ASCO Connection

September 2017

Issue link: http://read.uberflip.com/i/869954

Contents of this Issue

Navigation

Page 66 of 67

TECENTRIQ ® [atezolizumab] Initial U.S. Approval: 2016 This is a brief summary of information about TECENTRIQ. Before prescribing, please see full Prescribing Information. 1 INDICATIONS AND USAGE 1.1 Locally Advanced or Metastatic Urothelial Carcinoma TECENTRIQ (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who: • are not eligible for cisplatin-containing chemotherapy, or • have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14.1)]. 1.2 Metastatic Non-Small Cell Lung Cancer TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ [see Clinical Studies (14.2)]. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Immune-Related Pneumonitis Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs with radiographic imaging and for symptoms of pneumonitis. Administer steroids at a dose of 1 to 2 mg/kg/day prednisone equivalents for Grade 2 or greater pneumonitis, followed by corticosteroid taper. Withhold TECENTRIQ until resolution for Grade 2 pneumonitis. Permanently discontinue TECENTRIQ for Grade 3 or 4 pneumonitis [see Dosage and Administration (2.2)]. Across clinical trials, 2.6% (51/1978) of patients developed pneumonitis. Fatal pneumonitis occurred in two patients. Urothelial Carcinoma In 523 patients with urothelial carcinoma who received TECENTRIQ, pneumonitis occurred in six (1.1%) patients. Of these patients, there was one patient with fatal pneumonitis, one patient with Grade 3, three patients with Grade 2, and one patient with Grade 1 pneumonitis. TECENTRIQ was held in all cases. Pneumonitis resolved in three patients. The median time to onset was 2.6 months (range: 15 days to 4.2 months). The median duration was 15 days (range: 6 days to 3.1+ months). Immune-mediated pneumonitis occurred in 5 (1.0%) patients. NSCLC In 1027 patients with NSCLC who received TECENTRIQ, pneumonitis occurred in 38 (3.7%) patients. Of these patients, there was one patient with fatal pneumonitis, two patients with Grade 4, thirteen patients with Grade 3, eleven patients with Grade 2, and eleven patients with Grade 1 pneumonitis. TECENTRIQ was held in 24 patients and 21 patients were treated with corticosteroids. Pneumonitis resolved in 26 of the 38 patients. The median time to onset was 3.3 months (range: 3 days to 18.7 months). The median duration was 1.4 months (range: 0 days to 12.6+ months). 5.2 Immune-Related Hepatitis Immune-mediated hepatitis, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ treatment. Liver test abnormalities occurred in patients who received TECENTRIQ. Monitor patients for signs and symptoms of hepatitis. Monitor AST, ALT, and bilirubin prior to and periodically during treatment with TECENTRIQ. Administer corticosteroids at a dose of 1–2 mg/kg/day prednisone equivalents for Grade 2 or greater transaminase elevations, with or without concomitant elevation in total bilirubin, followed by corticosteroid taper. Withhold TECENTRIQ for Grade 2 and permanently discontinue TECENTRIQ for Grade 3 or 4 immune-mediated hepatitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials (n=1978), Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.3%), and total bilirubin (1.6%). Urothelial Carcinoma In patients with urothelial carcinoma (n=523), Grade 3 or 4 elevation occurred in ALT (2.5%), AST (2.5%), and total bilirubin (2.1%). Immune-mediated hepatitis occurred in 1.3% (7/523) of patients. Of these cases, one patient died from hepatitis, five patients had Grade 3, and one patient had Grade 2 hepatitis. The median time to onset was 1.1 months (range: 0.4 to 7.7 months). TECENTRIQ was temporarily interrupted in four patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ. NSCLC In patients with NSCLC, Grade 3 or 4 elevation occurred in ALT (1.4%), AST (1.3%), and total bilirubin (0.6%). Immune-mediated hepatitis occurred in 0.9% (9/1027) of patients. Of these nine patients, one patient had Grade 4, four patients had Grade 3, three patients had Grade 2, and one patient had Grade 1 immune-mediated hepatitis. The median time to onset was 28 days (range: 15 days to 4.2 months). TECENTRIQ was temporarily interrupted in seven patients; none of these patients developed recurrence of hepatitis after resuming TECENTRIQ. 5.3 Immune-Related Colitis Immune-mediated colitis or diarrhea, defined as requiring use of corticosteroids and with no clear alternate etiology, occurred in patients receiving TECENTRIQ. Monitor patients for signs and symptoms of diarrhea or colitis. Withhold treatment with TECENTRIQ for Grade 2 diarrhea or colitis. If symptoms persist for longer than 5 days or recur, administer 1–2 mg/kg prednisone or equivalent per day. Withhold treatment with TECENTRIQ for Grade 3 diarrhea or colitis. Treat with IV methylprednisolone 1–2 mg/kg per day and convert to oral steroids once the patient has improved. For both Grade 2 and Grade 3 diarrhea or colitis, when symptoms improve to Grade 0 or Grade 1, taper steroids over ≥ 1 month. Resume treatment with TECENTRIQ if the event