedule

Dosing information for Avastin is based on the IMbrave150 trial; TECENTRIQ was administered q3w in IMbrave150. Visualization of vials is illustrative and does not represent actual vial usage.
IV=intravenous; 4w=every 4 weeks; q3w=every 3 weeks; q2w=every 2 weeks.

  • TECENTRIQ should be administered first, followed by Avastin when administered on the same day
  • TECENTRIQ can be administered as 840 mg q2w, as 1200 mg q3w, or as 1680 mg q4w
  • Administer the initial infusion of TECENTRIQ over 60 minutes; if the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes
  • Do not administer TECENTRIQ as an IV push or bolus
  • Do not co-administer other drugs through the same IV line
  • Avastin is administered as an IV infusion at 15 mg/kg q3w
  • First infusion of Avastin: administer infusion over 90 minutes
  • Subsequent infusions: administer second infusion over 60 minutes if first infusion is tolerated. Administer all subsequent infusions over 30 minutes if second infusion over 60 minutes is tolerated
  • Refer to the Avastin Prescribing Information for Avastin dosage modifications for specific adverse reactions. No dose reductions for Avastin are recommended
Select Important Safety Information for Avastin11
  • An evaluation for the presence of varices is recommended within 6 months of initiation of Avastin in patients with HCC
  • There is lack of clinical data to support the safety of Avastin in patients with history or risk of variceal bleeding

Dosage modifications from the TECENTRIQ Prescribing Information1*

No dose reduction for TECENTRIQ is recommended. In general, withhold TECENTRIQ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue TECENTRIQ for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks of initiating steroids.

Dosage modifications for TECENTRIQ for adverse reactions that require management different from these general guidelines are summarized in the following table:

Adverse reaction
 Severity†
 Dosage modification
Pneumonitis
 Grade 2 
 Withhold‡
Grade 3 or 4
 Permanently discontinue
Colitis Grade 2 or 3 Withhold‡
Grade 4 Permanently discontinue
Hepatitis with no tumor involvement of the liver
 AST or ALT >3 and ≤8 times ULN
or
Total bilirubin >1.5 and ≤3 times ULN
 Withhold‡
AST or ALT >8 times ULN
or
Total bilirubin >3 times ULN

 Permanently discontinue
Hepatitis with tumor involvement of the liver§
 Baseline AST or ALT >1 and ≤3 times ULN and increases to >5 and ≤10 times ULN
or
Baseline AST or ALT >3 and ≤5 times ULN and increases to >8 and ≤10 times ULN
 Withhold‡
AST or ALT >10 times ULN
or
Total bilirubin >3 times ULN
 Permanently discontinue
Endocrinopathies
 Grade 3 or 4
 Withhold until clinically stable or permanently discontinue depending on severity
Nephritis with renal dysfunction
 Grade 2 or 3 increased blood creatinine
 Withhold‡
Grade 4 increased blood creatinine
 Permanently discontinue
Exfoliative dermatologic conditions
 Suspected SJS, TEN, or DRESS
 Withhold
Confirmed SJS, TEN, or DRESS Permanently discontinue
Myocarditis Grade 2, 3, or 4 Permanently discontinue
Neurological toxicities Grade 2 Withhold‡
Grade 3 or 4 Permanently discontinue
Infusion-related reactions
 Grade 1 or 2
 Interrupt or slow the rate of infusion
Grade 3 or 4
 Permanently discontinue 

ALT=alanine aminotransferase; AST=aspartate aminotransferase; DRESS=drug rash with eosinophilia and systemic symptoms; SJS=Stevens-Johnson syndrome; TEN=toxic epidermal necrolysis; ULN=upper limit of normal.
*Refer to the Prescribing Information for other medications for dosage modification and AR management.
†Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI CTCAE v4.0).
‡Resume in patients with complete or partial resolution (grade 0-1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids.
§If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue TECENTRIQ based on recommendations for hepatitis with no liver involvement.

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Indication

TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy.

Serious Adverse Reactions
Please refer to the full Prescribing Information for important dose management information specific to adverse reactions.

Severe and Fatal Immune-Mediated Adverse Reactions
TECENTRIQ is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. The following immune-mediated adverse reactions may not include all possible severe and fatal immune-mediated reactions.

Immune-mediated adverse reactions can occur in any organ system or tissue and at any time after starting a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, they can also manifest after discontinuation of treatment.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue TECENTRIQ depending on severity. In general, if TECENTRIQ requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less, then initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

  • TECENTRIQ can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation
  • Immune-mediated pneumonitis occurred in 3% (83/2616) of patients receiving TECENTRIQ as a single agent, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.8%), and Grade 2 (1.1%) adverse reactions. Pneumonitis led to permanent discontinuation of TECENTRIQ in 0.5% and withholding of TECENTRIQ in 1.5% of patients. Systemic corticosteroids were required in 55% (46/83) of patients with pneumonitis

