New Drugs / Therapies

New Drugs / Therapies

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Corporate Member Merck- Update

May, 2019

Merck is pleased to announce that KEYTRUDA, as a single agent, has been approved by the FDA for the first-line treatment of patients with stage III non–small cell lung cancer (NSCLC) who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

PD-L1 diagnostic testing is required prior to initiating treatment with KEYTRUDA in these patients

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after 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 KEYTRUDA.

FDA=Food and Drug Administration; PD-L1=programmed death ligand 1.

Selected Safety Information for KEYTRUDA® (pembrolizumab) injection 100 mg

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. For more information regarding immune-mediated adverse reactions, please read the additional Selected Safety Information below.

KEYNOTE-042
First-line Treatment of Metastatic NSCLC as a Single Agent

The efficacy of KEYTRUDA was investigated in KEYNOTE-042 (NCT02220894) a randomized, multicenter, open-label, active-controlled trial conducted in 1274 patients with stage III NSCLC who were not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, whose tumors expressed PD-L1 (TPS ≥1%) by an immunohistochemistry assay using the PD-L1 IHC 22C3 pharmDx Kit, and who had not received prior systemic treatment for metastatic NSCLC. Patients with EGFR or ALK genomic tumor aberrations; autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of radiation in the thoracic region within the prior 26 weeks of initiation of study were ineligible. Randomization was stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1), histology (squamous vs. nonsquamous), geographic region (East Asia vs. non-East Asia), and PD-L1 expression (TPS ≥50% vs. TPS 1 to 49%). Patients were randomized (1:1) to receive KEYTRUDA 200 mg intravenously every 3 weeks or investigator’s choice of either of the following platinum-containing chemotherapy regimens:

Pemetrexed 500 mg/m2 every 3 weeks and carboplatin area under the curve (AUC) 5 to 6 mg/mL/min every 3 weeks on Day 1 for a maximum of 6 cycles followed by optional pemetrexed 500 mg/m2 every 3 weeks for patients with nonsquamous histologies;
Paclitaxel 200 mg/m2 every 3 weeks and carboplatin AUC 5 to 6 mg/mL/min every 3 weeks on Day 1 for a maximum of 6 cycles followed by optional pemetrexed 500 mg/m2 every 3 weeks for patients with nonsquamous histologies.

Treatment with KEYTRUDA continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease, unacceptable toxicity, or a maximum of 24 months. Administration of KEYTRUDA was permitted beyond RECIST-defined disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. Treatment with KEYTRUDA could be reinitiated at the time of subsequent disease progression and administered for up to 12 months. Assessment of tumor status was performed every 9 weeks. The main efficacy outcome measure was overall survival (OS) in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC. Additional efficacy outcome measures were progression-free survival (PFS) and overall response rate (ORR) in the subgroup of patients with TPS ≥50% NSCLC, the subgroup of patients with TPS ≥20% NSCLC, and the overall population with TPS ≥1% NSCLC as assessed by a blinded independent central radiologists’ (BICR) review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

The study population characteristics were: median age of 63 years (range: 25 to 90), 45% age 65 or older; 71% male; 64% White, 30% Asian, and 2% Black. Nineteen percent were Hispanic or Latino. Sixty-nine percent had ECOG performance status of 1; 39% with squamous and 61% with nonsquamous histology; 87% with M1 disease and 13% with Stage IIIA (2%) or Stage IIIB (11%) who were not candidates for surgical resection or definitive chemoradiation per investigator assessment; and 5% with treated brain metastases at baseline. Forty-seven percent of patients had TPS ≥50% NSCLC and 53% had TPS 1 to 49% NSCLC.

The trial demonstrated a statistically significant improvement in OS for patients (PD-L1 TPS ≥50%, TPS ≥20%, TPS ≥1%) randomized to KEYTRUDA as compared with chemotherapy. The table below summarizes the efficacy results in the subgroup of patients with TPS ≥50% and in all randomized patients with TPS ≥1%.