improves to Grade 0 or 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤ 10 mg oral prednisone per day. Permanently discontinue TECENTRIQ for Grade 4 diarrhea or colitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials, colitis or diarrhea occurred in 19.7% (389/1978) of all patients. Urothelial Carcinoma In 523 patients with urothelial carcinoma who received TECENTRIQ, colitis or diarrhea occurred in 98 (18.7%) patients. Ten patients (1.9%) developed Grade 3 or 4 diarrhea. Four patients (0.8%) had immune-mediated colitis or diarrhea with a median time to onset of 1.7 months (range: 1.1 to 3.1 months). Immune-mediated colitis resolved with corticosteroid administration in three of these patients, while the other patient died without resolution of colitis in the setting of diarrhea-associated renal failure. NSCLC In 1027 patients with NSCLC who received TECENTRIQ, colitis or diarrhea occurred in 198 (19.3%) patients. Twelve patients (1.2%) developed Grade 3 colitis or diarrhea. Five patients (0.5%) had immune-mediated colitis or diarrhea with a median time to onset of 21 days (range: 12 days to 3.4 months). Of these patients, one had Grade 3, two had Grade 2, and two had Grade 1 immune-mediated colitis or diarrhea. Immune-mediated colitis or diarrhea resolved with corticosteroid administration in four of these patients, while the fifth patient died due to disease progression prior to resolution of colitis. 5.4 Immune-Related Endocrinopathies Immune-related thyroid disorders, adrenal insufficiency, and type 1 diabetes mellitus, including diabetic ketoacidosis, have occurred in patients receiving TECENTRIQ. Monitor patients for clinical signs and symptoms of endocrinopathies. Hypophysitis Hypophysitis occurred in 0.2% (1/523) of patients with urothelial cancer receiving TECENTRIQ. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids and hormone replacement as clinically indicated. Withhold TECENTRIQ for Grade 2 or Grade 3 and permanently discontinue for Grade 4 hypophysitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Thyroid Disorders Thyroid function was assessed routinely only at baseline and the end of the study. Monitor thyroid function prior to and periodically during treatment with TECENTRIQ. Asymptomatic patients with abnormal thyroid function tests can receive TECENTRIQ. For symptomatic hypothyroidism, withhold TECENTRIQ and initiate thyroid hormone replacement as needed. Manage isolated hypothyroidism with replacement therapy and without corticosteroids. For symptomatic hyperthyroidism, withhold TECENTRIQ and initiate an anti-thyroid drug as needed. Resume treatment with TECENTRIQ when symptoms of hypothyroidism or hyperthyroidism are controlled and thyroid function is improving [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials, hypothyroidism and hyperthyroidism occurred in 3.9% (77/1978) and 1.0% (20/1978) of patients, respectively. Urothelial Carcinoma In 523 patients with urothelial carcinoma who received TECENTRIQ, hypothyroidism occurred in 2.5% (13/523). One patient had Grade 3 and twelve patients had Grade 1–2 hypothyroidism. The median time to first onset was 5.4 months (range: 21 days to 11.3 months). Thyroid stimulating hormone (TSH) was elevated and above the patient's baseline in 16% (21/131) of patients with a follow-up measurement. Hyperthyroidism occurred in 0.6% (3/523) of patients with urothelial carcinoma. Of the three urothelial carcinoma patients, one patient had Grade 2 and two patients had Grade 1 hyperthyroidism. The median time to onset was 3.2 months (range: 1.4 to 5.8 months). TSH was decreased and below the patient's baseline in 3.8% (5/131) of patients with a follow-up measurement. NSCLC In 1027 patients with NSCLC who received TECENTRIQ, hypothyroidism occurred in 4.2% (43/1027). Three patients had Grade 3 and forty patients had Grade 1–2 hypothyroidism. The median time to onset was 4.8 months (range 15 days to 31 months.) TSH was elevated and above the patient's baseline in 17% (54/315) of patients with follow-up measurement. Hyperthyroidism occurred in 1.1% (11/1027) of patients with NSCLC. Eight patients had Grade 2 and three patients had Grade 1 hyperthyroidism. The median time to onset was 4.9 months (range: 21 days to 31 months). TSH was decreased and below the patient's baseline in 7.6% (24/315) of patients with a follow-up measurement. Adrenal Insufficiency Adrenal insufficiency occurred in 0.4% (7/1978) of patients across clinical trials, including two patients with Grade 3, four patients with Grade 2, and one patient with Grade 1. Adrenal insufficiency resolved in two patients. For symptomatic adrenal insufficiency, withhold TECENTRIQ and administer methylprednisolone 1–2 mg/kg per day IV followed by oral prednisone 1–2 mg/kg per day or equivalent once symptoms improve. Start steroid taper when symptoms improve to ≤ Grade 1 and taper steroids over ≥ 1 month. Resume treatment with TECENTRIQ if the event improves to ≤ Grade 1 within 12 weeks and corticosteroids have been reduced to the equivalent of ≤ 10 mg oral prednisone per day and the patient is stable on replacement therapy, if required [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Diabetes Mellitus New onset diabetes with ketoacidosis has occurred in patients receiving TECENTRIQ. Diabetes mellitus without an alternative etiology occurred in one (0.2%) patient with urothelial carcinoma and three (0.3%) patients with NSCLC. Initiate treatment with insulin for type 1 diabetes mellitus. For ≥ Grade 3 hyperglycemia (fasting glucose >250–500 mg/dL), withhold TECENTRIQ. Resume treatment with TECENTRIQ when metabolic control is achieved on insulin replacement therapy [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. 