FDA approved IMFINZI® (durvalumab) in combination with standard-of-care (SoC) chemotherapy (etoposide with either carboplatin or cisplatin) in the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC)

Approval Based on OS Data from Phase III CASPIAN Trial of IMFINZI

With this approval, IMFINZI becomes the only immunotherapy to demonstrate a significant overall survival benefit in combination with etoposide and either carboplatin or cisplatin in patients with extensive-stage (ES-SCLC). The FDA approval was based on the Phase III CASPIAN results, in which the risk of death was reduced by 27% (equal to a hazard ratio of 0.73), with median overall survival (OS) of 13.0 months (95% CI, 11.5-14.8) for IMFINZI plus chemotherapy vs 10.3 months (95% CI, 9.3-11.2) for SoC chemotherapy alone P=0.00471. Adverse reactions were similar with IMFINZI + EP and EP alone and consistent with the safety profiles for both IMFINZI and EP2.

The CASPIAN trial uses a fixed dose of IMFINZI (1500 mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks as a single agent until disease progression or acceptable toxicity.

As always, please don’t hesitate to contact me with any questions.

Click here for IMFINZI Prescribing Information and scroll down for Important Safety Information.

Select Safety Information

Serious, potentially fatal risks were seen with IMFINZI in the CASPIAN trial. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%) and COPD (1.1%).

Immune-mediated adverse reactions including immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies (including thyroid disorders, adrenal insufficiency, type 1 diabetes, and hypophysitis), nephritis, dermatologic reactions, other immune-mediated adverse reactions, infection, and infusion-related reactions were reported in patients receiving IMFINZI in the CASPIAN trial.

The most common adverse reactions (≥20%) were nausea, fatigue/asthenia and alopecia.

Advise women not to become pregnant or breastfeed during treatment with IMFINZI and for at least 3 months after the last dose.

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Please refer to the Important Safety Information included below and the full Prescribing Information for important dosage modification and management information specific to adverse reactions.

Important Safety Information

There are no contraindications for IMFINZI® (durvalumab).

IMFINZI can cause serious, potentially fatal adverse reactions including immune-mediated pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, dermatologic reactions, other immune-mediated adverse reactions, infection, and infusion-related reactions. Please refer to the full Prescribing Information for important dosage modification and management information specific to adverse reactions.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of pneumonitis and evaluate with radiographic imaging when suspected. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold IMFINZI for Grade 2 pneumonitis; permanently discontinue for Grade 3 or 4 pneumonitis.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, pneumonitis occurred in 5% of patients, including Grade 3 (0.8%), Grade 4 (<0.1%), and Grade 5 (0.3%) pneumonitis. Pneumonitis led to discontinuation of IMFINZI in 1.5% of the 1889 patients. The incidence of pneumonitis (including radiation pneumonitis) was higher in patients in the PACIFIC study who completed treatment with definitive chemoradiation within 42 days prior to initiation of IMFINZI (34%) compared to patients in other clinical studies (2.3%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In the PACIFIC study, the incidence of Grade 3 pneumonitis was 3.4% and of Grade 5 pneumonitis was 1.1% in the IMFINZI arm. In the PACIFIC study, pneumonitis led to discontinuation of IMFINZI in 6% of patients.

The frequency and severity of immune-mediated pneumonitis were similar whether IMFINZI was given as a single agent in patients with various cancers or in combination with chemotherapy in patients with ES-SCLC.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis, defined as requiring use of corticosteroids. Fatal cases have been reported. Monitor patients for signs and symptoms of hepatitis during and after discontinuation of IMFINZI, including clinical chemistry monitoring. Administer corticosteroids for Grade 2 or higher elevations of ALT, AST, and/or total bilirubin. Withhold IMFINZI for ALT or AST greater than 3 but less than or equal to 8 times the ULN or total bilirubin greater than 1.5 but less than or equal to 5 times the ULN; permanently discontinue IMFINZI for ALT or AST greater than 8 times the ULN or total bilirubin greater than 5 times the ULN or concurrent ALT or AST greater than 3 times the ULN and total bilirubin greater than 2 times the ULN with no other cause.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hepatitis occurred in 12% of patients, including Grade 3 (4.4%), Grade 4 (0.4%), and Grade 5 (0.2%) hepatitis. Hepatitis led to discontinuation of IMFINZI in 0.7% of the 1889 patients.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis, defined as requiring use of corticosteroids. Administer corticosteroids for Grade 2 or greater colitis or diarrhea. Withhold IMFINZI for Grade 2 colitis or diarrhea; permanently discontinue for Grade 3 or 4 colitis or diarrhea.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, colitis or diarrhea occurred in 18% of patients, including Grade 3 (1.0%) and Grade 4 (0.1%) immune-mediated colitis. Diarrhea or colitis led to discontinuation of IMFINZI in 0.4% of the 1889 patients.

