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Positive Quality Intervention: Enzalutamide (Xtandi) In Castration-Resistant Prostate Cancer or Metastatic Castration-Sensitive Prostate Cancer

Description: The purpose of this PQI is a summary of process for initiating and monitoring enzalutamide therapy in patients with either castration-resistant prostate cancer or metastatic castration-sensitive prostate cancer (mCSPC).1

Background: Enzalutamide is a pure androgen receptor inhibitor approved in August of 2012 for the treatment of castration-resistant prostate cancer. It gained approval for metastatic castration-sensitive prostate cancer in December of 2019.  The efficacy in patients with either castration-sensitive or castration-resistant prostate cancer was demonstrated in 5 major clinical trials: AFFIRM, PREVAIL, TERRAIN, PROSPER, ARCHES (see Supplemental Information section). Enzalutamide therapy in mCSPC is recommended both by National Comprehensive Cancer Network (Category 1)9 and American Urological Association Guidelines (Strong Recommendation; Evidence Level: Grade A)8 however is underutilized among new patients both in oncology and urology settings. Enzalutamide use in mCSPC should be considered as a potential and evidence-based option.

PQI Process: Identify patients of CRPC and mCSPC and evaluate eligibility for second-generation anti-androgens such as enzalutamide. Upon receipt of a new prescription for enzalutamide for prostate cancer:

  • Initial dosing for all indications is 160 mg once daily
    • Available as 40 mg tablets, 40 mg capsules, or 80 mg tablets
    • Swallow capsules or tablets whole
    • Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy
    • Reduce enzalutamide dose accordingly if co-administered with:
      • Strong CYP2C8 inhibitors – 80 mg daily
      • Strong CYP3A4 inducers – 160 mg to 240 mg once daily
    • Monitor LFTs at baseline and periodically throughout duration of therapy
    • Monitor blood pressure at baseline and throughout therapy
    • Dose modifications
      • Grade ≥3 toxicity or intolerable side effects, withhold dosing for 1 week or until symptoms improve to ≤ Grade 2, then resume at the same dose or a reduced dose (120 mg or 80 mg), if warranted
    • Review concomitant anticoagulation medications and adjust accordingly7

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) Sheet
  • Administration: Can be taken with or without food at the same time once daily
  • Review baseline labs and chronic medications – dose adjustment needed with concomitant CYP3A4 inducers or CYP2C8 inhibitors
  • Storage: Store at room temperature in the original bottle; do not remove desiccant from bottle

References:

  1. Xtandi (enzalutamide) [prescribing information]. New York, NY: Astellas Pharma US, Inc; 2020.
  2. Fizazi K, Scher HI, Miller K, Basch E, Sternberg CN, Cella D, Forer D, Hirmand M, de Bono JS. Effect of enzalutamide on time to first skeletal-related event, pain, and quality of life in men with castration-resistant prostate cancer: results from the randomised, phase 3 AFFIRM trial. Lancet Oncol. 2014 Sep;15(10):1147-56. doi: 10.1016/S1470-2045(14)70303-1. Epub 2014 Aug 4. Erratum in: Lancet Oncol. 2014 Oct;15(11):e475. PMID: 25104109.
  3. Beer TM, Armstrong AJ, Rathkopf D, et al. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: extended analysis of the phase 3 PREVAIL study. Eur Urol 2017;71(2):151-4.
  4. Shore ND, Chowdhury S, Villers A, et al. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomized, double-blind, phase 2 study. Lancet Oncol 2016;17(2):153-63.
  5. Hussain M, Fizazi K, Saad F, et al. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med 2018;378(26):2465-74.
  6. Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al: ARCHES: A randomized, phase III study of androgen-deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol 37:2974-2986, 2019
  7. Shatzel JJ, Daughety MM, Olson SR, et al. Management of Anticoagulation in Patients With Prostate Cancer Receiving Enzalutamide. J Onco Prac 2017;13(11):720-728.
  8. Lowrance WT, Breau RH, Chou R et al: Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I. J Urol 2021; 205: 14
  9. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2021. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed 2-15-2021.