Efficacy Results of All Randomized Patients (TPS ≥1% and TPS ≥50%) in KEYNOTE-042

 

TPS ≥1%

TPS ≥50%

Endpoint

KEYTRUDA
200 mg every 3 weeks n=637

Chemotherapy

n=637

KEYTRUDA
200 mg every 3 weeks n=299

Chemotherapy

n=300

OS

 

Number of events (%)

371 (58%)

438 (69%)

157 (53%)

199 (66%)

Median in months (95%  CI)

16.7 (13.9, 19.7)

12.1 (11.3, 13.3)

20.0 (15.4, 24.9)

12.2 (10.4, 14.2)

Hazard ratio* (95% CI)

0.81 (0.71, 0.93)

0.69 (0.56, 0.85)

p-Value†

0.0036

0.0006

PFS

 

Number of events (%)

507 (80%)

506 (79%)

221 (74%)

233 (78%)

Median in months (95%  CI)

5.4 (4.3, 6.2)

6.5 (6.3, 7.0)

7.1 (5.9, 9.0)

6.4 (6.1, 6.9)

Hazard ratio*‡ (95% CI)

1.07
(0.94, 1.21)

0.81
(0.67, 0.99)

p-Value†

–‡

NS§

Objective Response Rate

 

ORR‡ (95% CI)

27% (24, 31)

27% (23, 30)

39% (33.9, 45.3)

32% (26.8, 37.6)

Complete response
rate

0.5%

0.5%

0.7%

0.3%

Partial response rate

27%

26%

39%

32%

Duration of Response

 

 

% with duration ≥12 months¶

47%

16%

42%

17%

% with duration ≥18 months¶

26%

6%

25%

5%

*Based on the stratified Cox proportional hazard model
†Based on a stratified log-rank test; compared to a p-Value boundary of 0.0291
‡Not evaluated for statistical significance as a result of the sequential testing procedure for the secondary endpoints
§Not significant compared to a p-Value boundary of 0.0291
¶Based on observed duration of response
CI=confidence interval.

The results of all efficacy outcome measures in the subgroup of patients with PD-L1 TPS ≥20% NSCLC were intermediate between the results of those with PD-L1 TPS ≥1% and those with PD-L1 TPS ≥50%. In a pre-specified exploratory subgroup analysis for patients with TPS 1-49% NSCLC, the median OS was 13.4 months (95% CI: 10.7, 18.2) for the pembrolizumab group and 12.1 months (95% CI: 11.0, 14.0) in the chemotherapy group, with a hazard ratio of 0.92 (95% CI: 0.77, 1.11).

Recommended Dosage for NSCLC

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, administer KEYTRUDA prior to chemotherapy when given on the same day. Refer to the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA for recommended dosing information, as appropriate.

Selected Safety Information for KEYTRUDA® (pembrolizumab) injection 100 mg (continued)

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). 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 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). 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.

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). 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.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.
Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. 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 to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma (cHL), and postmarketing use.
Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.
In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a programmed death receptor-1 (PD-1) or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (≥20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).
In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.
In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (≥20%) was fatigue (25%).
In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (≥20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Before prescribing KEYTRUDA® (pembrolizumab), please read the Prescribing Information.
The Medication Guide also is available.

Corporate Member Merck- Update

KEYTRUDA
May, 2019

Merck is pleased to announce that KEYTRUDA, in combination with axitinib, has been approved by the FDA for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

PD-L1 diagnostic testing is not required prior to initiating treatment with KEYTRUDA in these patients

FDA=Food and Drug Administration; PD-L1=programmed death ligand 1.

Selected Safety Information for KEYTRUDA® (pembrolizumab) injection 100 mg

Immune-mediated adverse reactions, which may be severe or fatal, can occur with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, KEYTRUDA should be withheld or discontinued and corticosteroids administered if appropriate. For more information regarding immune-mediated adverse reactions, please read the additional Selected Safety Information below.

