Written by: Joshua Nubla, PharmD, NCODA

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Description: This PQI is developed to provide guidance to genomic testing with respect to larotrectinib.

 

Background: Larotrectinib is indicated for the treatment of adult and pediatric patients with solid tumors that:

  • Have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired
    resistance mutation
  • Are metastatic or where surgical resection is likely to result in severe morbidity, and
  • Have no satisfactory alternative treatments or that have progressed following treatment

This indication is approved under accelerated approval based on overall response rate and duration of response.1 As a key oncogenic driver, NTRK gene fusions are found in many types of solid tumors. Note that NTRK gene fusion is separate from general NTRK gene mutation. Within adult patients NTRK gene fusion frequency displays in estimated amounts such as the select tumors below:2

  • Lung: 0.2%-3.3%
  • GI Cancers: 0.7%-3.6%
  • Thyroid: 2.4%-12%
  • Sarcoma: 1%
  • Glioblastoma: 1.2%
  • Mammary Analogue Secretory Carcinoma: up to 100%

In October 2020, the FDA approved the next generation sequencing based FoundationONE CDx test (F1CDx) as a companion diagnostic for NTRK1, NTRK2, and NTRK3 in DNA or RNA isolated from tumor tissue from eligible patients. F1CDx is a next generation sequencing (NGS) based in-vitro diagnostic device capable detecting several mutations along with NTRK gene fusions.3

PQI Process:

  • Consider the following testing methods when planning for NTRK genomic testing:
    • NGS (Next generation sequencing)4 *preferred*
      • Utilize FoundationONE CDx test as available
      • Confirm the NGS assay used has the capacity to detect NTRK gene fusions (See Supplemental Information)
      • Ensure gene fusion testing of NTRK1NTRK2, and NTRK3are included in the panel order
      • It is important to note that if DNA does not detect NTRK, then the sample should be re-sequenced using RNA to ensure proper detection of NTRK
    • IHC (Immunohistochemistry)
      • Can be used as a screening diagnostic, however, sensitivity/specificity has been questioned
      • Following TRK IHC positive result, confirmation of NTRK gen fusion would be required for initiation of larotrectinib
    • FISH (fluorescence in situ hybridization)
      • Note that multiple tests would need to be run in order to detect NTRK gene fusions at multiple locations
      • Suited for tumor histologies that are pathognomonic for the ETV6-NTRK3 fusion such as Infantile Fibrosarcoma, secretory breast cancer, and MASC 

Patient Centered Activities:

Supplemental Information:

The following NGS testing laboratories are confirmed to detect all 3 NTRK gene fusions

  • Caris Life Sciences
  • Foundation Medicine
  • Integrated Oncology (LabCorp)/OmniSeq
  • NAVICAN
  • NeoGenomics Laboratories
  • Paradigm Diagnostics
  • PathGroup
  • Tempus 

References:

  1. VITRAKVI® [package insert]. Bayer HealthCare Pharmaceuticals Inc., Whippany, NJ.
  2. Sigal, D. S., Bhangoo, M. S., Hermel, J. A., Pavlick, D. C., Frampton, G., Miller, V. A., Ross, J. S., & Ali, S. M. Comprehensive genomic profiling identifies novel NTRK fusions in neuroendocrine tumors. Retrieved September 23, 2021, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6254675/.
  3. Food and Drug Administration. FDA Approves Companion Diagnostic to identify NTRK fusions in solid tumors for Vitrakvi®. https://www.fda.gov/drugs/fda-approves-companion-diagnostic-identify-ntrk-fusions-solid-tumors-vitrakvi.
  4. Vitrakvi®. Testing For Oncologists. https://www.hcp.vitrakvi-us.com/testing-for-oncologists/#oncolog-ngs-testing.

 

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: Jan Montgomery, PharmD, South Carolina Oncology Associates and Jacob Dygert, South University School of Pharmacy
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Description: To identify appropriate eligible patients for abemaciclib therapy based upon specific prognostic factors.

