Written by: Andrew Kowalski, PharmD and Osama Abdelghany, PharmD, MHA, BCOP
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Description of PQI:

There are a number of treatment options for patients with follicular lymphoma that has relapsed or is refractory to first-line options. In September 2017, the FDA approved copanlisib for the treatment of adults who have received at least two other previous therapies.

Background:

Non-Hodgkin’s lymphoma includes a variety of both aggressive and indolent malignancies. Follicular lymphoma is the most common subtype of indolent Non-Hodgkin’s Lymphoma.

Select treatment options include:

  • Cyclophosphamide, vincristine, prednisone (CVP) + obinutuzumab or rituxima
  • Rituximab
  • Lenalidomide +/- rituximab
  • Ibritumomab tiuxetan
  • Idelalisib (refractory to alkylator and rituximab)
  • Copanlisib (refractory to two prior therapies)
  • Duvelisib (refractory to two prior therapies)

Copanlisib is an intravenous phosphatidylinositol 3-kinase (PI3K) inhibitor. PI3K pathways are often hyperactive in B-Cell malignancies. The first FDA approved PI3K inhibitor for follicular lymphoma was idelalisib which is efficacious but is associated with potentially serious toxicities including hepatic dysfunction, colitis, autoimmune toxicity, and pneumonitis. A phase II study demonstrated an objective response rate of 43.8% with copanlisib. The most common treatment related adverse events were hyperglycemia (59.5%), hypertension (54.8%), fatigue (48.8%) and diarrhea (40.5%). Grade 3+ adverse events were observed in 31%, 4.8% and 11.9% of patients, respectively. The most common grade 3+ adverse events were lung infection (10.7%), diarrhea (3.6%) and febrile neutropenia (3.6%).

PQI Process:

Upon receipt of an order for copanlisib:

  • Ensure patient is an appropriate candidate for copanlisib and has received at least two prior therapies
  • Discuss potential risks of copanlisib therapy
    • Increased risk of infection
      • Monitor for signs and symptoms of infection, including pneumocystis jirovecii pneumonia (PJP)
      • For suspected PJP infection of any grade: Withhold copanlisib; if infection is confirmed, treat infection until resolution, then resume copanlisib at previous dose with concomitant PJP prophylaxis.
    • Hyperglycemia
      • Monitor blood glucose at least pre- and post-dose. It may be necessary to monitor more frequently as clinically indicated
      • Grade 3 or 4 hyperglycemia has occurred in >25% of patients. In clinical trials, copanlisib induced hyperglycemia peaked 5-8 hours post-infusion and returned to baseline within 24 hours
      • Pre-dose fasting blood glucose ≥160 mg/dL or random (non-fasting) blood glucose ≥200 mg/dL:
        • Withhold copanlisib until fasting glucose is ≤160 mg/dL or a random (non-fasting) blood glucose is ≤200 mg/dL.
    • Pre-dose or post-dose blood glucose ≥500 mg/dL:
      • First occurrence: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (non-fasting) blood glucose is ≤200 mg/dL. Reduce dose from 60 mg to 45 mg.
      • Subsequent occurrences: Withhold copanlisib until fasting blood glucose is ≤160 mg/dL, or a random (non-fasting) blood glucose is ≤200 mg/dL. Reduce dose from 45 mg to 30 mg. If hyperglycemia is persistent at the 30 mg dose, discontinue copanlisib.
  • Hypertension
    • Monitor blood pressure at least pre- and post-dose. It may be necessary to monitor more frequently as clinically indicated
    • Transient hypertension was observed in clinical trials in ~30% of patients but was not a significant cause of treatment delay
    • In clinical trials, blood pressure remained elevated 6-8 hours post infusion
    • Potential intervention:
      • For pre-dose elevation: withhold copanlisib until blood pressure is <150/90 (both systolic and diastolic) based on 2 consecutive measurements at least 15 minutes apart
      • For post-dose elevation: If elevation in blood pressure is life threatening, discontinue copanlisib. If antihypertensive therapy is not required, continue copanlisib at the previous dose. If antihypertensive treatment is necessary, consider copanlisib dose reduction from 60 mg to 45 mg (or from 45 mg to 30 mg). Discontinue copanlisib if blood pressure remains uncontrolled (>150/90) despite appropriate antihypertensive treatment.
    • Drug-Drug Interactions
      • Copanlisib is a major substrate of CYP3A4
      • Avoid concomitant use of strong CYP3A4 inhibitors
        • Potential intervention: If concurrent therapy cannot be avoided, reduce the copanlisib dose to 45 mg

