Written by: Natasha Heimbigner, PharmD, Summit Cancer Centers
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Description of PQI: The use of immunotherapy in cancer treatment has expanded tremendously over the last several years. The most common adverse effects include dermatologic, gastrointestinal, hepatic, and endocrine toxicities. Management of immunotherapy-related rash is an important intervention for the patient’s quality of life and buy-in for continuation of therapy.

Background: Immunotherapy is being used increasingly in cancer treatment; improving outcomes for many patients with melanoma, non-small cell lung cancer, breast cancer, and a growing number of tumor types.1 Although these agents have a wide range of adverse effects, the most commonly seen is dermatologic. These dermatologic adverse effects can manifest weeks to months after the first treatment, manifesting as a maculopapular or pruritic rash.2,3,4 Other potential toxic skin reactions include but are not limited to bullous eruptions and Stevens–Johnson Syndrome so understanding the difference of these specific skin reactions as well is important.

PQI Process:

  • Identify high risk patients – all immunotherapy patients
    • Note: patients may be reluctant to bring up adverse effects that they are experiencing for fear of discontinuing treatment; ask directly if they have a rash
  • Determine the grading of the rash

    • Grade 1: Covers < 10% body surface area or without symptoms, with mild or localized itching
    • Grade 2: Covers 10-30% body surface area with or without symptoms, with intense or widespread itching
    • Grade ¾: Covers > 30% body surface area, limiting actives of daily living, severe itching, affects sleep, life threatening or requiring possible hospitalization

    PQI Process Continued:

    • Recommend appropriate treatment based on grade of rash, discuss therapy to physician, and document in EMR *dose reduction of immunotherapy is not recommended*
      • Grade 1
        • Use fragrance-free soaps for bathing and detergents for clothes
          • Consult with medically integrated team to determine best relief care for patient
        • Topical corticosteroids twice daily
          • Triamcinolone 0.1% lotion or fluocinonide 0.05% cream
      • Grade 2
        • Topical corticosteroids twice daily
          • Triamcinolone 0.1% lotion or fluocinonide 0.05% cream
        • Oral antihistamines or GABA agonists for pruritus
          • Hydroxyzine 10 mg TID or Gabapentin 300 mg TID or Pregabalin 50 mg TID
      • Grade 3
        • Hold immunotherapy until rash is grade 1 or symptoms have resolved
        • Oral corticosteroids until rash is grade 1 or symptoms have resolved
          • Prednisone 0.5-1 mg/kg/day (or equivalent)
      • Grade 4
        • Permanently discontinue immunotherapy
        • Consider topical antibiotics in combination with oral retinoids, IV corticosteroids, IM/IV antihistamines, IV Antibiotics and/or hydration

    Patient Centered Activities:

    • Provide education:
      • Counsel patient on all medications and provide Oral Chemotherapy Education (OCE) sheets as applicable
      • Proper skin care tips and tricks
      • Provide infection prevention education
      • Monitor skin and stress importance of calling provider if rash worsens

References:

  1. Linardou, Helena, and Helen Gogas. “Toxicity Management of Immunotherapy for Patients with Metastatic Melanoma.” Annals of Translational Medicine, AME Publishing Company, 4 July 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4971373/.
  2. “Toxicities Associated with Checkpoint Inhibitor Immunotherapy.” UpToDate, www.uptodate.com/contents/toxicities-associated-with-checkpoint-inhibitor-immunotherapy#H645515.
  3. “ICLIO.” Institute for Clinical Immuno-Oncology, accc-iclio.org/.
  4. National Comprehensive Cancer Network. Management of Immunotherapy-Related Toxicities (Version 1.2018). https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf.
Important notice: 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 Jennifer M. Hasiak O’Doherty, PharmD, Hematology Oncology Consultants, PC
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Description: This PQI will highlight strategies for appropriate dosing and management of adverse effects related to trifluridine and tipiracil treatment in metastatic colorectal cancer.