Immune-Mediated Endocrinopathies

IMFINZI can cause immune-mediated endocrinopathies, including thyroid disorders, adrenal insufficiency, type 1 diabetes mellitus, and hypophysitis/hypopituitarism. Monitor patients for clinical signs and symptoms of endocrinopathies.

Thyroid disorders—Monitor thyroid function prior to and periodically during treatment. Initiate hormone replacement therapy or medical management of hyperthyroidism as clinically indicated. Withhold IMFINZI for Grades 2–4 hyperthyroidism, until clinically stable. Continue IMFINZI for hypothyroidism.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, hypothyroidism occurred in 11% of patients, while hyperthyroidism occurred in 7% of patients. Thyroiditis occurred in 0.9% of patients, including Grade 3 (<0.1%) thyroiditis. Hypothyroidism was preceded by thyroiditis or hyperthyroidism in 25% of patients.

· Adrenal insufficiency—Administer corticosteroids as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher adrenal insufficiency. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, adrenal insufficiency occurred in 0.7% of patients, including Grade 3 (<0.1%) adrenal insufficiency.

· Type 1 diabetes mellitus—Initiate treatment with insulin as clinically indicated. Withhold IMFINZI for Grades 2–4 type 1 diabetes mellitus, until clinically stable. In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, type 1 diabetes mellitus occurred in <0.1% of patients.

· Hypophysitis—Administer corticosteroids and hormone replacement as clinically indicated and withhold IMFINZI until clinically stable for Grade 2 or higher hypophysitis. Hypopituitarism leading to adrenal insufficiency and diabetes insipidus occurred in <0.1% of 1889 patients with various cancers who received IMFINZI.

Immune-Mediated Nephritis

IMFINZI can cause immune-mediated nephritis, defined as evidence of renal dysfunction requiring use of corticosteroids. Fatal cases have occurred. Monitor patients for abnormal renal function tests prior to and periodically during treatment with IMFINZI. Administer corticosteroids as clinically indicated. Withhold IMFINZI for creatinine greater than 1.5 to 3 times the ULN; permanently discontinue IMFINZI and administer corticosteroids in patients with creatinine greater than 3 times the ULN.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, nephritis (reported as any of the following: increased creatinine or urea, acute kidney injury, renal failure, decreased glomerular filtration rate, tubulointerstitial nephritis, decreased creatinine clearance, glomerulonephritis, and nephritis) occurred in 6.3% of the patients including Grade 3 (1.1%), Grade 4 (0.2%), and Grade 5 (0.1%) nephritis. IMFINZI was discontinued in 0.3% of the 1889 patients.

Immune-Mediated Dermatologic Reactions

IMFINZI can cause immune-mediated rash. Stevens Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) has occurred with other products in this class. Administer corticosteroids for Grade 2 rash or dermatitis lasting for more than 1 week or for Grade 3 or 4 rash or dermatitis. Withhold IMFINZI for Grade 2 rash or dermatitis lasting longer than 1 week or Grade 3 rash or dermatitis; permanently discontinue IMFINZI in patients with Grade 4 rash or dermatitis.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, 26% of patients developed rash or dermatitis and 0.4% of the patients developed vitiligo. Rash or dermatitis led to discontinuation of IMFINZI in 0.1% of the 1889 patients.