Patient Centered Activities:

  • Educate patients on copanlisib therapy and recommend appropriate interventions:
    • Hyperglycemia
      • Monitor patients for signs of confusion, feeling sleepy, more thirst, more hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit
    • Hypertension
      • Monitor patients for signs/symptoms of high blood pressure like very bad headache or dizziness, passing out, or change in eyesight.
    • Diarrhea
      • Monitor for how many bowel movements occur each day. Recommend to patients to drink 8–10 glasses of water or fluid each day unless care provider has instructed to limit your fluid intake. Antidiarrheal medications be used to help control symptoms
    • Allergic or cutaneous reactions
      • Monitor for signs of rash, hives, itching, red/swollen/blistered/peeling skin with/without fever, wheezing, tightness in the chest/throat, trouble breathing/swallowing/talking, unusual hoarseness, or swelling of the mouth/face/lips/tongue/throat
    • Infections and pneumonitis
      • Monitor for any signs of lung or breathing problems like shortness of breath or other trouble breathing, fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal

References:

  1. Dreyling M, et al. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Annals of Oncology. 2017; 28: 2169-78. doi:10.1093/annonc/mdx289
  2. Aliqopa (copanlisib) [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc. 2017.
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Written by: Latha Radhakrishnan, PharmD, BCPS, BCOP
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Description of PQI:

The Granisetron Transdermal System is a 5-HT3 Receptor Antagonist (5-HT3 RA) that allows for an alternate medication delivery compared to oral or parenteral administration.  This can be particularly beneficial to those patients that do not have intravenous access, are unable to swallow, or have adherence issues. 

Background:

The Granisetron Transdermal System was approved in 2008 for the prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy (MEC and/or HEC) for up to 5 consecutive days1.  The National Comprehensive Cancer Network (NCCN) Antiemesis Practice Guideline includes granisetron transdermal system/patch as a 5-HT3 RA option for use in the prevention of acute and delayed intravenous MEC and HEC chemotherapy.  It is also a choice in high to moderate chemotherapy emesis prevention2. The pharmacokinetic profile of the formulation reveals continuous delivery of granisetron through the skin for over 6 days3Boccia et. al. conducted a double-blind, phase III, non-inferiority trial comparing the efficacy and tolerability of the granisetron transdermal system to daily oral granisetron for the control of CINV.  The results revealed non-inferiority to oral granisetron.  Both granisetron formulations were well tolerated with constipation being the most common side effect4.

Based on clinical practice experience, consider using the granisetron transdermal system in the following patient situations:

  1. Moderate to highly emetogenic multi-day chemotherapy
  2. Difficulty swallowing tablets due to oral mucositis, tumor location, vomiting, etc.
  3. Combination radiation + chemotherapy (head and neck regimens, etc.)
  4. Limited gut motility and absorption due to opioids or tumor location
  5. Difficulty remembering to take oral medications
  6. Refractory nausea and vomiting despite receiving appropriate preventative anti-emetics
    • Place patch on patients on the last day of multi-day intravenous chemotherapy

PQI Process:

Upon receipt of an order for granisetron transdermal system:

  • Ensure appropriateness of use in either MEC/HEC intravenous or high to moderate oral chemotherapy
  • Check start date of chemotherapy cycle
    • Apply 1 patch (3.1mg) 24-48 hours on clean, dry, intact skin on the upper outer arm prior to the start of c hemotherapy to the upper arm (do not cut)
    • Wear throughout chemotherapy treatment up to 7 days total
    • Remove at least 1 day (24 hours) after chemotherapy completed
  • Verify prescription coverage.  If issues, use Patient Rx Solutions to assist in coverage options
  • Discuss the use of surgical bandages or medical adhesive tape at the edges of the transdermal system to keep it in place
  • Provide a prescription for a rescue medication (i.e. prochlorperazine, metoclopramide, etc.) to assist with breakthrough nausea and vomiting.  Other 5-HT3 RA such as ondansetron should not be used as rescue medications to avoid QT prolongation, constipation, and headache.

