Exelixis is pleased to announce the FDA approval of its first combination therapy–CABOMETYX + OPDIVO–for the first-line treatment of patients with advanced renal cell carcinoma (aRCC).1

This new approval in aRCC is supported by clinical data from the CheckMate-9ER trial. The major efficacy outcome measure was PFS.* Additional efficacy outcome measures were OS and ORR.* Based on the results of CheckMate-9ER, CABOMETYX + OPDIVO is the first and only 1L aRCC combination treatment to double PFS and ORR while delivering superior OS.1 Please see the data of CABOMETYX + OPDIVO vs sunitinib below.

*PFS and ORR were assessed by BICR.1
1L=first-line; BICR=blinded independent central review; ORR=objective response rate;
OS=overall survival; PFS=progression-free survival.

INDICATIONS

CABOMETYX® (cabozantinib), in combination with nivolumab, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (aRCC).

CABOMETYX is indicated for the treatment of patients with aRCC.

SELECT IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage: Severe and fatal hemorrhages occurred with CABOMETYX. The incidence of Grade 3 to 5 hemorrhagic events was 5% in CABOMETYX patients in RCC and HCC studies. Discontinue CABOMETYX for Grade 3 or 4 hemorrhage. Do not administer CABOMETYX to patients who have a recent history of hemorrhage, including hemoptysis, hematemesis, or melena.

Please see additional Important Safety Information for CABOMETYX below and full Prescribing Information by clicking here.

 

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Written by: Brandy Persson, PharmD, BCPS, BCOP and Rebecca Fanning, PharmD, BCPS, Cone Health

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Positive Quality Intervention: Fam-trastuzumab deruxtecan-nxki (Enhertu®) management

Description: Fam-trastuzumab deruxtecan-nxki is indicated for the treatment of:

  • adult patients with unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer previously treated with two or more anti-HER2-based regimens1,2. This indication is under accelerated approval based on tumor response and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
  • adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen1,6

The purpose of this PQI is to provide guidance for management of fam-trastuzumab deruxtecan-nxki.

Background:  Fam-trastuzumab deruxtecan-nxki is a HER2 directed antibody-drug conjugate (ADC). Fam-trastuzumab deruxtecan-nxki was FDA approved for metastatic breast cancer in December 2019 based on results from the DESTINY-Breast01 trial that established its efficacy and safety in patients previously treated with trastuzumab emtansine. The overall response (complete response and partial response) was 60.9%. Secondary endpoints included a median progression free survival of 16.4 months in all patients and 18.1 months in 24 patients enrolled with asymptomatic brain metastases.2 Fam-trastuzumab deruxtecan-nxki was FDA approved in January 2021 for patients with gastric and gastroesophageal junction adenocarcinoma based on the results of the DESTINY-Gastric01 trial.   This study evaluated the safety and efficacy versus physician’s choice chemotherapy (irinotecan or paclitaxel monotherapy) in patients who had progressed on at least two prior regimens which included trastuzumab, a fluoropyrimidine and a platinum agent.  The study demonstrated a statistically significant improvement in the major efficacy outcomes of median overall survival (12.5 vs 8.4 mo) and confirmed objective response rate (40.5% vs 11.3%).  Additional efficacy outcomes of median progression free survival (5.6 vs 3.5 mo) and median duration of response (11.3 vs 3.9 mo) were also improved.6

PQI Process:

  • Review the medical record
    • Ensure patient is an appropriate candidate for fam-trastuzumab deruxtecan-nxki (review indications)
    • Confirm patient does not have a history of Interstitial Lung Disease (ILD) and/or pneumonitis
      • Patients with this history were excluded from the DESTINY-Breast01 and DESTINY-Gastric01 studies. Although not a contraindication, ILD/pneumonitis is a boxed warning
    • Assess Left Ventricular Ejection Fraction (LVEF) prior to initiation
  • Patients with LVEF < 50% were not studied2,6
    • Evaluate CBC prior to initiation, as well as prior to each dose, and as clinically indicated
  • Review treatment plan
    • Verify premedication orders:
      • Antiemetics – Moderately emetogenic3– 5-HT3 antagonist + dexamethasone prior to treatment and consideration for days 2 and 3; PRN antiemetic available for home use

PQI Process continued:

  • Acetaminophen + H1 blocker may be included to prevent infusion related reactions per institutional policy or provider preference
  • Verify dosing of fam-trastuzumab deruxtecan-nxki1
    • Breast cancer dosing is 5.4 mg/kg intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity
    • Gastric cancer dosing is 6.4 mg/kg intravenous infusion every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity
    • First infusion is administered over 90 minutes
    • If patient tolerates the first infusion, subsequent infusions may be given over 30 minutes
      • Slow or interrupt infusion rate if patient develops infusion-related symptoms
    • No dose adjustments required for mild or moderate renal or hepatic impairment
    • Patients with severe renal or hepatic impairment were not studied
  • Monitoring1
    • CBC: baseline, then before each treatment cycle
      • Fam-trastuzumab deruxtecan-nxki treatment should be interrupted for patients with a neutrophil count < 1,000 cells/mm3 or a platelet count < 50,000/microliter
      • Growth factor support may be used to maintain counts when appropriate2,5,6
    • LVEF: baseline and at regular intervals during treatment as clinically indicated
      • Discontinue treatment if LVEF < 40%, if an absolute LVEF decrease of > 20% from baseline LVEF or symptomatic congestive heart failure
    • Interstitial lung disease (ILD) and pneumonitis: Monitor and promptly investigate signs and symptoms including cough, dyspnea, fever, and new or worsening respiratory symptoms.
      • Permanently discontinue in all patients with grade 2 or higher ILD/ pneumonitis, promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent). Continue upon improvement for at least 14 days followed by gradual taper (e.g.,for at least 4 weeks)
    • See package insert for additional dose modifications and management information
    • Evaluate the need for dose modifications. Do not re-escalate dose after dose reduction is made
      • Dose modifications for breast cancer:
        • First dose reduction: 4.4 mg/kg
        • Second dose reduction: 3.2 mg/kg
        • Further required dose reductions: Discontinue treatment
      • Dose modifications for gastric cancer:
        • First dose reduction: 5.4 mg/kg
        • Second dose reduction: 4.4 mg/kg
        • Further required dose reductions: Discontinue treatment

 

PQI Process continued:

  • Preparation1
    • Reconstitute fam-trastuzumab deruxtecan-nxki 100 mg vials with 5 mL of Sterile Water for Injection, USP for a final concentration of 20 mg/mL
    • Inject dose into a 100 mL bag of 5% Dextrose Injection, USP. Do not use sodium chloride
    • Fam-trastuzumab deruxtecan-nxki is compatible with an infusion bag made of polyvinylchloride, or polyolefin (copolymer of ethylene and polypropylene)
  • Administration1
    • IV over 30 – 90 minutes with an infusion set made of polyolefin or polybutadiene and a 0.2- or 0.22-micron in-line polyethersulfone or polysulfone filter
    • 5% dextrose is recommended for priming and flushing the administrative line
    • Cover the infusion bag to protect from light

Patient Centered Activities:

  • Patient Education1,5
    • Instruct patient to report any new or worsening shortness of breath, dry cough, wheezing, or fever
    • Caution patient regarding a decreased white blood cell count (the cells that fight infections)
    • Review the possibility this drug could weaken the pumping action of the heart muscle. Promptly report any chest pain or tightness, rapid weight gain, significant swelling in ankles or trouble breathing. Your physician will test your heart before starting treatment and during treatment to monitor
    • Remind patient that this drug may cause significant hair loss
    • Instruct patient to report adverse events including fever, diarrhea, nausea/vomiting or fatigue
    • Ensure patient has access to supportive medications
      • Anti-nausea: (5-HT3 receptor antagonist, metoclopramide, or prochlorperazine)
      • Anti-diarrheal: Loperamide
    • Provide written medication information to patient

Supplemental Information:

  • Patient assistance: ENHERTU4U4
    • Patient Savings Program: Assists eligible commercial patients with their out-of-pocket costs
    • Patient Assistance Program: Assists qualifying uninsured, underinsured or Medicare patients who are having difficulty affording their medications
  • Assistance may also be available through independent charitable patient assistance foundations

References:

  1. Enhertu (fam-trastuzumab deruxtecan-nxki) [prescribing information]. Basking Ridge, NJ: Daiichi Sankyo, Inc.; January 2021.
  1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med 2020;382(7):610-621.
  2. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. Antiemesis. Version 2.2020. April 23, 2020.  Accessed October 12, 2020.
  3. ENHERTU4U: Patent Access to Treatment. https://www.enhertu4u.com/patient/affording-your-medicine.html.
  4. Fam-trastuzumab Derutecan-nxki (EnhertuÒ).  JNCCN Spotlights:  https://jnccn360.org/breast/jnccn-spotlights/fam-trastuzumab-deruxtecan-nxki.  Accessed October 16, 2020.
  5. Shitara K, Bang YJ, Iwasa S, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382:2419-2430.

Important notice: National Community Oncology Dispensing Association, Inc. (NCODA), has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional.  This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented.  NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.

