Written by: Lisa Raff, PharmD, BCPS, BCOP Northwest Oncology & Hematology
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Description: This PQI will review appropriate patient identification and management techniques to ensure optimal benefit from telotristat ethyl therapy.

Background: A first in class oral tryptophan hydroxylase inhibitor, telotristat ethyl, is approved for use in combination with somatostatin analogues (SSA) therapy in adults with carcinoid syndrome diarrhea inadequately controlled by SSA. Carcinoid tumors are well-differentiated neuroendocrine tumors that typically originate in the digestive track or lungs. These tumors may secrete as many as 40 different bioactive products, with the most pronounced being serotonin, histamine, tachykinins, kallikrein and prostaglandins. Carcinoid syndrome diarrhea is thought to be caused by the overproduction and release of serotonin by the carcinoid tumor, resulting in stimulation of intestinal secretions as well as motility and inhibition of intestinal absorption.

Clinicians should be aware of this oral option for carcinoid tumor patients who exhibit diarrhea symptoms that continue to be refractory to SSA therapy.

PQI Process: Consider EMR review of all patients with neuroendocrine tumors and assess adequate control of diarrhea

Upon receipt of a new prescription for telotristat ethyl:

  • Verify initial dosage is 250mg orally three times a day
  • Ensure adult patient with the diagnosis of carcinoid syndrome is:
    • Currently receiving a long-acting SSA at a stable-dose (3 months of treatment at the same dose)
      • Depot octreotide
      • Long-acting lanreotide
    • Suffering from inadequately controlled diarrhea
  • Dosages >30 mg for depot octreotide and >120 mg for long-acting lanreotide may not be reimbursed by insurance companies as this is above the approved dosages. Additionally, administering at an interval of <4 weeks is also outside of the prescribing guidelines and may cause reimbursement issues.
  • Provide patients with refractory carcinoid symptoms (either during the dose escalation phase of the long-acting SSA or while waiting to receive telotristat ethyl) with a rescue short-acting octreotide prescription, if not already receiving, as well as an antidiarrheal. Initial dosing of short-acting octreotide is typically 100 mcg subcutaneously three times a day. This dose may be titrated up to 600 mcg per day
  • Telotristat ethyl can be administered concomitantly with antidiarrheals and/or short- acting octreotide, but the injection must be given at a minimum 30 minutes after the telotristat ethyl as octreotide may decrease the serum concentration
  • Consider screening for depression using an approved depression test questionnaire. Although preclinical trials with telotristat ethyl did not demonstrate significant central nervous system penetration, at higher doses (ex. 500 mg three times daily vs 250 mg three times daily) an increase in depression-related adverse events were reported (placebo = 6.7% vs telotristat ethyl 500 mg TID = 15.6%). Further examination of this adverse event is being explored in a phase III trial

Patient Centered Activities:

  • Educate patients receiving telotristat ethyl:
    • Response times
      • Response times vary, but they may need to allow the full 12 weeks of therapy to respond to the treatment
    • Bowel Habits
      • Monitor closely and if patient begins to experience constipation make their healthcare team aware
      • Report any severe or persistent bowel pain as intestinal perforation and bowel obstruction was observed in clinical trails
    • Nausea
      • Report so that an anti-nausea medication can be prescribed
      • Important to remember that many anti-nausea medications can cause constipation, so counsel patients to monitor closely
    • Administration
      • Take with food (meals preferred over a snack)
      • If used in combination with short-acting octreotide must inject the octreotide at least 30 minutes after the telotristat ethyl

References:

  1. Kulke MH, Horsch D, Caplin ME et al. Telotristat ethyl, a tryptophan hydroxylase inhibitor for the treatment of carcinoid syndrome. J Clin Oncol. 2016; 35: 14-23.
  2. Xermelo® (telotristat ethyl) [package insert]. The Woodlands, TX: Lexicon Pharmaceuticals Inc. 2017.
  3. Modlin IM, Kidd M, Latich I et al. Current status of gastrointestinal carcinoids. Gastroenterology. 2005; 128(6): 1717-51.
  4. Kvols LK. Metastatic carcinoid tumors and the malignant carcinoid syndrome. Ann N Y Acad Sci. 1994; 733: 464-70.