Supplemental Information:

Xtandi Support Solutions®: Patient Support program

  • Enroll online at XtandiSupportSolutions.com or by calling 1-855-8XTANDI (1-855-898-2634)
  • Benefits Verification
  • Prior Authorization and Denial Appeals Assistance
  • XTANDI Quick Start+® Program
  • XTANDI Patient Savings Program
  • Astellas Patient Assistance Program
  • Financial Assistance Information for Medicare Patients
AFFIRM2PREVAIL3TERRAIN4PROSPER5ARCHES6
Patient PopulationmCRPCmCRPCmCRPCNonmetastatic CRPCmCSPC
Study DesignEnzalutamide + LHRH therapy (n=800)

vs placebo LHRH therapy (n=399)

Enzalutamide + LHRH therapy (n=872)

vs placebo LHRH therapy (n=845)

Enzalutamide + LHRH therapy (n=184)

Vs. bicalutamide + LHRH therapy (n=191)

Enzalutamide + LHRH therapy (n=933)

vs placebo LHRH therapy (n=468)

Enzalutamide + LHRH therapy (n=574)

vs placebo LHRH therapy

OutcomesMedian time to first skeletal event: Enzalutamide 16.7 months vs placebo 13.3 months

 

Pain progression at week 13: Enzalutamide 28% vs. placebo 39%

Median overall survival: Enzalutamide 35.3 months vs placebo 31.3 months

 

Median radiographic progression-free survival:  Not reached with enzalutamide + LHRH therapy vs 3.7 months with placebo + LHRH therapy

Median radiographic progression-free survival: Enzalutamide group 19.5 months vs bicalutamide group 13.4 months

 

Median progression-free survival: Enzalutamide patients 15.7 months and bicalutamide patients 5.8 months

Median metastasis-free survival: 3 years with enzalutamide therapy vs 14.7 months with placebo

 

First use of subsequent prostate cancer therapy was delayed by: Median of 3 years with enzalutamide + LHRH therapy vs. 17.7 months with placebo + LHRH therapy

 

Risk of radiographic disease progression or death:

61% reduction with enzalutamide + LHRH therapy vs placebo + LHRH therapy

 

Risk of starting a new antineoplastic therapy: 72% reduction with

enzalutamide + LHRH therapy vs placebo + LHRH therapy

*mCRPC-metastatic castration-resistant prostate cancer, LHRH-luteinizing hormone-releasing hormone, CRPC-castration-resistant prostate cancer, mCSPC – metastatic castration-sensitive prostate cancer


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: Lauren Trisler, PharmD, BCOP – Carle Cancer Center
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Daratumumab injection is an anti-CD38 monoclonal antibody (mAb) FDA approved for use in a range of multiple myeloma patients including first line, transplant ineligible and relapse/refractory.1 The subcutaneous formulation (DARZALEX FASPRO) is not indicated for front-line transplant eligible patients but is indicated for varied multiple myeloma indications (review supplemental information for reference)6. This PQI will provide guidance for optimal administration and management of both daratumumab infusions and subcutaneous formulation.

Continue reading Daratumumab (Darzalex®) for Multiple Myeloma

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Positive Quality Intervention: Pralsetinib Management for Metastatic RET Fusion-positive Non-Small Cell Lung Cancer

Description:

Pralsetinib is an oral Rearranged during Transfection (RET) tyrosine kinase inhibitor (TKI) that inhibits oncogenic RET fusions and mutations.1 The purpose of this PQI is to review pralsetinib’s role in therapy, management of adverse effects and potential drug interactions, and to recommend patient follow up associated with pralsetinib treatment.

Background:

The phase I/II ARROW trial examined pralsetinib for the treatment of RET fusion-positive metastatic non-small cell lung cancer (NSCLC).1,2 In the dose expansion phase of the study, all patients received pralsetinib at a dose of 400 mg once daily. The trial included 87 patients who had previously undergone treatment with platinum chemotherapy. Overall response rate in these patients was 57% (95% CI: 46%, 68%) with 5.7% of patients achieving a complete response. Responses of 6 months or greater were observed in 80% of patients who responded to pralsetinib. The study population also included 27 patients who had not yet received any treatment. Overall response rate in these treatment-naïve patients was 70% (95% CI: 50%, 86%) with a complete response observed in 11% of patients. A duration of treatment response of 6 months or greater was seen in 58% of patients.

Adverse effects seen in 25% or more of patients treated with pralsetinib include increase in liver enzymes, alkaline phosphatase and serum creatinine; decrease in hemoglobin, lymphocytes and neutrophils; fatigue, constipation, musculoskeletal pain, and hypertension.1 Interstitial lung disease (ILD)/pneumonitis occurred in 10% of patients who received pralsetinib, including 2.7% with Grade 3-4, and 0.5% with fatal reactions.1

PQI Process:

Upon receipt of an order for pralsetinib:

  • Ensure patient is an appropriate candidate based on diagnosis of RET fusion-positive metastatic NSCLC
    • FDA approved companion diagnostic test for RET fusion: Oncomine Dx Target (ODxT) Test (Life Technologies Corporation)
    • Starting dose of pralsetinib is 400 mg by mouth once daily on an empty stomach
      • No food should be eaten for at least two hours prior to and at least one hour after pralsetinib dose
    • Review patient’s current prescriptions for potential drug interactions
      • Avoid strong CYP3A4 inhibitors and inducers
  • Verify monitoring parameters:
    • Baseline: AST, ALT, blood pressure, pregnancy status in females of reproductive potential
    • AST/ALT every 2 weeks for first 3 months of therapy, then monthly or as clinically indicated
    • Blood pressure after 1 week of therapy then at least monthly or as clinically indicated
    • Signs/symptoms of interstitial lung disease/pneumonitis, hemorrhage, and impaired wound healing