Background: Abemaciclib is indicated for the treatment of postmenopausal women with HR-Positive, HER2- Negative advanced or metastatic breast cancer. Abemaciclib may be used as monotherapy or in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy and in combination with fulvestrant with disease progression following endocrine therapy. In an exploratory analysis of the Monarch 3 and Monarch 2 (placebo + fulvestrant vs abemaciclib + fulvestrant) benefit was seen specifically in prognosis concerning: liver metastases, P-gR negative tumors, or high-grade tumors. The greatest benefit over placebo was seen in Monarch 2 among the subsection of patients with baseline liver metastases; the median progression free survival increased from 3.09 months (placebo) to 11.64 months (abemaciclib).6

PQI Process:

  • Obtain CBC with differential and platelets at baseline, every 2 weeks for the first 2 months, monthly for the next 2 months, then as clinically indicated
  • Identify patients with prognostic factors that may benefit patient outcomes in areas such as:
    • Visceral Liver Metastases
    • P-gR Negative Tumors
    • High-grade Tumors
  • Consider review of EMR for all current advanced breast cancer patients and those already on CDK4/6 inhibitors to assess for the prognostic factors above
  • Provide input with medically integrated team as needed to help benefit patient
  • Check liver function following the same schedule as CBC
  • Abemaciclib should not be given to pregnant women
    • Ensure proper use of birth control prior to and during therapy and 3 weeks past last dose
  • Monitor and educate patient to be aware of signs and symptoms of diarrhea, dehydration, venous thrombosis, or pulmonary embolism
  • Dosing Guideline Summary:
    • When used in combination with either an aromatase inhibitor (AI) or fulvestrant, abemaciclib 150 mg orally twice daily with or without food
    • When used as monotherapy abemaciclib 200 mg orally twice daily with or without food
    • See dose modification based on strong CYP3A4 inhibition
    • Be aware of dose adjustments for patients with severe hepatic impairment
    • Significant adverse effects to monitor include neutropenia and venous thromboembolism
    • Continue treatment until disease progression or unacceptable toxicity

Patient Centered Activities:3

References:

  1. VERZENIO ® [Package Insert]. Eli Lilly and Company , Indianapolis, IN. Accessed at: http://uspl.lilly.com/verzenio/verzenio.html#pi.
  2. https://nccn.org/professionals/physician_gls/default.aspx#breast.
  3. Lexicomp Online, Hudson, Ohio: Lexi-Comp, Inc.
  4. https://www.ncoda.org/Management-of-Abemaciclib-Associated-Diarrhea/.
  5. Gold Standard, Inc. Abemaciclib. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com.
  6. The benefit of abemaciclib in prognostic subgroups, presented by Matthew P. Goetz 12-/5/2017. Available at: https://lilly-medcomms.veevavault.com/ui/approved_viewer?token=1904-23eda912-9a67- 4a3a-847c- dab99ef3e133&email=a300f000005In3MAAS&orgid=00DG0000000BmPLMA0&AppDocId=a2u0f0000006
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: Trey McNiel, PharmD, Georgia Cancer Specialists
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Description: The purpose of this PQI is to discuss the clinical considerations around the use of acalabrutinib (Calquence®) to optimize the outcomes for patients with CLL/SLL.

Background: Acalabrutinib is a Bruton tyrosine kinase (BTK) inhibitor initially indicated for mantle cell lymphoma

(MCL) patients who have received one prior therapy. In late 2019, it received an indication for the treatment of

CLL/SLL either as monotherapy or in combination with obinutuzumab.1

Efficacy in the front-line setting was established by the ELEVATE-TN trial, demonstrating progression-free survival advantage of acalabrutinib when administered with or without obinutuzumab, when compared to obinutuzumab plus chlorambucil.2 At a median follow up of 28.3 months, acalabrutinib plus obinutuzumab improved PFS and ORR compared with obinutuzumab plus chlorambucil in the ELEVATE-TN trial (ORR 93% vs. 78.5%, PFS 93% vs. 47% respectively).2

The ASCEND trial displayed advantage in progression-free survival of acalabrutinib monotherapy in the relapsed/refractory setting when matched against investigator’s choice of rituximab product plus idelalisib or bendamustine.3 As monotherapy, acalabrutinib significantly improved PFS, but not ORR, in both the ELEVATE-TN and in the ASCEND trial. ELEVATE-TN trial ORR: 85% vs. 78.5%, ASCEND trial ORR: 80% monotherapy vs. 84% idelalisib plus rituximab (I-R) or bendamustine plus rituximab (B-R); ASCEND trial PFS: not reached in monotherapy vs. 16.5 months for the I-R/B-R arm.3

In ELEVATE-RR, the trial that put acalabrutinib head-to-head with ibrutinib as monotherapies, the primary endpoint concluded that acalabrutinib had a non-inferior PFS compared to ibrutinib. In addition, acalabrutinib had less cardiotoxicity and was discontinued less due to adverse events.4 At a median follow up of 41 months, acalabrutinib had a PFS of 38.4 months compared 38.4 months with ibrutinib. Acalabrutinib displayed less atrial fibrillation incidence than ibrutinib (9.4% vs 16.0%), less hypertension (9% vs 23%), and was discontinued less due to adverse events (15% vs 22%).