Supplemental Information:

Background on Carcinoid Syndrome Diarrhea:

Carcinoid syndrome is most commonly associated with metastatic tumors of the jejunum, ileum and cecum, most commonly in the setting of liver metastases, as the liver is responsible for inactivating the bioactive products secreted by the tumor into the bloodstream. These tumors secrete substances like serotonin which is then metabolized to 5-hydroxyindoleacetic acid (5- HIAA) and excreted in the urine. Patients suffering from carcinoid syndrome are known to have modified metabolism of tryptophan. In healthy individuals only about 1% of tryptophan is converted to serotonin, but in patients suffering from carcinoid syndrome up to 70% of tryptophan can be converted to serotonin. Serotonin however does not cause flushing in carcinoid syndrome; this symptom is thought to be due to other bioactive products released by the tumor. Figure 1 outlines the metabolism of tryptophan and serotonin.

 

Clinical Trial Experience:

TELESTAR was a phase III placebo-controlled trial that demonstrated a significant decrease in bowel movement frequency with the addition of telotristat ethyl to SSA therapy in patients with uncontrolled carcinoid syndrome with a manageable adverse event profile. Bowel movement (BM) frequency decreased by approximately two movements a day, and a responder analysis identified that more than 40% of patients receiving telotristat ethyl had a ≥30% decrease in BM frequency compared with 20% of patient receiving placebo.

The most common treatment-related adverse events reported in TELESTAR in patients receiving telotristat ethyl 250 mg were nausea (13.3%), headache (11.1%), increased gamma-glutamyl- transferase (8.9%), depression (6.7%), peripheral edema (7%), flatulence (6.7%), decreased appetite (6.7%) and pyrexia (6.7%).

Financial Assistance

 

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: Matthew Schulz, RPh Rocky Mountain Cancer Centers
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Description of PQI: The purpose of this PQI is to identify patients initiating everolimus therapy and could benefit from stomatitis prophylaxis with a steroid mouthwash.

Background: Stomatitis is a significant complication associated with mTOR inhibition. In BOLERO-2 patients receiving everolimus/exemestane (EVE/EXE), all grade stomatitis was 67%; 33% Grade 2 and 8% Grade 3. The median time to Grade 2 or worse onset was 15.5 days. The incidence of new stomatitis (Grade ≥ 2) plateaued at 6 weeks. In a meta-analysis, 89% of first stomatitis events occurred within 8 weeks. Topical steroids are used to treat aphthous ulcers; anecdotal use of topical steroid prophylaxis has been reported. A trial entitled SWISH revealed prophylactic use of 0.5 mg/5 mL dexamethasone oral solution markedly decreased the incidence and severity of stomatitis in patients receiving EVE/EXE for metastatic breast cancer and should be considered a new standard of care in this setting.

PQI process: Upon receipt of a new prescription for everolimus:

  • Identify if the patient may be a candidate for steroid rinse
  • Contact the oncologist to obtain a prescription for mouthwash:
    • Dexamethasone 0.5mg/5ml solution – swish 10ml for 2 minutes and spit out QID for initial 8 weeks *Do not eat or drink for 1 hour post mouth rinse*
  • Follow up within 7 days of starting everolimus/steroid mouth rinse

Patient Centered Activities:

  • Provide Oral Chemotherapy Education (OCE) sheet
  • Encourage patients to use rinse on a scheduled regimen, four times per day
  • Brush teeth with soft or extra soft tooth brush
  • Advise patients to immediately report any signs or symptoms of mouth sore

Supplemental Information:

 

 

 

Study

Stomatitis Grade (%)
All1234
BOLERO-2 (total)67342580
SWISH (at 8 weeks)19.817.42.400

References:

  1. Rugo, HS, Seneviratne, L, Beck JT, et. Al. Prevention of everolimus-related stomatitis in women with hormone receptor-positive, HER2-negative metastatic breast cancer using dexamethasone mouthwash (SWISH): a single-arm, phase 2 trial. The Lancet Oncology. Vol 18, Issue 5; 654-662, May 01, 2017 https://doi.org/10.1016/S1470-2045(17)30109-2.
  2. Baselga J, et Al. Everolimus in Postmenopausal Hormone-Receptor-Positive Advanced Breast Cancer (BOLERO-2). The New England Journal of Medicine. Vol 366, No 6; 520-529. February 9, 2012. https://www.nejm.org/doi/full/10.1056/nejmoa1109653.
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: Jon Suyko Pharm.D., BCPS, UC Health Highlands Ranch

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Description: The purpose of this PQI is to discuss the various indications for rucaparib (Rubraca).