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Written by: Tammy McClellan, PharmD, Riverside Healthcare

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Positive Quality Intervention: Patient Screening for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Description:

            The purpose of this PQI is to assess the individualized characteristics of the Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) patient and important screening measures in order to achieve optimal pharmacological therapy.

Background:

CLL/SLL, a type of non-Hodgkin Lymphoma, is an indolent cancer in which immature lymphocytes (primarily B lymphocytes) are found in the blood and bone marrow and/or in the lymph nodes. CLL and SLL are the same disease, but in CLL cancer cells are found mostly in the blood and bone marrow6. In SLL cancer cells are found mostly in the lymph nodes1. CLL/SLL has been described as a disease of defective mechanisms of apoptosis and not hyper-proliferation. CLL/SLL is considered both a lymphoma and leukemia. There are multiple screening tests (ex. FISH, IgVH, TP53) that will help provide insight to an informed course of action. Predictive testing is important to provide an informed decision regarding therapy selection within CLL/SLL. When pharmacological therapy is warranted, the healthcare professional can now proceed in making a selection of the most appropriate therapies. In addition, testing for minimal residual disease (MRD) can additionally be utilized to determine depth of response along with detection of disease relapse.7

PQI Process:

General Screening Guide (Visit cllsociety.org for more in-depth information)6

  • Review B-lymphocyte count at ≥5000 monoclonal (genetically identical) B-lymphocytes in the blood for the duration of at least three months. Confirm utilizing flow cytometry.
  • For SLL confirm documented location of enlarged lymph nodes and/or an enlarged spleen with less than 5000 B-lymphocytes in the blood. Confirmed with lymph node biopsy.
  • Secondary Symptoms
    • Weight loss >10% of body weight in previous 6 months
    • Severe fatigue (ambulatory and capable of all self-care but unable to carry out any work activities
    • Fevers >38°C for at least 2 weeks without evidence of infection
    • Drenching night sweats for more than a month without evidence of infection

Tests to confirm to discuss with care team to determine course of action after screening5:

  • FISH (Interphase fluorescence in situ hybridization) test for genetic abnormalities
    • Test before every treatment
    • An abnormality such as deletion 17p can affect response to chemotherapy
  • IgVH mutation status.
    • Test mutation status before the 1st treatment
    • Patients with a “mutated” IgVH immunoglobulin will respond with FCR based therapies
  • TP53 genetic testing
    • Test before every treatment
    • A TP53 mutation can affect response to chemotherapy

Additional MRD Testing as needed:

  • Polymerase Chain Reaction laboratory test (PCR)
  • Flow Cytometry
  • Next Generation Sequencing

Patient Considerations:

  • Patient’s age (64 years old or younger & 65 years old or older)
  • Presence of Comorbidities/Performance Status
  • Genetic abnormalities to review4:
    • Deletion 17p
    • Deletion 13q
    • Deletion 11q
    • TP53 mutation
    • Complex karyotype
  • Tumor burden/Risk for Tumor Lysis syndrome: Clinical and Laboratory assessments3:
    • Review physical exam notes: presence of “bulky disease”
    • Laboratory values to review: increased potassium, uric acid, phosphorous, LDH, and decreased calcium
    • Clinical abnormalities to note: renal disease/failure, arrhythmias, seizures, muscle cramps and weakness
    • Drug selection examples: allopurinol, febuxostat, rasburicase; monitor serum creatinine and electrolytes)
    • Note to provide rigorous hydration

Prophylactic measures2:

  • Cytomegalovirus (CMV) by Polymerase Chain Reaction (PCR): Consider use of ganciclovir (note: patients at higher risk are those receiving idelalisib, alemtuzumab, fludarabine-based chemotherapy and some small-molecule inhibitors)
  • Herpes virus: Consider providing acyclovir or equivalent
  • Pneumocytis Jiroveci Pneumonia (PJP): Review usage of sulfamethoxazole and trimethoprim or equivalent
  • Hepatitis B virus (HBV): Hepatitis B surface antigen and Hepatitis B core antibody testing by PCR

Patient Centered Activities:

  • Note complications of Monoclonal Antibody Therapy: mucocutaneous reactions, Stevens-Johnson Syndrome, etc.
  • CLL/SLL patients are at higher risk for developing non-melanomatous skin cancer (annual dermatologic skin screening is recommended in addition to other screenings)
  • Irradiate all blood products to avoid transfusion-associated graft-versus-host disease (GVHD)
  • Counsel patient on disease state, treatment regimen, what to expect, upcoming appointments/toxicology checks and adherence.