Other Immune-Mediated Adverse Reactions

IMFINZI can cause severe and fatal immune-mediated adverse reactions. These immune-mediated reactions may involve any organ system. While immune-mediated reactions usually manifest during treatment with IMFINZI, immune-mediated adverse reactions can also manifest after discontinuation of IMFINZI. For suspected immune-mediated adverse reactions, exclude other causes and initiate corticosteroids as clinically indicated. Withhold IMFINZI for Grade 3 immune-mediated adverse reactions, unless clinical judgment indicates discontinuation; permanently discontinue IMFINZI for Grade 4 adverse reactions.

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1889 patients who received IMFINZI: aseptic meningitis, hemolytic anemia, immune thrombocytopenic purpura, myocarditis, myositis, and ocular inflammatory toxicity, including uveitis and keratitis. Additional clinically significant immune-mediated adverse reactions have been seen with other products in this class (see Warnings and Precautions Section 5.7 of IMFINZI full Prescribing Information).

Infection

IMFINZI can cause serious infections, including fatal cases. Monitor patients for signs and symptoms of infection and treat as clinically indicated. Withhold IMFINZI for Grade 3 or 4 infection, until clinically stable.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infections occurred in 43% of patients, including Grade 3 (8%), Grade 4 (1.9%), and Grade 5 (1.0%). The overall incidence of infections in IMFINZI-treated patients in the PACIFIC study (56%) was higher compared to patients in other clinical studies (38%) in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI. In patients with UC in Study 1108 (n=182), the most common Grade 3 or higher infection was urinary tract infections, which occurred in 4% of patients. In patients with Stage III NSCLC in the PACIFIC study, the most common Grade 3 or higher infection was pneumonia, which occurred in 5% of patients.

Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor patients for signs and symptoms of an infusion-related reaction. Interrupt or slow the rate of infusion for Grades 1–2 infusion-related reactions; permanently discontinue for Grades 3–4 infusion-related reactions.

In clinical studies enrolling 1889 patients with various cancers who received IMFINZI, infusion-related reactions occurred in 2.2% of patients, including Grade 3 (0.3%).

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. There are no data on the use of IMFINZI in pregnant women. Advise pregnant women of the potential risk to a fetus and advise women of reproductive potential to use effective contraception during treatment and for at least 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for at least 3 months after the last dose.

Most Common Adverse Reactions

· In patients with extensive-stage SCLC in the CASPIAN study (n=265), the most common adverse reactions (≥20%) were nausea, fatigue/asthenia, and alopecia. The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%)

· In patients with extensive-stage SCLC in the CASPIAN study (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy

The safety and effectiveness of IMFINZI have not been established in pediatric patients.

Indication

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

References:

IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2020.

Paz-Ares L, Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.

US-35716 Last Updated 3/20

Video Platform for COVID-19 Patient Communications is now available, sponsored by AstraZeneca.

Video Platform for COVID-19 Patient Communications is now available, sponsored by AstraZeneca.

 

In an effort to support healthcare professionals during this unprecedented time and provide an efficient way, to address the overwhelming influx of calls and emails from patients with questions and concerns about COVID-19, AstraZeneca is sponsoring a healthcare technology company called Vidscrip, through June 30, 2020, or until such time as the COVID-19 virus is no longer a US public health emergency.

 

This program enables healthcare professionals to use their own computer to record short videos that answer questions to common COVID-19 questions and then share those videos with their patients through their web page, or through direct links to their patient’s phone via a personalized email or text message. 

 

For more information visit www.vidscrip.com/COVID19 or text “COVIDAZUS” to 73771.

Regence to Expand Telemedicine Coverage

FROM REGENCE INSURANCE:

  • Given the extraordinary challenges our medical community is facing, we are expanding the ability for our providers to provide telemedicine services when appropriate for their patients at the same reimbursement as if in the office.  

    This temporary expansion is for both medical and behavioral health telehealth services to our Individual, group (including administrative services only groups who have the telehealth benefit), and Medicare members. This expansion will remain in effect through each state’s emergency declaration. 

     Details are on our provider webpage and highlighted below:

    Telehealth expansion:

    •We are expanding the services that can be offered by in-network providers via telehealth. 

    •The visits are considered the same as in-person visits and are paid consistently with in-person visits. 

    •The member’s coinsurance and deductible will apply to these services. 