Immune-Mediated Colitis

  • TECENTRIQ can cause immune-mediated colitis. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal (GI) bleeding. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
  • Immune-mediated colitis occurred in 1% (26/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (0.5%) and Grade 2 (0.3%) adverse reactions. Colitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.5% of patients. Systemic corticosteroids were required in 50% (13/26) of patients with colitis. Colitis resolved in 73% of the 26 patients. Of the 12 patients in whom TECENTRIQ was withheld for colitis, 8 reinitiated treatment with TECENTRIQ after symptom improvement; of these, 25% had recurrence of colitis

Immune-Mediated Hepatitis

  • TECENTRIQ can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.8% (48/2616) of patients receiving TECENTRIQ as a single agent, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.5%), and Grade 2 (0.5%) adverse reactions. Hepatitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.2% of patients. Systemic corticosteroids were required in 25% (12/48) of patients with hepatitis. Hepatitis resolved in 50% of the 48 patients. Of the 6 patients in whom TECENTRIQ was withheld for hepatitis, 4 reinitiated treatment with TECENTRIQ after symptom improvement; of these, none had recurrence of hepatitis

Immune-Mediated Endocrinopathies
Adrenal Insufficiency

  • TECENTRIQ can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated
  • Adrenal insufficiency occurred in 0.4% (11/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (<0.1%) and Grade 2 (0.2%) adverse reactions. Adrenal insufficiency led to permanent discontinuation of TECENTRIQ in 1 patient and withholding of TECENTRIQ in 1 patient. Systemic corticosteroids were required in 81% (9/11) of patients with adrenal insufficiency; of these, 3 patients remained on systemic corticosteroids. The single patient in whom TECENTRIQ was withheld for adrenal insufficiency did not reinitiate TECENTRIQ

Hypophysitis

  • TECENTRIQ can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated
  • Hypophysitis occurred in <0.1% (2/2616) of patients receiving TECENTRIQ as a single agent, including Grade 2 (1 patient, <0.1%) adverse reactions. Hypophysitis led to permanent discontinuation of TECENTRIQ in 1 patient and no patients required withholding of TECENTRIQ. Systemic corticosteroids were required in 50% (1/2) of patients with hypophysitis. Hypophysitis did not resolve in these 2 patients

Thyroid Disorders

  • TECENTRIQ can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or medical management for hyperthyroidism as clinically indicated
  • Thyroiditis occurred in 0.2% (4/2616) of patients receiving TECENTRIQ as a single agent, including Grade 2 (<0.1%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 1 patient. Hormone replacement therapy was required in 75% (3/4) of patients with thyroiditis. Systemic corticosteroids were required in 25% (1/4) of patients with thyroiditis. Thyroiditis resolved in 50% of patients. The single patient in whom TECENTRIQ was withheld for thyroiditis reinitiated TECENTRIQ; this patient did not have recurrence of thyroiditis
  • Hyperthyroidism occurred in 0.8% (21/2616) of patients receiving TECENTRIQ as a single agent, including Grade 2 (0.4%) adverse reactions. Hyperthyroidism did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 0.1% of patients. Antithyroid therapy was required in 29% (6/21) of patients with hyperthyroidism. Of these 6 patients, the majority remained on antithyroid treatment. Of the 3 patients in whom TECENTRIQ was withheld for hyperthyroidism, 1 patient reinitiated TECENTRIQ; this patient did not have recurrence of hyperthyroidism
  • Hypothyroidism occurred in 4.9% (128/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (0.2%) and Grade 2 (3.4%) adverse reactions. Hypothyroidism did not lead to permanent discontinuation of TECENTRIQ in any of these patients, but led to withholding of TECENTRIQ in 0.6% of patients. Hormone replacement therapy was required in 81% (104/128) of patients with hypothyroidism. The majority of patients with hypothyroidism remained on thyroid hormone replacement. Of the 17 patients in whom TECENTRIQ was withheld for hypothyroidism, 8 reinitiated TECENTRIQ after symptom improvement

Type 1 Diabetes Mellitus, Which Can Present With Diabetic Ketoacidosis

  • Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated
  • Type 1 diabetes mellitus occurred in 0.3% (7/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (0.2%) and Grade 2 (<0.1%) adverse reactions. Type 1 diabetes mellitus led to permanent discontinuation of TECENTRIQ in 1 patient and withholding of TECENTRIQ in 2 patients. Treatment with insulin was required for all patients with confirmed Type 1 diabetes mellitus and insulin therapy was continued long-term. Of the 2 patients in whom TECENTRIQ was withheld for Type 1 diabetes mellitus, both reinitiated TECENTRIQ treatment

Immune-Mediated Nephritis With Renal Dysfunction

  • TECENTRIQ can cause immune-mediated nephritis
  • Immune-mediated nephritis with renal dysfunction occurred in <0.1% (1/2616) of patients receiving TECENTRIQ as a single agent, and this adverse reaction was a Grade 3 (<0.1%) adverse reaction. Nephritis led to permanent discontinuation of TECENTRIQ in this patient. This patient required systemic corticosteroids. In this patient, nephritis did not resolve