Patient Centered Activities:

  • Application Instructions
    • Ensure that patients understand where to apply the patch
    • Educate on avoiding sunlight and heating sources (heating pads, tanning beds)
  • Patient Education
    • Review common side effects which include constipation and headache
      • Constipation – provide recommendations for a stimulant laxative (bisacodyl, sennosides, etc.) PLUS a stool softener
    • Explain when to apply and remove the patch – a calendar would assist
    • Remind to keep patch area covered under clothing and for another 10 days after the patch is removed to avoid potential skin reactions from natural or artificial sunlight
  • Financial Assistance
    • Patient Rx Solutions (https://www.patientrxsolutions.com or 1-800-676-5884)
      • Coverage option for uninsured patients
      • Co-pay Assistance Cards
      • Sancuso Patch Replacement Program– If chemotherapy is delayed or rescheduled

References:

  1. Sancuso [package insert, Bedminster, NJ: ProStrakan, Inc.; 2015.
  2. National Comprehensive Cancer Network. Antiemesis (Version 3.2018). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf Accessed January 3, 2018.
  3. Howell J, Smeets J, Drenth H, et al. Pharmacokinetics of a granisetron transdermal system for the treatment of chemotherapy-induced nausea and vomiting. J Oncol Pharm Practice. 2009; 15: 223 – 231.
  4. Boccia RV, Gordan LN, Clark G et al. Efficacy and tolerability of transdermal granisetron for the control of chemotherapy-induced nausea and vomiting associated with moderately and highly emetogenic multi-day chemotherapy: a randomized, double-blind, phase III study. Support Care Cancer.2011; 19: 1609-1617.
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Written by: Jody Agena, PharmD, MBA, BCOP
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Ibrutinib is a small molecule that acts as a potent, irreversible inhibitor of Bruton’s Tyrosine Kinase (BTK), a key component of the B-Cell receptor and cytokine receptor pathway.  BTK inhibition is vital for decreased malignant B-Cell proliferation and survival.  This molecule disrupts the proliferation of B-Cell cancers such as Mantle Cell Lymphoma, Chronic/Small Lymphocytic Leukemia, Marginal Zone Lymphoma, and Waldenstrom Macroglobulinemia. Managing both medication dosing and adverse effects are prime examples of key areas for additional intervention opportunities for improved patient health outcomes within the medically integrated team.

Continue reading Ibrutinib Management
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Written by: Kirollos S. Hanna, PharmD, BCPS, BCOP
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Patients receiving cancer therapies should be adequately assessed and managed to prevent chemotherapy-induced nausea and vomiting (CINV). 5-hydroxytryptamine (5-HT3) receptor antagonists, neurokinin-1 receptor (NK1R) antagonists, glucocorticoids, benzodiazepines, dopaminergic agents and other therapeutic classes have demonstrated substantial antiemetic activity. Despite proven efficacy, choice of therapy should be tailored to the individual patient based on the distinct types of CINV, patient risk factors and emetogenic potential of therapy. Guidelines for antiemetic therapy for intravenously administered chemotherapy according to the estimated risk of CINV are available from American Society of Clinical Oncology, National Comprehensive Cancer Network and the Multinational Association of Supportive Care in Cancer/ European Society for Medical Oncology1-3. Optimal control and prevention of CINV has been associated with improved adherence to cancer therapy stressing the importance of understanding and adhering to these guidelines4,5.
Continue reading Chemotherapy-Induced Nausea and Vomiting

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Written by: Natasha Heimbigner, PharmD
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The use of immunotherapy in cancer treatment has been expanding over the last several years. The most common adverse effect with these medications are dermatologic toxicities, gastrointestinal, hepatic, and endocrine toxicities. Management of immunotherapy related rash is an important intervention for the patient’s quality of life and buy in to continuation of therapy. Continue reading Managing Immunotherapy Treatment Related Rash

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