Background: Trifluridine and Tipiracil is indicated for the treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. RECOURSE trial showed a survival benefit of 7.1 months (trifluridine and tipiracil) versus 5.3 months (placebo). Grade 3 and greater adverse effects occurred due to neutropenia (38%), decreased appetite (4%), diarrhea (3%) and nausea/vomiting (2%). 

PQI process: Upon receiving a prescription for trifluridine and tipiracil:

  • Verify the dose is correct
    • 35 mg/m2 based on trifluridine component (maximum, 80 mg) orally twice daily within 1 hour of a meal on days 1- 5, and days 8 – 12, repeated every 28 days until disease progression or unacceptable toxicity
    • It is not recommended to start at a lower dose to prevent dose limiting toxicities.
  • Obtain complete blood counts prior to Day 1 and on Day 15 of each cycle
    • Make sure platelets are greater than or equal to 75,000/mm3 and ANC > 1500mm3 prior to the start of each cycle
  • Check liver function
    • Do not initiate therapy in patients with moderate to severe hepatic impairment (Bilirubin >1.5 ULN and any AST elevation)
  • Check renal function
    • CrCl 15-29: Reduce to 20 mg/m2 orally two times daily
      • Consider reduction to 15 mg/m2 orally two times daily if further reduction is needed
    • Withhold trifluridine and tipiracil for any of the following
      • Absolute neutrophil count (ANC) less than 500/mm3 or febrile neutropenia
      • Platelets less than 50,000/mm3 or Grade 3 or 4 non-hematological adverse reactions
      • After recovery, resume after reducing the dose by 5 mg/m2/dose from the previous dose level for the following only if there is more than a week delay of the next cycle:
        • Febrile neutropenia
        • Uncomplicated grade 4 neutropenia (recovered to ≥1,500/mm3) or thrombocytopenia

Timing of presentation of adverse events:

  • Cycles 1-3 are the cycles with the highest incidence of adverse events
    Neutropenia:
  • Dose holidays are preferred for neutropenia
  • Retrospective data shows neutropenia at the 1-month mark showed trend towards overall survival benefit2

Patient Centered Activities:

  • Provide Oncology Chemotherapy Education (OCE ) sheet
  • Provide Loperamide
  • Ensure patient has anti-nausea medications
  • Storage: If medication is stored outside of original container, throw medication away after 30 days
  • Handling: trifluridine and tipiracil is a cytotoxic drug – follow applicable special handling and disposal procedures
  • Provide Starter Kits
    • Contact your sales representative or call 1-844-824-4648
    • Visit TaihoPatientSupport.com

Co-Pay Assistance:

  • Patients with commercial paying insurance are eligible for co-pay support
  • Patients pay no more than Zero dollars ($0) per treatment cycle of trifluridine and tipiracil
  • Information regarding the program can be found at:
    • Call 1-844-824-4648
    • com

Dosing Guideline Summary:

  • Starting dosage: 35 mg/m2 twice daily rounded to nearest 5 mg increment and do not exceed 80 mg/dose or 160 mg/day
  • Active treatment days: Days 1 to 5 and 8 to 12 of each 28 day treatment cycle
  • Administration: take within 1 hour after completion of morning and evening meals to lessen the negative effect on neutrophil counts
    • Absence of food does not affect AUC but can cause CMAX to spike leading to adverse effects
    • No restriction on food type

 

References:

  1. Lonsurf® (trifluridine/tipiracil) [package insert]. Princeton, NY: Taiho Oncology, Inc.; 2019.
  2. Atsushi Ohtsu, Takayuki Yoshino, et. Al On Behalf of the RECOURSE Study Group. Onset of neutropenia as an indicator of treatment response in the phase 3 RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo in patients with metastatic colorectal cancer. Journal of Clinical Oncology 2017 35:4_suppl, 775-775.