KEYNOTE-426
First-line Treatment of Advanced RCC in Combination With Axitinib

The efficacy of KEYTRUDA in combination with axitinib was investigated in KEYNOTE-426 (NCT02853331), a randomized, multicenter, open-label trial conducted in 861 patients who had not received systemic therapy for advanced RCC. Patients were enrolled regardless of PD-L1 tumor expression status. Patients with active autoimmune disease requiring systemic immunosuppression within the last 2 years were ineligible. Randomization was stratified by International Metastatic RCC Database Consortium (IMDC) risk categories (favorable versus intermediate versus poor) and geographic region (North America versus Western Europe versus “Rest of the World”).

Patients were randomized (1:1) to one of the following treatment arms:

KEYTRUDA 200 mg intravenously every 3 weeks up to 24 months in combination with axitinib 5 mg orally, twice daily. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive cycles (6 weeks) could increase to 7 mg and then subsequently to 10 mg twice daily. Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity.
Sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks.

Treatment with KEYTRUDA and axitinib continued until Response Evaluation Criteria in Solid Tumors (RECIST) v1.1-defined progression of disease or unacceptable toxicity. Administration of KEYTRUDA and axitinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessment of tumor status was performed at baseline, after randomization at Week 12, then every 6 weeks thereafter until Week 54, and then every 12 weeks thereafter.

The study population characteristics were: median age of 62 years (range: 26 to 90); 38% age 65 or older; 73% male; 79% White and 16% Asian; 19% and 80% of patients had a baseline Karnofsky Performance Scale (KPS) of 70 to 80 and 90 to 100, respectively; and patient distribution by IMDC risk categories was 31% favorable, 56% intermediate and 13% poor.

The main efficacy outcome measures were overall survival (OS) and progression-free survival (PFS) as assessed by blinded independent central review (BICR) according to modified RECIST v1.1. Additional efficacy outcome measures included overall response rate (ORR), as assessed by BICR. A statistically significant improvement in OS was demonstrated at the pre-specified interim analysis in patients randomized to KEYTRUDA in combination with axitinib compared with sunitinib. The trial also demonstrated statistically significant improvement in PFS and ORR. The table below summarizes the efficacy results for KEYNOTE-426. The median follow-up time was 12.8 months (range 0.1 to 22.0 months). Consistent results were observed across pre-specified subgroups, IMDC risk categories and PD-L1 tumor expression status.

Efficacy Results in KEYNOTE-426

Endpoint

KEYTRUDA
with axitinib
n=432

Sunitinib
n=429

OS

Number of patients with event (%)

59 (14%)

97 (23%)

Median in months (95% CI)

NR (NR, NR)

NR (NR, NR)

Hazard ratio* (95% CI)

0.53 (0.38, 0.74)

p-Value†

<0.0001‡

12-month OS rate

90% (86, 92)

78% (74, 82)

PFS

 

Number of patients with event (%)

183 (42%)

212 (49%)

Median in months (95% CI)

15.1 (12.6, 17.7)

11.1 (8.7, 12.5)

Hazard ratio* (95% CI)

0.69 (0.57, 0.84)

p-Value†

0.0001§

ORR

Overall confirmed response rate
(95% CI)

59% (54, 64)

36% (31, 40)

Complete response

6%

2%

Partial response

53%

34%

p-Value¶

<0.0001

*Based on the stratified Cox proportional hazard model

†Based on stratified log-rank test

‡p-Value (one-sided) is compared with the allocated alpha of 0.0001 for this interim analysis (with 39% of the planned number of events for final analysis).

§p-Value (one-sided) is compared with the allocated alpha of 0.0013 for this interim analysis (with 81% of the planned number of events for final analysis).

¶Based on Miettinen and Nurminen method stratified by IMDC risk group and geographic region

NR=not reached

CI=confidence interval.