    •We are following the U.S. Department of Health and Human Services’ (HHS’) lead on discretion with respect to HIPAA compliant platform requirements. 

    The services must: 

    ◦Be safely and effectively delivered via telehealth 

    ◦Meet the code definition that is billed when provided via telehealth 

    ◦Meet existing coverage criteria, including pre-authorization requirements and medical necessity 

      •Under this expansion for claims to process correctly, claims must be submitted with POS 11 or IOP and the GT modifier. (Note: To receive reimbursement consistent with an in-office visit, the POS must be either 11 or IOP. The GT modifier will indicate that the services were rendered via telehealth.) 

      •Claims can be submitted on or after Tuesday, March 24, 2020, for dates of service beginning on March 19, 2020. 

    Additionally, we will continue to cover the medical and behavioral health codes, as outlined in our Virtual Care (Administrative #132) reimbursement policy. Claims submitted following the guidelines in this policy will be paid as they have been.

    Thank you all for the amazing work you do every day.


    Drew Oliveira, MD, MHA
    Senior Executive Medical Director, Regence Blue Shield

Merck is pleased to announce that KEYTRUDA® (pembrolizumab) has been approved for...

Merck is pleased to announce that KEYTRUDA® (pembrolizumab) has been approved by the FDA for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

·    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 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.

HSCT=hematopoietic stem cell transplantation.

KEYNOTE-057

The efficacy of KEYTRUDA was investigated in KEYNOTE-057 (NCT02625961), a multicenter, open-label, single-arm trial in 96 patients with BCG-unresponsive, high-risk, NMIBC with CIS with or without papillary tumors who were ineligible for or had elected not to undergo cystectomy. BCG-unresponsive high-risk NMIBC was defined as persistent disease despite adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. Adequate BCG therapy was defined as administration of at least 5 of 6 doses of an initial induction course plus either of: at least 2 of 3 doses of maintenance therapy or at least 2 of 6 doses of a second induction course. Prior to treatment, all patients had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components). Residual CIS (Tis components) not amenable to complete resection was allowed. The trial excluded patients with muscle invasive (ie, T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma, concurrent extravesical (ie, urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, or autoimmune disease or a medical condition that required immunosuppression.

Patients received KEYTRUDA 200 mg every 3 weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC, or progressive disease. Assessment of tumor status was performed every 12 weeks for 2 years and then every 24 weeks for 3 years, and patients without disease progression could be treated for up to 24 months. The major efficacy outcome measures were complete response (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable], urine cytology, and computed tomography urography [CTU] imaging) and duration of response.

The study population characteristics were: median age of 73 years (range: 44–92 years); 44% age ≥75; 84% male; 67% White; and 73% and 27% with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, respectively. Tumor pattern at study entry was CIS with T1 (13%), CIS with high grade TA (25%), and CIS (63%). Baseline high-risk NMIBC disease status was 27% persistent and 73% recurrent. The median number of prior instillations of BCG was 12.

The median follow-up time was 28.0 months (range: 4.6–40.5 months). Efficacy results are summarized below.

Efficacy Results in KEYNOTE-057

Endpoint

KEYTRUDA
200 mg every 3 weeks
n=96

Complete Response Rate (95% CI)

41% (31, 51)

Duration of Response*

 

Median in months (range)

16.2 (0.0+, 30.4+)

% (n) with duration ≥12 months

46% (18)

*Based on patients (n=39) that achieved a complete response; reflects period from the time complete response was
_achieved

+Denotes ongoing

Recommended Dosage for NMIBC

The recommended dose of KEYTRUDA in patients with high-risk BCG-unresponsive NMIBC is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

SELECTED SAFETY INFORMATION (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

·    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 adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). 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 adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or 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 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-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those ≥2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).

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.

PD-1=programmed death receptor-1.

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

Approval of PADCEV™ (enfortumab vedotin‑ejfv) by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC)

We are excited to announce the approval of PADCEV™ (enfortumab vedotin‑ejfv) by the U.S. Food and Drug

Administration (FDA) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC)

who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor,

and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.

This indication is approved under accelerated approval based on tumor response rate. Continued approval may be

contingent upon verification and description of clinical benefit in confirmatory trials.