Background: Rucaparib is an oral tricyclic indole and inhibitor of poly(ADP-ribose) polymerases (PARPs) PARP 1, PARP 2 and PARP 3, with antineoplastic activity.1 PARPs are a group of enzymes activated by single-strand DNA breaks. PARP inhibitors block the ability of PARP to repair DNA that has been damaged including the recruitment of other DNA repair proteins.2  Rucaparib selectively binds to PARP 1, 2 and 3 and inhibits PARP mediated DNA repair. The enhanced accumulation of DNA strand breaks ultimately promotes genomic instability and leads to cell arrest and apoptosis. This activity may also increase the cytotoxicity of DNA-damaging agents possibly reversing resistance to chemotherapy and radiation therapy.

Rucaparib is indicated as maintenance treatment in adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rucaparib is also indicated in adult patients with a deleterious BRCA mutation- associated metastatic castration resistant prostate cancer who have been previously treated with androgen receptor-directed therapy and taxane-based chemotherapy. Along with rucaparib approval, the FDA has approved next-generation sequencing (NGS)-based companion diagnostic to identify patients with advanced ovarian cancer eligible for treatment with rucaparib. The test detects alterations in BRCA1 and BRCA2 genes in the tumor tissue of ovarian cancer patients.

PQI Process:

  • Rucaparib initial dose for any indication is 600 mg (2 x 300 mg tabs) taken twice daily
  • No initial dose adjustment required for renal or hepatic impairment
  • May be taken with or without food
  • Treatment should be continued until disease progression or toxicity
  • If the patient is receiving rucaparib for metastatic castration-resistant prostate cancer (mCRPC) they should also be receiving a gonadotropin-releasing hormone (GnRH) analog
  • If the mCRPC patient is not receiving a GnRH they should have had a bilateral orchiectomy
  • Most common ADR’s requiring dose adjustment in ovarian cancer based on ARIEL 3 study3,4
    • Thrombocytopenia
    • Anemia
    • Nausea
    • Fatigue/asthenia
  • Most common ADR’s requiring dose adjustment in mCRPC based on Triton2 study3,4
    • Anemia
    • Asthenia/fatigue
    • Thrombocytopenia
    • Nausea

Table 1. Recommended Dose Modification Schedule for Adverse Reactions3

Dose ReductionDose
Starting Dose600 mg twice daily (2 x 300 mg tablets)
First Dose Reduction500 mg twice daily ( 2 x 250 mg tablets)
Second Dose Reduction400 mg twice daily ( 2 x 200 mg tablets)
Third Dose Reduction300 mg twice daily  ( 1 x 300 mg tablet)

 

Available Tablet Strengths:

  • 200 mg tablet – blue, round, film coated, “C2” imprint
  • 250 mg tablet – white, diamond, film coated “C25” imprint
  • 300 mg tablet – yellow, oval, immediate release, film coated “C3” imprint

Patient Centered Activities:

  • Patient Education
  • If the patient misses a dose they should skip the missed dose and resume their regular dosing schedule5
  • Rucaparib should be stored at room temperature, away from heat, moisture and light
  • Monitoring
  • Myelodysplastic syndrome/ acute myeloid leukemia have occurred, Grades 3 or 4 (8%) in patients taking rucaparib3
  • Monitor for hematologic toxicity at baseline and monthly
  • Monitor for symptoms of fatigue, anemia and AST/ALT elevation

Supplemental Information:

Rubraca® Connections Co-Pay program6

  • $0 Co-pay program for patients with commercial insurance
  • Patients may receive support up to $30,000 per calendar year

Rubraca® Connections Patient Assistance Program7

  • For patients with no health insurance or insurance that does not cover Rubraca®
  • Based on household income and diagnosis