 

Recommended Pralsetinib Dose Reduction for Adverse Reactions

Dose reductionRecommended dosage
Usual (initial dose)400 mg once daily
First dose reduction level300 mg once daily
Second dose reduction level200 mg once daily
Third dose reduction level100 mg once daily
Permanently discontinue pralsetinib if patient unable to tolerate 100 mg once daily

Pralsetinib Dosage Adjustments for Toxicities

ToxicitySeverityPralsetinib dose adjustment
Hemorrhagic eventsGrade 3/4Withhold pralsetinib until recovery to baseline or Grade 0 or 1.

Discontinue pralsetinib for severe or life-threatening hemorrhagic events.

HypertensionGrade 3Initiate or optimize hypertensive therapy. Withhold pralsetinib for grade 3 hypertension that persists despite management with optimal antihypertensive therapy. Resume pralsetinib at a reduced dose when hypertension is controlled.
Grade 4Discontinue pralsetinib.
HepatotoxicityGrade 3/4Withhold pralsetinib and monitor AST/ALT once weekly until resolution to Grade 1 or baseline.

Resume at reduced dose. If hepatotoxicity recurs at Grade 3 or higher, discontinue pralsetinib

Pralsetinib Dosage Adjustments for Toxicities continued

ToxicitySeverityPralsetinib dose adjustment
Pulmonary toxicity (interstitial lung disease [ILD])/pneumonitis)

 

Grade 1/2Withhold pralsetinib until resolution, then resume pralsetinib at a reduced dose. Permanently discontinue pralsetinib for recurrent ILD/pneumonitis.
Grade 3/4Permanently discontinue pralsetinib for confirmed ILD/pneumonitis.
Other adverse reactionsGrade 3/4Withhold pralsetinib until improvement to ≤ grade 2, then resume pralsetinib at a reduced dose.

 

Permanently discontinue pralsetinib for recurrent grade 4 adverse reactions.

 

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) sheet
  • Counsel to administer orally
    • Review importance of taking on an empty stomach
  • Review baseline labs and chronic medications
  • Proper sign/symptom monitoring
  • Evaluate if patients have missed any doses between cycles to determine if interventions are needed such as reminders, calendars, pill box, etc.

References:

  1. Blueprint Medicines Corporation. Available at https://www.blueprintmedicines.com/uspi /GAVRETO.pdf. Accessed December, 2020.
  2. Gainor JF, Curigliano G, Kim D-W, et al. Registrational dataset from the phase I/II ARROW trial of pralsetinib (BLU-667) in patients with advanced RET fusion+ non-small cell lung cancer (NSCLC).[abstract]. JClin Oncol 2020;38:Abstract 9515.

Supplemental Information:

YourBlueprint patient support program

  • Co-pay assistance for commercially insured patients
  • Free drug program for uninsured and underinsured patients
  • Case managers available
  • Enroll online or by calling 1-888-BLUPRNT (1-888-258-7768)

 

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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Positive Quality Intervention: Selpercatinib Genomic Testing Management

Description:

This PQI is developed to provide guidance to genomic testing with respect to selpercatinib (Retevmo®).

Background:

RET-altered cancers include both RET fusions and RET mutations. Both alterations involve activating RET signaling pathways that promote unwanted cell proliferation in cancers. NCCN guidelines for NSCLC include a Category 2A recommendation for RET testing as part of broad molecular profiling in routine clinical practice. In multiple guidelines, RET testing is considered as part of a larger initial panel or secondary single analyte test following negative results for other genetic variants such as EGFR, ALK, and ROS1. Molecular testing within RET-mutated medullary thyroid cancer (MTC) is applicable as approximately 50% of patients with sporadic MTC have somatic RET mutations. In American Thyroid Association, NCCN, and ESMO guidelines, RET testing should be considered within the MTC space. Next generation sequencing (NGS) analyzes DNA and/or RNA when detecting RET. This method requires a small amount of tissue for multiplex testing for many common and rare cancer-related biomarkers. Tissue testing is often considered as RET alteration may not be found in the blood through liquid biopsy and up to 30% of RET alterations can be missed if only ctDNA is tested. There are multiple testing methods for RET that will help determine patient eligibility for selpercatinib, noting that indicated tumor types are associated with specific alterations (Review Supplemental Information section for approved indications).