Recommended Dosage for RCC

The recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months in patients without disease progression. When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. See also the Prescribing Information for recommended axitinib dosing information.

Selected Safety Information for KEYTRUDA® (pembrolizumab) injection 100 mg (continued)

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%), and occurred more frequently in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). 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 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). 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.

Immune-Mediated Hepatitis, or Hepatotoxicity (in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). 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.

Hepatotoxicity (in Combination With Axitinib)

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevations compared to KEYTRUDA alone. Grades 3 and 4 increased ALT and AST were seen in 20% and 13% of patients, respectively. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are used in monotherapy. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.
Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency), thyroid function (prior to and periodically during treatment), and hyperglycemia. For hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 and withhold or discontinue for Grade 3 or 4 hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. 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 to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.
Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.
In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a programmed death receptor-1 (PD-1) or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-426, when KEYTRUDA was administered in combination with axitinib, fatal adverse reactions occurred in 3.3% of 429 patients. Serious adverse reactions occurred in 40% of patients, the most frequent (≥1%) were hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction occurred in 31% of patients; KEYTRUDA only (13%), axitinib only (13%), and the combination (8%); the most common were hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

Lactation

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the final dose.

Before prescribing KEYTRUDA® (pembrolizumab), please read the Prescribing Information.
The Medication Guide also is available.

Corporate Member Merck - NEW Indication

KEYTRUDA (Pembrolizumab)
April, 2018

The U.S. Food and Drug Administration (FDA) has approved two new indications for KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, for certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. In the first-line setting, KEYTRUDA is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are ineligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In the second-line setting, KEYTRUDA is now approved for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. KEYTRUDA is approved for use in these indications at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Corporate Member Seattle Genetics - NEW Indication

ADCETRIS® (brentuximab vedotin)
April, 2018

New FDA-approved indication for ADCETRIS® (brentuximab vedotin) for adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL) in combination with chemotherapy.  This approval was based on the results of the Phase 3 ECHELON-1 trial,  a multi-center, randomized, open-label, global, superiority trial of A+AVD (ADCETRIS + doxorubicin, vinblastine, dacarbazine) vs ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in patients with newly diagnosed advanced-stage cHL. The ECHELON-1 trial enrolled 1,334 patients with Stage III or IV cHL and randomized patients 1:1 to receive up to 6 cycles of A+AVD or ABVD on Days 1 and 15 of each 28-day cycle.

Corporate Member Eli Lilly - NEW Approval

LARTRUVO (olaratumab)
April, 2018

LARTRUVO is indicated, in combination with doxorubicin, for the treatment of adult patients with soft tissue sarcoma (STS) with a histologic subtype for which an anthracycline-containing regimen is appropriate and which is not amenable to curative treatment with radiotherapy or surgery. 

Corporate Member Merck - EXPANDED INDICATION

KEYTRUDA (Pembrolizumab)
April, 2018

KEYTRUDA is indicated for the first-line treatment of patients with metastatic non–small cell lung cancer (mNSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

Corporate Member Merck - NEW Formulation

EMEND™ (fosaprepitant)
July, 2017

FDA approval for a new formulation of EMEND for injection that has a lower concentration of edetate disodium (EDTA), an inactive ingredient.  This new formulation (5.4 mg EDTA, NDC 0006-3061-00) will replace the existing formulation (18.8 mg EDTA, NDC 0006-3941-32).  The purpose of this formulation change is to support ongoing regulatory activities for EMEND.