PADCEV is now the first treatment option FDA approved for adult patients in this post platinum, post PD-1/L1

inhibitor setting.

Important Safety Information

Warnings and Precautions

Hyperglycemia occurred in patients treated with PADCEV, including death and diabetic ketoacidosis (DKA), in those

with and without pre-existing diabetes mellitus. The incidence of Grade 3-4 hyperglycemia increased consistently

in patients with higher body mass index and in patients with higher baseline A1C. In one clinical trial, 8% of patients

developed Grade 3-4 hyperglycemia. Patients with baseline hemoglobin A1C ≥8% were excluded. Closely monitor

blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated

(>250 mg/dL), withhold PADCEV.

Peripheral neuropathy (PN), predominantly sensory, occurred in 49% of the 310 patients treated with PADCEV in

clinical trials; 2% experienced Grade 3 reactions. In one clinical trial, peripheral neuropathy occurred in patients treated

with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 was 3.8 months

(range: 0.6 to 9.2). Neuropathy led to treatment discontinuation in 6% of patients. At the time of their last evaluation,

19% had complete resolution, and 26% had partial improvement. Monitor patients for symptoms of new or worsening

peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy

occurs. Permanently discontinue PADCEV in patients that develop Grade ≥3 peripheral neuropathy.

Ocular disorders occurred in 46% of the 310 patients treated with PADCEV. The majority of these events involved

the cornea and included keratitis, blurred vision, limbal stem cell deficiency and other events associated with dry eyes.

Dry eye symptoms occurred in 36% of patients, and blurred vision occurred in 14% of patients, during treatment

with PADCEV. The median time to onset to symptomatic ocular disorder was 1.9 months (range: 0.3 to 6.2). Monitor

patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular

symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic

exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Please see additional Important Safety Information on the next page and click here for Full Prescribing Information.

Daiichi Sankyo and AstraZeneca

Daiichi Sankyo and AstraZeneca announced that the US Food and Drug Administration (FDA) approved ENHERTU® (fam-trastuzumab deruxtecan-nxki) for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. 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.

For more information, please visit ENHERTUhcp.com

New St. Gallen International Breast Cancer Guidelines Recommend Oncotype DX Breast Recurrence Score® Test to Guide Chemotherapy for Node-negative and Node-positive Early-stage Breast Cancer

New St. Gallen International Breast Cancer Guidelines Recommend Oncotype DX Breast Recurrence Score® Test to Guide Chemotherapy for Node-negative and Node-positive Early-stage Breast Cancer

- Guidelines include TAILORx-defined cutoff of 26 for determining chemotherapy benefit in node-negative disease, and recommend that more women with limited nodal involvement may avoid chemotherapy

- Oncotype DX® test recommended based on prospective landmark TAILORx and German PlanB studies, recognized as key scientific and clinical research innovations of the past two years

- Genomic testing strongly endorsed by vast majority of panelists

REDWOOD CITY, Calif., Aug. 21, 2019  Genomic Health today announced that, based on results from the prospective TAILORx1 and PlanB2 studies, the 16thSt. Gallen International Breast Cancer Conference Expert Panel has recommended the Oncotype DX Breast Recurrence Score® test to guide chemotherapy treatment use for patients with hormone-receptor positive, HER-2 negative early-stage breast cancer with and without lymph node involvement (up to three positive nodes).

In particular, the panelists recognized the value of the landmark TAILORx study results and noted that women with node-negative cancers and Recurrence Score® results ≤25 do not need chemotherapy.3 This group represents up to about 80% of patients who may be safely spared chemotherapy. The Breast Recurrence Score test also identifies those patients (with results of 26 to 100) who may receive a life-saving benefit from chemotherapy.

In the new guidelines, genomic testing with robust validation through prospective, randomized trials is preferred over clinical-pathological features "for basing the critical yes/no chemotherapy decision." 4 Results from a recently published subset analysis of the prospective, randomized TAILORx study5 showed that only the Breast Recurrence Score test is predictive of chemotherapy benefit; clinical and pathological features are only prognostic and do not provide predictive information.