References:

  1. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms. Assessed at: https://www.cancer.gov/publications/dictionaries/cancer-terms/search?contains=false&q=cll. 6-12-2020
  2. National Comprehensive Cancer Network (NCCN). NCCN Guidelines Version 4.2020-Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Accessed at: https://www.nccn.org/professionals/physician_gls/pdf/cll.pdf.
  3. Gupta, Arjun MD & Moore, Joseph A. MD. Tumor Lysis Syndrome [published online May 10, 2018]. JAMA Oncology. Doi:10.1001/jamaoncol.2018.0613. Accessed at: https://jamanetwork.com/journals/jamaoncology/fullarticle/2680750.
  4. National Institutes of Health (NIH): National Library of Medicine. Cytogenetic Abnormalities in Chronic Lymphocytic Leukemia. Accessed at: https://pubmed.ncbi.nlm.nih.gov/11347338/.
  5. CLL Society. Test Before Treat. Accessed at: https://cllsociety.org/cll-101/test-before-treat/.
  6. CLL Society. Diagnosis of Chronic Lymphocytic Leukemia. Accessed at: https://cllsociety.org/cll-101/test-before-treat/.
  7. CLL Society. Minimal Residual Disease Testing 101: Definitions to Know. Accessed at: https://cllsociety.org/2020/09/mrd-glossary/.
Important notice: National Community Oncology Dispensing Association, Inc. (NCODA), has developed this Positive Quality Intervention platform. This platform represents a brief summary of medication uses and therapy options derived from information provided by the drug manufacturer and other resources. This platform is intended as an educational aid and does not provide individual medical advice and does not substitute for the advice of a qualified healthcare professional. This platform does not cover all existing information related to the possible uses, directions, doses, precautions, warning, interactions, adverse effects, or risks associated with the medication discussed in the platform and is not intended as a substitute for the advice of a qualified healthcare professional. The materials contained in this platform are for informational purposes only and do not constitute or imply endorsement, recommendation, or favoring of this medication by NCODA, which assumes no liability for and does not ensure the accuracy of the information presented. NCODA does not make any representations with respect to the medications whatsoever, and any and all decisions, with respect to such medications, are at the sole risk of the individual consuming the medication. All decisions related to taking this medication should be made with the guidance and under the direction of a qualified healthcare professional.
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Daiichi Sankyo and AstraZeneca are excited to announce that ENHERTU® (fam-trastuzumab deruxtecan-nxki) is now approved for a new indication.

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate that was recently approved for use in adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.1

ENHERTU has Boxed WARNINGS for Interstitial Lung Disease/Pneumonitis and Embryo-Fetal Toxicity. Please see the Important Safety Information below and the full Prescribing Information, including Boxed WARNINGS, and Medication Guide.

View a sample EMR treatment plan HERE and information for ENHERTU that reflects efficacy, safety, and clinical trial information HERE.

RECOMMENDED DOSAGE FOR LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER

The recommended dosage of ENHERTU for locally advanced or metastatic gastric and GEJ cancer is 6.4 mg/kg given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. Please see the full Prescribing Information for details on dose reductions and modifications.

PATIENT SELECTION CONSIDERATIONS

Select patients with locally advanced or metastatic gastric cancer based on HER2 protein overexpression or HER2 gene amplification. Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU.

ENHERTU4U ICD-10 CODES
Please update your organization’s systems to include relevant ICD-10 codes for gastric cancer. The ENHERTU4U website lists codes for your consideration: https://www.enhertu4u.com/hcp/coding-and-reimbursement.html

ENHERTU PACKAGE INFORMATION

Vial size1
NDC1
J-code3
One 100 mg single-dose vial
65597-406-01
J9358

Important Safety Information
Indication
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

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Accelerated approval of DARZALEX FASPRO-based combination regimen supported by the Phase 3 ANDROMEDA study demonstrating a significantly
higher hematologic complete response rate in this rare and serious blood cell disorder

January 15, 2021 (HORSHAM, Pa.) – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the U.S. Food and Drug Administration (FDA) approval of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), a subcutaneous formulation of daratumumab, in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd) for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis.1 DARZALEX FASPRO® is the first and only FDA-approved treatment for patients with this blood cell disorder that is associated with the production of an abnormal protein, which leads to the deterioration of vital organs, most notably the heart, kidneys and liver.2,3 This indication is approved under accelerated approval and is based on the hematologic complete response rate (hemCR) measure. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. DARZALEX FASPRO® is not indicated and is not recommended for the treatment of patients with light chain (AL) amyloidosis who have NYHA Class IIIB or Class IV cardiac disease or Mayo Stage IIIB outside of controlled clinical trials.

Read the Full Release HERE

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