RET alteration to testAssociated tumor type(s)
RET-fusionNSCLC, Thyroid
RET-mutationMTC

PQI Process:

  • Consider the following preferred testing methods when planning for RET genomic testing:
    • Next generation sequencing (NGS) when applicable
      • Account for 2-4 weeks for test completion
      • Both DNA and RNA-based NGS testing methods are appropriate and care team should discuss the general advantages and disadvantages of both
        • RNA-based NGS is able to reveal unbiased fusion information and there are no intron coverage issues 5,10
      • Reverse Transcription-PCR
        • Quick and relatively inexpensive; test completion with 1-2 days
        • PCR testing is designed predominantly for fusions and RET fusion frequency is underestimated
      • FISH
        • High rate of false positive/false negative
        • Should only be considered in rare circumstances (eg. if NGS or RT-PCR are not available)
      • Provide testing schedule to patient

Patient Centered Activities:

  • Provide education to patients regarding genetic testing and what to expect
  • Prepare care team for timely turnaround time of testing results

Supplementary Information:

Selpercatinib is a kinase inhibitor indicated for the treatment of:

  • Adult patients with metastatic RETfusion-positive non-small cell lung cancer (NSCLC)*
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy*
  • Adult and pediatric patients 12 years of age and older with advanced or metastatic RETfusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)*

*This indication is approved under accelerated approval based on overall response rate and duration of response.15

References:

  1. Normanno N, Denis MG, Thress KS, et al. Guide to detecting epidermal growth factor receptor (EGFR) mutations in ctDNA of patients with advanced non-small-cell lung cancer. 2017;8(7):12501-12516. https://doi.org/10.18632/oncotarget.13915
  2. Meric-Bernstam F, Johnson A, Holla V, et al. A decision support framework for genomically Informed investigational cancer therapy. 2015;107(7). https://doi.org/10.1093/jnci/djv098
  3. Drilon A, Hu ZI, Lai GG, et al. Targeting RET-driven cancers: lessons from evolving preclinical and clinical landscapes. Nat Rev Clin Oncol. 2018;15(3):151-167. https://doi.org/10.1038/nrclinonc.2017.175
  4. Mulligan LM. RET revisited: expanding the oncogenic portfolio. Nat Rev Cancer. 2014;14(3):173-186. https://doi.org/10.1038/nrc3680
  5. Garinet S, Laurent-Puig P, Blons H, Oudart JB. Current and future molecular testing in NSCLC, what can we expect from new sequencing technologies? J Clin Med. 2018;7(6):144. https://doi.org/10.3390/jcm7060144
  6. Lee SE, Lee B, Hong M, et al. Comprehensive analysis of RET and ROS1 rearrangement in lung adenocarcinoma. Mod Pathol. 2015;28(4):468-479. https://doi.org/10.1038/modpathol.2014.107
  7. Chen F, Clark DP, Hawkins AL, et al. A break-apart fluorescence in situ hybridization assay for detecting RET translocations in papillary thyroid carcinoma. Cancer Genet Cytogenet. 2007;178(2):128-134. https://doi.org/10.1016/j.cancergencyto.2007.07.006
  8. Musholt TJ, Staubitz JI, Cámara RJ, et al. Detection of RET rearrangements in papillary thyroid carcinoma using RT-PCR and FISH techniques – a molecular and clinical analysis. Eur J Surg Oncol. 2019;45(6):1018-1024. https://doi.org/10.1016/j.ejso.2018.11.009
  9. Go H, Jung YJ, Kang HW, et al. Diagnostic method for the detection of KIF5B-RET transformation in lung adenocarcinoma. Lung Cancer. 2013;82(1):44-50. https://doi.org/10.1016/j.lungcan.2013.07.009
  10. Drilon A, Wang L, Arcila ME, et al. Broad, hybrid capture-based next-generation sequencing identifies actionable genomic alterations in lung adenocarcinomas otherwise negative for such alterations by other genomic testing approaches. Clin Cancer Res. 2015;21(16):3631-3639. https://doi.org/10.1158/1078-0432.CCR-14-2683
  11. Planchard D, Popat S, Kerr K, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018;29(suppl 4):iv192-iv237. http://dx.doi.org/10.1093/annonc/mdy275. Published correction appears in Ann Oncol. 2019;30(5):863-870. http://dx.doi.org/10.1093/annonc/mdy474
  12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Guideline for Thyroid Carcinoma V.1.2020. © National Comprehensive Cancer Network, Inc 2020. Accessed June 19, 2020. To view the most recent and complete version of the guideline, go online to org.
  13. Wells SA Jr., Asa SL, Dralle H, et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567-610. http://dx.doi.org/10.1089/thy.2014.0335
  14. Pacini F, Castagna MG, Brilli L, et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(suppl 7):110-119. https://doi.org/10.1093/annonc/mds230
  15. RETEVMO [package insert]. Lilly USA, LLC, Indianapolis, IN; January 2021

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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