PQI Process:

Upon the receipt of a new prescription of acalabrutinib for CLL/SLL:

  • Verify dosage: the recommended starting dose of acalabrutinib is 100 mg every 12 hours, taken whole with water and with or without food
    • If dose is missed by more than 3 hours, it should be skipped and the next dose should be taken at its regularly scheduled time
    • Avoid in severe hepatic impairment
    • No dose adjustment needed in mild to moderate hepatic or renal impairment (use in severe renal impairment or with dialysis has not yet been evaluated
  • Review patient medication list for possible drug-drug interactions
    • Strong CYP3A4 inducer: if use cannot be avoided increase dosage to 200 mg every 12 hours
    • Strong CYP3A4 inhibitor: avoid use, but if the inhibitor is a short-term medication, stop acalabrutinib and resume after inhibitor is complete
    • Taken with moderate CYP3A4 inhibitor: reduce dosage to 100 mg daily
  • Acalabrutinib should be avoided with proton pump inhibitors
    • If other gastric reducing agents are used, recommend taking acalabrutinib 2 hours prior to taking a H2 receptor antagonist, if using an antacid separate dosing by at least 2 hours
  • In combination with obinutuzumab, acalabrutinib should be taken BEFORE the obinutuzumab

Adverse Events and Management1

CategoryOccurrenceAction
Fatal and serious infections, including opportunistic infectionsSerious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 19% of 1029 patients in clinical trialsConsider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor for signs and symptoms of infection and treat promptly
Fatal and serious hemorrhagic eventsMajor hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in 0.1% of 1029 patients in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 22% of patientsMonitor patients for signs of bleeding. Consider the benefit-risk of withholding acalabrutinib for 3-7 days pre-and post-surgery depending on type of surgery and the risk of bleeding

Caution in patients on antithrombotic agents

Grade 3 or 4 CytopeniasNeutropenia (23%), anemia (8%), thrombocytopenia (7%), and lymphopenia (7%), developed in patients. Grade 4 neutropenia developed in 12% of patientsMonitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted
Cardiac FactorsGrade 3 atrial fibrillation or flutter occurred in 1.1% of 1029 patients, with all grades of atrial fibrillation or flutter reported in 4.1% of all patients. The risk may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infectionMonitor for symptoms of arrhythmia (ex. palpitations, dizziness, syncope, dyspnea) and manage as appropriate
Skin CancerThe most frequent second primary malignancy was skin cancer, reported in 6% of patientsMonitor patients for skin cancers and advise protection from sun exposure

Dose Modifications1

EventEvent OccurrenceDose Modification (Starting dose = 100 mg every 12 hours)
Grade 3 or greater non-hematologic toxicities

Grade 3 thrombocytopenia with bleeding

Grade 4 thrombocytopenia

Grade 4 neutropenia lasting longer than 7 days

First and SecondInterrupt acalabrutinib

Once toxicity has resolved to Grade 1 or baseline level, acalabrutinib may be resumed at 100mg approximately every 12 hours

ThirdInterrupt acalabrutinib

Once toxicity has resolved to Grade 1 or baseline level, acalabrutinib may be resumed at a reduced frequency of  100 mg daily

FourthDiscontinue acalabrutinib

 

Patient Centered Activities:

  • Patient Education
    • Provide Oncology Chemotherapy Education (OCE) sheet and review with patient
    • Instruct patient to report any signs or symptoms of atrial fibrillation or flutter such as palpitations, dizziness, faint, chest discomfort
    • Patient should be made aware of the increased bleeding risk associated with acalabrutinib
      • Due to this risk, they may need to hold their medication prior to any procedures
    • Ensure patient has access to supportive medications for diarrhea such as loperamide
  • AstraZeneca Access 360® Program
    • Calquence® Co-Pay Savings Program (commercially insured patients)
    • AZ&Me Prescription Savings Program
      • Provides AstraZeneca medicines at no cost to qualifying patients
    • Patient Assistance foundations (federally insured patients)
  • CALQUENCECares®
    • Service through AstraZeneca to provide education and support during treatment

References:

  1. Calquence® (acalabrutinib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP.
  2. Sharman JP, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukemia (ELEVATE TN): a randomized, controlled, phase 3 trial. 2020 Apr 18;395(10232):1278-1291.
  3. Ghia P, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020;
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: Alyson Leonard, PharmD, BCPS, BCOP, Cone Health
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Description: Osimertinib is an indicated and preferred first line treatment option for patients with Epidermal Growth Factor Receptor (EGFR) gene mutation positive Non-Small Cell Lung Cancer (NSCLC) with Exon 19 deletion or exon 21 L858R and with EGFR T790M mutation positive disease with progression on/after EGFR tyrosine kinase inhibitor- based therapy.This PQI aims to provide guidance for initiating therapy with osimertinib.