5.5 Other Immune-Related Adverse Reactions Other immune-related adverse reactions including meningoencephalitis, myasthenic syndrome/ myasthenia gravis, Guillain-Barré, ocular inflammatory toxicity, and pancreatitis, including increases in serum amylase and lipase levels, have occurred in ≤ 1.0% of patients treated with TECENTRIQ. Meningitis / Encephalitis Monitor patients for clinical signs and symptoms of meningitis or encephalitis. Permanently discontinue TECENTRIQ for any grade of meningitis or encephalitis. Treat with IV steroids (1–2 mg/kg/day methylprednisolone or equivalent) and convert to oral steroids (prednisone 60 mg/day or equivalent) once the patient has improved. When symptoms improve to ≤ Grade 1, taper steroids over ≥ 1 month [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Motor and Sensory Neuropathy Monitor patients for symptoms of motor and sensory neuropathy. Permanently discontinue TECENTRIQ for any grade of myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome. Institute medical intervention as appropriate. Consider initiation of systemic corticosteroids at a dose of 1–2 mg/kg/day prednisone [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Pancreatitis Symptomatic pancreatitis without an alternative etiology occurred in 0.1% (2/1978) of patients across clinical trials. Monitor patients for signs and symptoms of acute pancreatitis. Withhold TECENTRIQ for ≥ Grade 3 serum amylase or lipase levels (> 2.0 ULN), or Grade 2 or 3 pancreatitis. Treat with 1−2 mg/kg IV methylprednisolone or equivalent per day. Once symptoms improve, follow with 1−2 mg/kg of oral prednisone or equivalent per day. Resume treatment with TECENTRIQ when serum amylase and lipase levels improve to ≤ Grade 1 within 12 weeks or symptoms of pancreatitis have resolved, and corticosteroids have been reduced to ≤ 10 mg oral prednisone or equivalent per day. Permanently discontinue TECENTRIQ for Grade 4 or any grade of recurrent pancreatitis [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. 5.6 Infection Severe infections, including sepsis, herpes encephalitis, and mycobacterial infection leading to retroperitoneal hemorrhage occurred in patients receiving TECENTRIQ. Monitor patients for signs and symptoms of infection and treat with antibiotics for suspected or confirmed bacterial infections. Withhold TECENTRIQ for ≥ Grade 3 infection [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. Across clinical trials, infections occurred in 38.4% (759/1978) of patients. Urothelial Carcinoma In 523 patients with urothelial carcinoma who received TECENTRIQ, infection occurred in 197 (37.7%) patients. Grade 3 or 4 infection occurred in sixty (11.5%) patients, while three patients died due to infections. Urinary tract infections were the most common cause of Grade 3 or higher infection, occurring in 37 (7.1%) patients. NSCLC In Study 3, a randomized trial in patients with NSCLC, infections were more common in patients treated with TECENTRIQ (43%) compared with those treated with docetaxel (34%). Grade 3 or 4 infections occurred in 9.2% of patients treated with TECENTRIQ compared with 2.2% in patients treated with docetaxel. Two patients (1.4%) treated with TECENTRIQ and three patients (2.2%) treated with docetaxel died due to infection. Pneumonia was the most common cause of Grade 3 or higher infection, occurring in 7.7% of patients treated with TECENTRIQ. 5.7 Infusion-Related Reactions Severe infusion reactions have occurred in patients in clinical trials of TECENTRIQ. Infusion-related reactions occurred in 1.3% (25/1978) of patients across clinical trials, 1.7% (9/523) of patients with urothelial carcinoma, and 1.6% (16/1027) of patients with NSCLC. Interrupt or slow the rate of infusion in patients with mild or moderate infusion reactions. Permanently discontinue TECENTRIQ in patients with Grade 3 or 4 infusion reactions [see Dosage and Administration (2.2) and Adverse Reactions (6.1)]. 5.8 Embryo-Fetal Toxicity Based on its mechanism of action, TECENTRIQ can cause fetal harm when administered to a pregnant woman. 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. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, advise the patient of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ and for at least 5 months after the last dose [see Use in Specific Populations (8.1, 8.3)].

Articles in this issue

Archives of this issue

view archives of ASCO Connection - September 2017