Corporate Member AstraZeneca - NEW Indication

TAGRISSO (Osimertinib)
June, 2017

The US Food and Drug Administration (FDA) granted full approval for TAGRISSO® (osimertinib) 80mg once-daily tablets, for the treatment of patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer (NSCLC), as detected by an FDA-approved test, whose disease has progressed on or after an EGFR tyrosine kinase inhibitor (TKI) therapy. The full approval is based the randomized, Phase III AURA3 trial, where TAGRISSO significantly improved progression-free survival (PFS) versus platinum-based doublet chemotherapy, providing 10.1 months of median progression-free survival compared to 4.4 months from chemotherapy (hazard ratio 0.30; 70% risk reduction; 95% Confidence Interval [CI]: 0.23; 0.41; P<0.001). Additionally, TAGRISSO demonstrated efficacy in patients with measurable central nervous system (CNS) lesions at baseline. TAGRISSO was granted Fast Track, Breakthrough Therapy and Priority Review by the FDA, and received Accelerated Approval for this indication in 2015, based on tumor response rate and duration of response.

Corporate Member Merck - NEW Indication

KEYTRUDA (Pembrolizumab)
June, 2017

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. 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 the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Corporate Member Merck - NEW Indication

KEYTRUDA (Pembrolizumab)
June, 2017

Merck is pleased to announce that KEYTRUDA is now the only anti–PD-1 approved in combination with carbo/pem for the first line treatment of patients with nonsquamous metastatic NSCLC (mNSCLC) irrespective of PD-L1 expression. KEYTRUDA is also the only anti–PD-1 approved as first-line monotherapy for patients with nonsquamous and squamous mNSCLC whose tumors have high PD-L1 expression (TPS ≥50%) and are negative for EGFR and ALK genomic tumor aberrations.

Corporate Member AstraZeneca - NEW Approval

IMFINZI™ (durvalumab)
June, 2017

The US Food and Drug Administration (FDA) has granted accelerated approval to IMFINZI™ (durvalumab) for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy, or whose disease has progressed within 12 months of receiving platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery.

Corporate Member Takeda - NEW Indication

ALUNBRIG (brigatinib)
June, 2017

Takeda Oncology is proud to announce the FDA approval of ALUNBRIG (brigatinib), a kinase inhibitor indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Corporate Member Genentech - NEW Indication

TECENTRIQ (Atezolizumab)
April, 2017

TECENTRIQ for the treatment of people with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. TECENTRIQ was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery (neoadjuvant) or after surgery (adjuvant). It is not known if TECENTRIQ is safe and effective in children. Bladder cancer is the most common type of urothelial carcinoma, and up to half of all people with the advanced form of the disease are unable to receive cisplatin chemotherapy as an initial treatment and therefore have a high unmet medical need. Urothelial carcinoma also includes cancers of the urethra, ureters and renal pelvis. 

Corporate Member Celgene - NEW Indication

Revlimid (lenalidomide)
April, 2017

REVLIMID is indicated as maintenance therapy in patients with multiple myeloma (MM) following autologous hematopoietic stem cell transplantation (auto-HSCT). REVLIMID is not indicated and is not recommended for the treatment of patients with chronic lymphocytic leukemia (CLL) outside of controlled clinical trials.

Corporate Member EMD Serono - NEW Approval

BAVENCIO® (avelumab)
March, 2017

BAVENCIO is a programmed death ligand-1 (PD-L1) blocking antibody indicated for the treatment of adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (MCC).

Corporate Member Merck - NEW Indication

KEYTRUDA (Pembrolizumab)
March, 2017

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory cHL, or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response.

Corporate Member Genentech - NEW Approval

TECENTRIQ (Atezolizumab)
October, 2016

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.

Corporate Member Merck - Expanded Indication

EMEND (fosaprepitant dimeglumine)
August, 2016

EMEND® is a substance P/neurokinin 1 (NK1) receptor antagonist. EMEND for oral suspension is indicated in combination with other antiemetic agents, in patients 6 months of age and older for prevention of:

  • acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin (1.1)
  • nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy(MEC)

Corporate Member Merck - EXPANDED INDICATION

KEYTRUDA (Pembrolizumab)
August, 2016

For Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma with Disease Progression on or After Platinum-Containing Chemotherapy. 

 
 
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