Background: Osimertinib is a third-generation tyrosine kinase inhibitor that irreversibly binds to mutated EGFR, specifically to T790M, exon 21 L858R, and exon 19 deletion.1 Patients with EGFR mutation are seen to have a stronger response when treated with EGFR mutation directed therapy than the standard doublet chemotherapy.3 When available, multiplexed genetic sequencing panels are preferred over multiple single gene tests.4 EGFR mutations are more common in patients with East Asian ethnicity, no history of smoking, adenocarcinoma histology, and of female gender. However, any individual diagnosed with NSCLC may have an EGFR mutation regardless of race, gender, or smoking status and testing is imperative.5 EGFR mutations are found in ~10-23% in patients with adenocarcinomas of the lung.6,7

The FLAURA study found that osimertinib had a longer PFS when compared to erlotinib and gefitinib, 18.9 months vs 10.2 months, respectively. The rate of ≥ grade 3 adverse events were lower in the osimertinib arm, 35% vs 45%.2 Most common adverse events (any grade): diarrhea (41% to 58%), rash (34% to 58%), dry skin (23% to 36%), nail toxicity (22% to 35%), and stomatitis (15% to 29%).1

The BLOOM study evaluated the use of osimertinib in patients with EGFR mutation-positive advanced NSCLC who had progressed on prior EGFR-TKI therapy and had leptomeningeal disease. The BLOOM study included both T790M positive and T790M unselected patients. Patients were given osimertinib at an off-label increased dose of 160mg once daily with a median duration of response of 8.3 months.9

The ADAURA study evaluated the use of osimertinib in patients with EGFR mutation-positive stage 1B, II, or IIIA NSCLC with complete resection. Data was released early due to overwhelming efficiency. An 80% reduction in risk of recurrence/death across as stages of disease studied at the 3 year mark of this study.10 

PQI Process:

Upon receipt of an osimertinib prescription:1

  • Review EGFR mutational testing, including T790M, exon 21 L858R, and exon 19 deletion
  • Verify the dose/frequency is correct
  • Dosing:80 mg orally once daily with or without food
  • 160 mg orally once daily for leptomeningeal disease (off-label)9
  • If patient cannot swallow the osimertinib tablet whole, the tablet can be dissolved in water
  • Stir tablet in 60 mL of water – tablet will not completely dissolve but stir until dispersed into small pieces, rinse the container used to dissolve the tablet with 120mL – 240mL of water and drink immediately
  • Review patient medication list for possible drug-drug interactions
  • Strong CYP3A4 inducer: increase osimertinib starting dose to 160 mg once daily
  • Strong CYP3A4 inhibitors: No dos reduction, but monitor for adverse drug reactions
  • Evaluate patient for the need for baseline cardiac monitoring
  • Monitor LVEF in patients with cardiac risk factors
  • Monitor QTc and electrolytes in patients with history of QTc prolongation or on other QTc prolonging medications
  • QTc >500 msec on at least 2 separate ECGs: hold osimertinib, resume at 40 mg/d when QTc <481 msec or patient returns to baseline QTc
  • QTc with life threatening arrhythmias: permanently discontinue
  • Ensure supportive care is addressed (See Supplemental Information section)

 

Patient Centered Activities:

  • Patient Education
  • Provide Oncology Chemotherapy Education (OCE) sheet and Oncology Chemotherapy Education Supplemental Sheet
  • Instruct patient to report any adverse events, such as rash, nail changes, diarrhea, dry or itchy skin, nausea/vomiting, mouth sores, or inflammation
  • Ensure patient has access to supportive medications
  • Anti-nausea: ex. metoclopramide, prochlorperazine, or 5-HT3 receptor antagonist
  • Anti-diarrheal: ex. loperamide
  • Instruct patient to avoid sun exposure when possible. If unavoidable, utilize sunscreen
  • Medication Access Assistance
  • Co-Pay Foundation assistance
  • AstraZeneca Access 360 Patient Savings Program
  • AZ&ME AstraZeneca Prescription Savings Program  

References:

  1. Tagrisso (osimertinib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals.
  2. Soria JC, Ohe Y, Vansteenkiste J, et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. N Engl J Med. 2018;378(2):113-125.
  3. Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013;31(27):3327-34.
  4. Kalemkerian GP, Narula N, Kennedy EB, et al. Molecular Testing Guideline for the Selection of Patients with Lung Cancer for Treatment with Targeted Tyrosine Kinase Inhibitors: American Society of Clinical Oncology Endorsement of the College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology Clinical Practice Guideline Update. J Clin Oncol. 2018;36(9):911-919.
  5. Sag SO, Gorukmez O, Ture M, et al. Spectrum of EGFR gene mutations and ALK rearrangements in lung cancer patients in Turkey. Springerplus. 2016;5:482.
  6. Lazarus DR, Ost DE. How and when to use genetic markers for nonsmall cell lung cancer. Curr Opin Pulm Med. 2013;19:331–339.
  7. Cheng L, Alexander RE, MacLennan GT, et al. Molecular pathology of lung cancer: key to personalized medicine. Mod Pathol. 2012;25:347–369.
  8. Goss G, Tsai CM, Shepherd FA, et al. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018;29(3):687-693. doi: 10.1093/annonc/mdx820.
  9. Yang JC-H, Cho BC, Kim D-W et al.  Osimertinib for patients (pts) with leptomeningeal metastases (LM) from EGFR-mutant non-small cell lung cancer (NSCLC): updated results from the BLOOM study. J Clin Oncol  2017; 35(Suppl): abstr 2020.
  10. Wu YL, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723.
  11. Hirsh V, Blais N, Burkes R, Verma S, Croitoru K. Management of diarrhea induced by epidermal growth factor receptor tyrosine kinase inhibitors. Curr Oncol. 2014;21(6):329-36.
  12. Chu CY, Choi J, Eaby-sandy B, Langer CJ, Lacouture ME. Osimertinib: A Novel Dermatologic Adverse Event Profile in Patients with Lung Cancer. Oncologist. 2018;23(8):891-899.

 

Supplemental Information

Diarrhea management11 – The onset of diarrhea is typically within the first four weeks

Grade 1 Diarrhea (Mild)

Increase of <4 stools per day over baseline

Grade 2 Diarrhea (Moderate)

Increase of 4-6 stools per day over baseline

Grade 3 Diarrhea (Severe)

Increase of ≥7 stools per day over baseline

Start loperamide*Continue loperamide*Continue loperamide*
Continue osimertinib

 

Hold osimertinib if diarrhea does not improve after 48 hours

When diarrhea has improved to grade 1, restart at original dose

Hold osimertinib, when diarrhea has improved to grade 1, restart at reduced dose

**Permanently discontinue if diarrhea does not return to grade 1 within 14 days

*Loperamide dosing: 4 mg followed by 2 mg after each loose stool (up to 20 mg daily)

Rash management12

Grade 1 Rash (mild)

Covering <10% of BSA

Grade 2 Rash (Moderate)

Covering 10-30% of BSA

Grade 3 Rash (Severe)

Covering >30% of BSA

Topical corticosteroid:

triamcinolone 0.1% or hydrocortisone 2.5% daily or twice daily

Topical corticosteroid: triamcinolone 0.1% or hydrocortisone 2.5% twice dailyTopical corticosteroid:  clobetasol 0.05% cream twice daily
± topical antibiotic: clindamycin 1% gel or lotion

(alcohol free preparation)

AND oral antibiotic: 4-week course of an oral tetracycline antibioticAND oral antibiotic: 4-week course of an oral tetracycline antibiotic
Continue osimertinibContinue osimertinib, if rash is intolerable osimertinib can be held

 

Hold osimertinib, resume at 50% of original dose when patient has improved to ≤ grade 2
  • Rash or acne with osimertinib was found to occur at a lower rate when compared with standard EGFR-TKI therapy (osimertinib any grade: 58%, grade ≥3 1%; standard EGFR-TKI any grade: 78%, grade ≥3: 7%)
  • Due to the low frequency of acneiform rash, prophylactic management is not recommended, patient should contact their provider if toxicities appear. The onset of rash is typically within the first two weeks
  • Prutitus12
  • Grade 1-2:
  • Continue osimertinib unless symptoms are intolerable
  • Consider: topical antipruritic and oral antihistamine
  • Grade 3:
  • Hold osimertinib, resume or reduce dose when patient has improved to ≤ grade 2
  • Consider: topical oral antihistamine, GABA agonist, aprepitant, or doxepin
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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