Immune-Mediated Dermatologic Adverse Reactions

  • TECENTRIQ can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), DRESS, and toxic epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes 
  • Immune-mediated dermatologic adverse reactions occurred in 0.6% (15/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (<0.1%) and Grade 2 (0.2%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TECENTRIQ in 0.1% and withholding of TECENTRIQ in 0.2% of patients. Systemic corticosteroids were required in 20% (3/15) of patients with dermatologic adverse reactions. Dermatologic adverse reactions resolved in 87% of the 15 patients. Of the 4 patients in whom TECENTRIQ was withheld for immune-mediated dermatologic adverse reactions, none reinitiated TECENTRIQ

Other Immune-Mediated Adverse Reactions

  • The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received TECENTRIQ or were reported with the use of other PD-1/PD-L1 blocking antibodies
    • Cardiac/Vascular: Myocarditis, pericarditis, vasculitis
    • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy
    • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss
    • Gastrointestinal: Pancreatitis to include increases in serum amylase and lipase levels, gastritis, duodenitis
    • Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic
    • Endocrine: Hypoparathyroidism
    • Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection

Infusion-Related Reactions

  • TECENTRIQ can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue TECENTRIQ based on the severity. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses
  • Infusion-related reactions occurred in 1.3% of patients receiving TECENTRIQ as a single agent, including Grade 3 (0.2%) reactions
  • The frequency and severity of infusion-related reactions were similar across the recommended dose range

Complications of Allogeneic HSCT After PD-1/PD-L1 Inhibitors

  • Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody
  • Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
  • These complications may occur despite intervening therapy between PD-1/PD-L1 blockage and allogeneic HSCT
  • Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefits versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT

Embryo-Fetal Toxicity

  • Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. There are no available data on the use of TECENTRIQ in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus, resulting in fetal death
  • Verify pregnancy status of females of reproductive potential prior to initiating TECENTRIQ. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose

Use In Specific Populations
Nursing Mothers

  • There is no information regarding the presence of TECENTRIQ in human milk, the effects on the breastfed infant, or the effects on milk production. As human IgG is excreted in human milk, the potential for absorption and harm to the infant is unknown
  • Because of the potential for serious adverse reactions in breastfed infants from TECENTRIQ, advise female patients not to breastfeed while taking TECENTRIQ and for at least 5 months after the last dose

Fertility

  • Based on animal studies, TECENTRIQ may impair fertility in females of reproductive potential while receiving treatment

Most Common Adverse Reactions
The most common adverse reactions (rate ≥20%) in patients who received TECENTRIQ in combination with bevacizumab for HCC were hypertension (30%), fatigue/asthenia (26%), and proteinuria (20%).

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full TECENTRIQ Prescribing Information and full Avastin Prescribing Information for additional Important Safety Information.

    • TECENTRIQ Prescribing Information. Genentech, Inc.

      TECENTRIQ Prescribing Information. Genentech, Inc.

    • Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed April 29, 2021. To view the most recent and complete version of the guideline, go online to www.NCCN.org.

      Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Hepatobiliary Cancers V.2.2021. © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed April 29, 2021. To view the most recent and complete version of the guideline, go online to www.NCCN.org.

    • Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-1905.

      Finn RS, Qin S, Ikeda M, et al; IMbrave150 Investigators. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-1905.

    • Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival data from a global, randomized, open-label phase III study of atezolizumab + bevacizumab vs sorafenib in patients with unresectable hepatocellular carcinoma. Paper presented at: 2021 Gastrointestinal Cancers Symposium (ASCO GI); January 15-17, 2021; virtual conference.

      Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival data from a global, randomized, open-label phase III study of atezolizumab + bevacizumab vs sorafenib in patients with unresectable hepatocellular carcinoma. Paper presented at: 2021 Gastrointestinal Cancers Symposium (ASCO GI); January 15-17, 2021; virtual conference.

    • Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39:267.

      Finn RS, Qin S, Ikeda M, et al. IMbrave150: updated overall survival (OS) data from a global, randomized, open-label phase III study of atezolizumab (atezo) + bevacizumab (bev) versus sorafenib (sor) in patients (pts) with unresectable hepatocellular carcinoma (HCC). J Clin Oncol. 2021;39:267.

    • Data on file. Clinical Study Report YO40245. Genentech, Inc.

      Data on file. Clinical Study Report YO40245. Genentech, Inc.

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      Li D, Sedano S, Allen R, Gong J, Cho M, Sharma S. Current treatment landscape for advanced hepatocellular carcinoma: patient outcomes and the impact on quality of life. Cancers. 2019;11:841.

    • Kudo M, Finn R, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non­inferiority trial. Lancet. 2018;391:1163-1173.

      Kudo M, Finn R, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non­inferiority trial. Lancet. 2018;391:1163-1173.

    • Data on file. Study Protocol YO40245. Genentech, Inc.

      Data on file. Study Protocol YO40245. Genentech, Inc.

    • Data on file. Roche.

      Data on file. Roche.

    • Avastin (bevacizumab) Prescribing Information. Genentech, Inc.

      Avastin (bevacizumab) Prescribing Information. Genentech, Inc.