Important notice: 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: Andrew Kowalski, PharmD and Osama Abdelghany, PharmD, MHA, BCOP -Smilow Cancer Hospital at Yale New Haven Health
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Description: There are a number of treatment options for patients with follicular lymphoma that has relapsed or is refractory to first line options. The purpose of this PQI is to discuss appropriate patient identification and clinical considerations around the use of 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. Copanlisib is an intravenous phosphatidylinositol 3-kinase (PI3K) inhibitor. PI3K pathways are often hyperactive in B-Cell malignancies. A phase II study in follicular lymphoma demonstrated an overall response rate of 59% with copanlisib. In 168 adults with exposure to copanlisib, the most common treatment related adverse events in any grade were hyperglycemia (54%), leukopenia (36%), fatigue (36%), diarrhea (36%), and hypertension (35%). Grade 3+ adverse events were observed for hyperglycemia (39%), leukopenia (27%), and hypertension (27%) and infections (14%).

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
      • In clinical trials, copanlisib induced hyperglycemia peaked 5-8 hours post-infusion and remained elevated 24 hours post-infusion
      • 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
    • In clinical trials, blood pressure remained elevated 6-8 hours post infusion
    • Withhold, reduce dose, or discontinue copanlisib depending on the severity and persistence of hypertension *review prescribing information for full details
  • Drug-Drug Interactions
    • Copanlisib is a major substrate of CYP3A4
    • Avoid concomitant use of strong CYP3A4 inhibitors
      • Potential: 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
  • 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. 2019.

Supplemental Information:

Select treatment options include:

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

Administration/Storage:

  • Reconstitute
    • Add 4.4 mL of sterile NS. Gently shake for 30 seconds, then let stand for 1 minute. If particulates remain, gently shake again and let sit for 1 minute
    • Final concentration 15 mg/mL
  • Storage
    • Reconstituted or diluted solution: 2-8 degrees C up to 24 hours
    • Avoid exposure to direct sunlight
  • Administration
    • Infuse over 1 hour
Important notice: 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: Katie Carter, PharmD, BCPS, IU Simon Cancer Center
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Description: The purpose of this PQI is to highlight tucatinib and its usage and management in advanced unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens in the metastatic setting.

Background: Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2, a growth factor receptor over-expressed in various types of cancers.1 Tucatinib binds to the HER2 protein, inhibiting its role in signaling pathways and ultimately the growth of HER2-expressing cells.

Tucatinib, in combination with trastuzumab and capecitabine, is being studied in the HER2CLIMB trial that enrolled patients with locally advanced unresectable or metastatic HER2 positive breast cancer who had previously been treated with trastuzumab, pertuzumab, or trastuzumab emtansine. Patients received either tucatinib 300 mg orally twice daily or placebo in addition to trastuzumab and capecitabine.2

 

 Tucatinib GroupPlacebo Group
PFS at 1 year33.1%12.3%
Median PFS duration7.8 months5.6 months
OS at 2 years44.9%26.6%
Median OS duration21.9 months17.4 months

 

Additionally, researchers analyzed the subgroup of patients with brain metastases and found significantly increased PFS with tucatinib in this patient population as well, reporting primary results of PFS at one year of 24.9% in the tucatinib group compared to 0% in the placebo group. Presented at the 2020 ASCO Annual Meeting, an exploratory analysis in the HER2CLIMB trial of intracranial efficacy in patients with brain metastases who received tucatinib combination versus placebo group: a 42% reduction in the risk of death, a 68% reduction in the risk of CNS disease progression or death, and an increase in intracranial response rate (47% vs. 20%) for patients who had active measurable intracranial lesions at baseline.5

PQI Process: Identify eligible HER2 positive patients as potential candidates for tucatinib. Upon receiving a prescription for tucatinib:

  • Verify appropriate starting dose: typically 300 mg by mouth two times daily
  • Confirm orders for capecitabine and trastuzumab
  • Drug interactions: avoid concomitant strong CYP3A4 and CYP2C8 inhibitors and inducers
  • When to adjust which agent:
    • All side effects should be assessed for relationship to tucatinib, capecitabine, and/or trastuzumab
    • Liver function abnormalities: tucatinib dose should be adjusted
    • Left ventricular ejection fraction (LVEF): tucatinib should be held if > 16% reduction from baseline, LVEF below limits of normal and > 10% reduction from baseline, or LVEF < 40%
    • QTc prolongation: tucatinib dose should be adjusted, regardless of relationship to drug

Dose adjustments:

Dose ReductionRecommended DoseHow to Supply
1st dose reduction250 mg PO BIDOne 150 mg tablet + two 50 mg tablets BID
2nd dose reduction200 mg PO BIDOne 150 mg tablet + one 50 mg tablet BID
3rd dose reduction150 mg PO BIDOne 150 mg tablet BID

 

Patient Centered Activities:

References:

  1. English DP, Rogue DM, Santin AD. HER2 expression beyond breast cancer: therapeutic implications for gynecologic malignancies. Mol Diagn Ther. 2013;17(2):85-99.
  2. Murthy RK, Loi S, Okines A, et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. NEJM. 2020; 382:597-609.
  3. Seattle Genetics. Available at https://www.seagen.com/science/pipeline/tucatinib.
  4. Tucatinib combination extends survival in HER2- positive metastatic breast cancer, including patients with brain metastases. The ASCO Post. Available at: https://www.ascopost.com/issues/january-25-2020/tucatinib-combination-extends-survival-in-her2-positive-metastatic-breast-cancer/. Published JAN 25, 2020.
  5. Lin NU, Borges V, Anders C, et al. Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial. JCO. 2020, JCO2000775. doi: 10.1200/JCO.20.00775.

Important notice: 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: Eric Dallara, RPh, New England Cancer Specialist
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Description:  Diarrhea is the main toxicity of neratinib treatment occurring in 95% of patients in the ExteNET trial on the Neratinib arm in which antidiarrheal prophylaxis was not protocol specified.1  Various prevention and treatment strategies for diarrhea have been studied and will be discussed in this PQI.

Background: Neratinib is indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab based therapy. The majority (95%) of patients experienced diarrhea in the first month of treatment in ExteNET.  Median time to onset of any grade diarrhea is 2 days (8 days for Grade 3) and median cumulative duration of diarrhea was 59 days (5 days for Grade 3). The Phase 2 CONTROL trial was designed to investigate various approaches to preventing and managing diarrhea in patients on neratinib, including various anti-diarrheal combinations, as well as a dose escalation arm. Mature data is available for budesonide and colestipol; interim data are available for dose escalation in Phase 2 CONTROL trial.4 All preventative strategies from the CONTROL trial reduced the incidence, duration, and severity of diarrhea, and also reduced neratinib discontinuation when compared to the pivotal ExteNET trial.

PQI Process: Upon receipt of neratinib prescription:

  • Consider dose escalation based on data from CONTROL trial (see supplemental information for dosing)
  • Diarrhea Prophylaxis – Diarrhea occurs in 95% of the patients without prophylaxis protocol
    • Begin prophylaxis with the first dose or neratinib and continue for 2 cycles depending on the regimen selected and the patient response
    • Ensure patient has instructions and supply of loperamide and consider colestipol or budesonide (see Supplemental Information for dosing)
    • Refer to Oncolytic Induced Diarrhea PQI
    • Identify drug-drug interactions and side effect profiles of loperamide, colestipol, and budesonide when making clinical recommendations
    • Consider weekly assessment of diarrhea throughout the first 2 cycles
  • Drug-Drug Interactions
    • Avoid concomitant use of PPIs
    • If H2-antagonists must be used, administer neratinib 2 hours before or 10 hours after
    • Other antacids (Tums, Maalox) should be separated by at least 3 hours
  • Verify in EMR that patient is scheduled for CMP to assess liver function
    • Consider monthly CMP for the first 3 months then every 3 months as clinically indicated 

Patient Centered Activities:

  • Neratinib should be taken with food and around the same time each day
    • Dose escalation – Take three tablets (120 mg) daily for 7 day, then four tablets (160 mg) daily for 7 days, then six tablets (240 mg) daily
    • Initiation without escalation – Take six tablets (240 mg daily) with loperamide during the first 56 days, then loperamide as needed to maintain daily bowel movements
  • Maintain adequate oral hydration throughout treatment unless otherwise indicated
  • Counsel on other possible side effects
    • Diarrhea (95%)
      • Voucher for 3-months of anti-diarrheal medication from the manufacturer
      • Advise patients to call office if diarrhea is uncontrolled with anti-diarrheal
    • Nausea (43%)
    • Abdominal pain (36%)
    • Vomiting (26%)
    • Stomatitis (14%)
  • Financial Assistance:
  • 3-month voucher available for anti-diarrheal agents
  • Traditional financial assistance for high medication costs available through PumaPatientLynx

References:

  1. NERLYNX® [Package Insert]. Los Angeles, CA: Puma Biotechnology, Inc.
  2. Hurvitz S, Chan A, Iannotti N, et al. Effects of adding budesonide or colestipol to loperamide prophylaxis on neratinib- associated diarrhea in patients with HER2+ early-stage breast cancer: CONTROL trial. Presented at: 40th Annual San Antonio Breast Cancer Symposium; Dec 5-9, 2017; San Antonio, TX. Poster P3-14-01.
  3. Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. Dec 2017;18(12):1688-1700. https://www.ncbi.nlm.nih.gov/pubmed/29146401.
  4. Barcenas CH, Hurvitz SA, Di Palma J, et al. Effect of prophylaxis on neratinib-associated diarrhea and tolerability in patients with HER2+ early-stage breast cancer: Phase II CONTROL trial. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting. May 31-June 4, 2019; Chicago, IL. J Clin Oncol. 2019;37:(suppl; abstr 548). https://bit.ly/2Xu86DO.

 

Supplemental Information:

Dosing Regimens from CONTROL study:

Loperamide:·      4 mg TID days 1-14, then 4 mg BID days 15-56
Budesonide·      9 mg/day for 1 cycle

·      + loperamide 4 mg TID days 1-14, then 4 mg BID days 15-56

Colestipol·      2 gm BID for 1 cycle + loperamide PRN or

·      + loperamide 4 mg TID days 1-14, then 4 mg BID days 15-28

Neratinib·      120 mg/day on days 1–7, then 160 mg/day on days 8–14,
then 240 mg/day through day 364 or

·      160 mg/day on days 1–14, then 200 mg/day on days 15–28,
then 240 mg/day through day 364

Dose Escalation Regimen:

  • 160 mg (4 tablets) daily days 1-14
  • 200 mg (5 tablets) daily days 15-28
  • 240 mg (6 tablets) daily days 29+

Note: Loperamide was given as needed in this arm of the CONTROL study

 

Dosage Adjustment for Diarrhea:

Grade 1 or 2 (<5 days) or Grade 3 (<2 days)

  • Maximize use of antidiarrheal agents and assess diet and aggravating substances
  • When diarrhea has improved to ≤ grade 1 or baseline, initiate loperamide 4 mg with each subsequent neratinib dose

Grade 2 (>5 days) or Grade 3 (>2 days) or any grade with complicating features of dehydration, fever, hypotension, renal failure, or grade 3/4 neutropenia):

  • Interrupt treatment. Modify diet; maintain fluid intake of ~2 L
  • If diarrhea improves to ≤ grade 1 in 1 week or less, resume neratinib at the same dose
  • If diarrhea improves to ≤ grade 1 in more than 1 week, resume neratinib at the next lower dose
  • When diarrhea has improved to ≤ grade 1 or baseline, initiate

loperamide 4 mg with each subsequent neratinib dose

Recurrent Grade 2 or more occurring at 120 mg once daily dose, or, Grade 4 diarrhea:

  • Permanently discontinue neratinib
Important notice: 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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