Clovis4YOU™8 Daily patient support via text messaging

  • Medication and refill reminders
  • Nutrition tips and more 

References:

  1. National Center for Biotechnology Information. “PubChem Compound Summary for CID 9931954, Rucaparib” PubChemhttps://pubchem.ncbi.nlm.nih.gov/compound/Rucaparib. Accessed 25 June, 2021.
  2. NCI, S., May 20, 2021, & April 22, 2021. (2020, June 11). FDA Approves Olaparib, Rucaparib to Treat Prostate Cancer. National Cancer Institute. https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-olaparib-rucaparib-prostate-cancer.
  3. Rubraca (rucaparib) Package Insert Revised: 10/2020
  4. Rubraca (rucaparib) dosing, indications, interactions, adverse effects, and more. (2020, October 9). https://reference.medscape.com/drug/rubraca-rucaparib-1000121.
  5. In: IBM Micromedex® CareNotes® [database on the Internet]. Greenwood Village (CO): IBM Corporation; publication year [2021]. Retrieved June 21, 2021 from: www.micromedexsolutions.com. Subscription required to view.
  6. “Rubraca Connections” Co-Pay Program https://www.rubraca.com/ovarian-cancer/patient-support-resources/patient-savings-support-programs
  7. “Rubraca Connections.” Patient assitance Program https://www.rubracaconnections.com/.
  8. Clovis4You™ Patient Support Program https://www.rubraca.com/ovarian-cancer/clovis4you-support-program.
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: Samantha Larson, PharmD, M Health Fairview

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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 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: Autumn Alvarez, PharmD, BCPS, Blue Ridge Cancer Care
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Description:  The purpose of this PQI is to describe the indication, pharmacology and dosing of trilaciclib.

Background: Trilaciclib is a CDK 4/6 inhibitor indicated to decrease the incidence of chemotherapy-induced myelosuppression in patients undergoing chemotherapy with a platinum/etoposide or topotecan containing regimen for extensive stage small cell lung cancer (ES-SCLC).  It is administered prior to chemotherapy on all days of treatment. Trilaciclib is a transient inhibitor of CDK 4/6.  Hematopoietic stem and progenitor cell (HSPC) proliferation is dependent on CDK 4/6 activity. In clinical studies, trilaciclib increased the percentage of cells arrested in the G1 phase of cell division for up to 32 hours post-infusion for all bone marrow progenitor subsets evaluated.  This transient G1 arrest of  HSPCs contributes to the myeloprotective effect of trilaciclib.1 In the pivotal study (GIT28-05), treatment with trilaciclib decreased the incidence of severe neutropenia vs. placebo (2% vs 49%, P<0.0001).  Mean duration of severe neutropenia in cycle 1 was also decreased (1 day vs 4.7 days, P<0.0001).1 Additional clinical trials also showed benefits in decreased incidence of severe neutropenia vs. placebo.  Secondary endpoints for the studies included red blood cell (RBC) transfusions after week 5 and GCS-F support; although not statistically significant, trilaciclib decreased the need for platelet transfusions versus placebo.  Clinically significant differences in the need for supplemental GCS-F support was seen in the trilaciclib treatment group versus placebo (0.149 events/cycle vs 0.280 events/cycle, respectively, P = 0.0145).3

PQI Process:

  • Identify patients who are at high risk for myelosuppression who will be receiving treatment for ES-SCLC with a platinum/etoposide or topotecan based regimen and recommend the use of trilaciclib with that chemotherapy regimen
  • Upon order of trilaciclib administration confirm appropriateness of therapy
  • Review patient medication list as significant interactions are possible with cisplatin, dofetilide and dalfampiridine. Trilaciclib is an inhibitor of organic cation transport (OCT2), multidrug and toxin extrusion1 (MATE1) and MATE-2K.  Coadministration with OCT2, MATE1 and MATE-2K substrates may increase concentration and levels of those drugs leading to increased serious or life-threatening toxicities
  • Review the adverse events and recommended actions (see Supplemental Information)
  • Infusionsite reactions including phlebitis and thrombophlebitis are possible and occurred in 56% of the trilaciclib treated patients in clinical trials. Monitor for signs and symptoms of injection-site reactions during the infusion.  For mild to moderate injection-site reactions, flush line with at least 20 mL NS or D5W. For patient symptoms or discomfort, ice/cold packs or warm compresses can be used depending institutional policy/preferences
  • The most common adverse reactions are fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia
  • If trilaciclib is discontinued, wait 96 hours from the last dose of trilaciclib before resumption of chemotherapy only
  • Dosing:
    • Trilaciclib 240 mg/m2 is given over 30 minutes within 4 hours prior to start of chemotherapy on each day that it is given
      • The interval between trilaciclib doses on sequential days should not be more than 28 hours
    • Trilaciclib is supplied as a 300 mg vial and must be reconstituted with 19.5 mL NS or D5W for a concentration of 15 mg/mL
    • The diluted trilaciclib solution will be clear yellow
    • Trilaciclib must be further diluted in either NS or D5W for a final concentration between 0.5-3 mg/mL2 with in-line 0.2 micron filter (do not use polytetrafluoroethylene inline filter)

Patient Centered Activities:

  • Provide patient education regarding trilaciclib
  • Instruct the patient to notify the nurse of any irritation, swelling, pain, redness, tenderness, itchy skin that feels warm to the touch around the injection site during the infusion2
  • Educate patients to report worsening respiratory issues as interstitial lung disease/pneumonitis is a potential adverse effect that would warrant quick identification and treatment
  • Females of childbearing age should be informed that trilaciclib can harm an unborn baby
    • Effective method of birth control is necessary during treatment and for at least 3 weeks after the last dose
  • Counsel patient on disease state, treatment regimen, adverse reactions, and verify understanding
  • Provide patient with treatment calendar outlining planned treatment schedule

Supplemental Information

Table 11

Adverse ReactionSeverityRecommended Action
Injection-site reactions, including phlebitis and thrombophlebitisGrade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated

OR

Grade 4:  Grade 4: Life-threatening consequences; urgent interventions indicated

Stop infusion and permanently discontinue trilaciclib

 

Acute drug hypersensitivityGrade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL)Stop infusion and hold trilaciclib until recovery to ≤Grade 1 or baseline; then consider resuming trilaciclib

• If Grade 2 recurs, permanently discontinue trilaciclib

Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL

OR

Grade 4: Life-threatening consequences; urgent intervention indicated

Permanently discontinue trilaciclib
ILD/PneumonitisGrade 2 – SymptomaticHold trilaciclib until recovery to ≤Grade 1 or baseline; consider resuming trilaciclib

• If Grade 2 recurs, permanently discontinue trilaciclib

Grade 3: Severe symptoms; limiting self-care ADL; oxygen indicated

OR

Grade 4: Life-threatening respiratory compromise; urgent intervention indicated (ex. tracheotomy or intubation)

Permanently discontinue trilaciclib
Other toxicitiesGrade 3: Severe or medically significant but not immediately life-threatening; hospitaliza­tion or prolongation of hospitalization indicated; disabling; limiting self-care ADL

 

Hold trilaciclib until recovery to ≤Grade 1 or baseline; consider resuming trilaciclib

If Grade 3 recurs, permanently discontinue trilaciclib

Grade 4: Life-threatening consequences; urgent intervention indicated

 

Permanently discontinue trilaciclib

 

Table 21

IV Infusion Bag MaterialDiluentDiluted Storage Duration
Polyvinyl chloride (PVC),

Ethylene vinyl acetate (EVA),

Polyolefin (PO), or Polyolefin/polyamide (PO/PA)

D5WUp to 12 hours at 20°C to 25°C (68°F to 77°F)
PVC, EVA, or PONSUp to 8 hours at 20°C to 25°C (68°F to 77°F)
PO/PANSUp to 4 hours at 20°C to 25°C (68°F to 77°F)

 

References:

  1. CoselaTM (trilaciclib) Package Insert. G1 Therapeutics Inc; 2/2021.
  2. CoselaTM (trilaciclib) Patient Information. G1 Therapeutics Inc; 2/2021.
  3. CoselaTM (trilaciclib) for chemotherapy induced myelosuppression in Adult patients with Extensive-Stage Small cell lung cancer. AMCP DOSSIER 2/18/2021.

 

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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