Keytruda ( Pembrolizumab ) is indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following Ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.
This indication is approved under accelerated approval based on tumor response rate and durability of response.
An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Selected important safety information
Pneumonitis occurred in 12 ( 2.9% ) of 411 patients with advanced melanoma receiving Keytruda, including grade 2 or 3 cases in 8 ( 1.9% ) and 1 ( 0.2% ) patients, respectively. Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for grade 2 or greater pneumonitis. Withhold Keytruda for grade 2; permanently discontinue Keytruda for grade 3 or 4 pneumonitis.
Colitis ( including microscopic colitis ) occurred in 4 ( 1% ) of 411 patients, including grade 2 or 3 cases in 1 ( 0.2% ) and 2 ( 0.5% ) patients respectively, receiving Keytruda. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for grade 2 or greater colitis. Withhold Keytruda for grade 2 or 3; permanently discontinue Keytruda for grade 4 colitis.
Hepatitis ( including autoimmune hepatitis ) occurred in 2 ( 0.5% ) of 411 patients, including a grade 4 case in 1 ( 0.2% ) patient, receiving Keytruda. Monitor patients for changes in liver function. Administer corticosteroids for grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue Keytruda.
Hypophysitis occurred in 2 ( 0.5% ) of 411 patients, including a grade 2 case in 1 and a grade 4 case in 1 ( 0.2% each ) patient, receiving Keytruda. Monitor for signs and symptoms of hypophysitis. Administer corticosteroids for grade 2 or greater hypophysitis. Withhold Keytruda for grade 2; withhold or discontinue for grade 3; and permanently discontinue Keytruda for grade 4 hypophysitis.
Nephritis occurred in 3 ( 0.7% ) patients receiving Keytruda, consisting of one case of grade 2 autoimmune nephritis ( 0.2% ) and two cases of interstitial nephritis with renal failure ( 0.5% ), one grade 3 and one grade 4. Monitor patients for changes in renal function. Administer corticosteroids for grade 2 or greater nephritis. Withhold Keytruda for grade 2; permanently discontinue Keytruda for grade 3 or 4 nephritis.
Hyperthyroidism occurred in 5 ( 1.2% ) of 411 patients, including grade 2 or 3 cases in 2 ( 0.5% ) and 1 ( 0.2% ) patients respectively, receiving Keytruda.
Hypothyroidism occurred in 34 ( 8.3% ) of 411 patients, including a grade 3 case in 1 ( 0.2% ) patient, receiving Keytruda.
Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function ( at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation ) and for clinical signs and symptoms of thyroid disorders. Administer corticosteroids for grade 3 or greater hyperthyroidism. Withhold Keytruda for grade 3; permanently discontinue Keytruda for grade 4 hyperthyroidism.
Isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids.
Other clinically important immune-mediated adverse reactions can occur. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of patients treated with Keytruda: exfoliative dermatitis, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, adrenal insufficiency, myasthenic syndrome, optic neuritis, and rhabdomyolysis.
For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold Keytruda and administer corticosteroids.
Upon improvement of the adverse reaction to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.
Restart Keytruda if the adverse reaction remains at grade 1 or less. Permanently discontinue Keytruda for any severe or grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
Based on its mechanism of action, Keytruda may cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of Keytruda.
For the treatment of advanced melanoma, Keytruda was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied.
Serious adverse reactions occurred in 36% of patients receiving Keytruda. The most frequent serious adverse drug reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis.
The most common adverse reactions ( reported in greater than or equal to 20% of patients ) were fatigue ( 47% ), cough ( 30% ), nausea ( 30% ), pruritus ( 30% ), rash ( 29% ), decreased appetite ( 26% ), constipation ( 21% ), arthralgia ( 20% ), and diarrhea ( 20% ). ( Xagena )
Source: Merck, 2015