[PPT] - SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) PowerPoint Presentation

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SUPPORTIVE CARE NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN) ANTIEMETIC GUIDELINE UPDATES, VERSION 3.2018

MEENAKSHI SHELAT, PHARMD, BCOP

DARTMOUTH-HITCHCOCK MEDICAL CENTER NOVEMBER 2018

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DISCLOSURES

I have nothing to disclose related to the content of this presentation

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LEARNING OBJECTIVES

Explain the basic physiology of chemotherapy-induced nausea and vomiting
Review recent updates that highlight agents/dosages classified as highly

emetogenic to ensure adequate guideline-based prophylaxis

Recognize agents that are categorized as medium, low, and minimal

emetogenic risk to recommend appropriate therapy

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ADDRESSING CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING (CINV)

Need to overcome challenges with implementing guideline-based updates to

ensure optimal care for patients experiencing CINV

Education, training, communication, order-sets
Consider patient regimen and clinical, social, financial factors
Pharmacists play a critical role in education, communication, and counseling

Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016. Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92. 4

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PHYSIOLOGY

MECHANISMS OF ACTION

Neurokinin 1 receptor antagonist

(NK1RA)

5-hydroxytryptamine receptor

antagonist (5-HT3 RA)

https://www.researchgate.net/figure/Pathophysiology-of-chemotherapy-induced-nausea-and- vomiting_fig2_321927048 National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 5

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NK1 receptor antagonist
5-HT3 receptor antagonist
Dopaminergic receptor antagonist
Cannabinoid

https://openi.nlm.nih.gov/detailedresult.php?img=PMC4034105_pharmaceuticals-03-02930-g001&req=4

PHYSIOLOGY

MECHANISMS OF ACTION

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 6

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TYPES OF EMESIS

Chemotherapy-Induced (Intravenous, IV and Oral, PO)

Anticipatory, Acute, Delayed, Breakthrough, Refractory

Radiation-Induced

Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 7

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PATIENT-FOCUSED GOAL: PREVENTING NAUSEA AND VOMITING

≤ 24 hrs

Acute

High Moderate

> 24 hrs

Delayed

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 8

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PATIENT CASE AND DISCUSSION

Pt ND is a 62 year old female

Stage IIIC1 grade 2 endometrial cancer, s/p robotically assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node dissection

Past medical history: reports low alcohol intake
Plan to start paclitaxel 175 mg/m2 and carboplatin AUC 5, followed by pelvic

radiation therapy 50 Gy or 45 Gy with cisplatin for chemosensitization, with further chemotherapy to follow

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CINV IS MULTIFACTORIAL

Emetogenic risk of agents in regimen (high, moderate, low, minimal)
Female
Younger age (less than 50 yrs)
History of low alcohol intake
History of motion sickness
History of emesis during pregnancy

Heskith P. Oncologist. 1999; 4:191-6. National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016. Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92. 10

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DRUG CLASSES

Class NK1 receptor antagonist 5‐HT3 receptor antagonist Corticosteroids Thiobenzodiazepine

Examples aprepitant

‐ injectable emulsion ‐ oral (PO)

fosaprepitant ‐ intravenous (IV) netupitant (PO) rolapitant (PO)

ndansetron

palonosetron (IV) granisetron

‐ subcutaneous (SQ) ‐ intravenous ‐ transdermal

dolasetron

 oral

dexamethasone (dex)

lanzapine (PO)

netupitant/palonosetron (PO) fosnetupitant/palonosetron (IV) Monitoring/ Common Side Effects

CYP3A4 inhibitor

 dex dose reduction

Note: rolapitant is not a CYP3A4 inhibitor or inducer

Headache Constipation QTc/Cardiac Insomnia Hyperglycemia Dyspepsia CNS depression, sedation Weight gain Orthostatic hypotension QTc

Interaction‐ metoclopramide/ haloperidol – EPS

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Roila, F. et a. Annals of Oncology, Volume 27, Issue suppl_5, 1 September 2016, Pages v119–v133 11

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OTHER DRUG CLASSES/PATHWAYS

Class Benzodiazepine Cannabinoid Phenothiazine Dopaminergic receptor antagonist

Examples lorazepam dronabinol nabilone prochlorperazine promethazine metoclopramide* haloperidol** Monitoring/ Common Side Effects

CNS depression Useful for anxiety CNS depression May help appetite Increased risk of EPS CNS depression Sedation: promethazine > prochlorperazine Increased risk of EPS QTc *Diarrhea, but helps gastroparesis *Tardive dyskinesia **CNS depression

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 12

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RECENT CLINICAL TRIALS AND PAPERS

Trial Efficacy Safety A double-blind randomized phase II dose-finding study

f olanzapine 10 mg or 5 mg for the prophylaxis of

emesis induced by highly emetogenic cisplatin-based chemotherapy. Yanai T et al, Int J Clin Oncol. 2018 Apr;23(2):382-388.  Benefit in delayed emesis  5 mg (CR 85.7%, P < 0.001)  10 mg (CR 77.6%, P = 0.01)  Somnolence  5 mg: 45.5%  10 mg: 53.3% Papers Gilmore, J et al, Recent advances in antiemetics: new formulations of 5HT3-receptor antagonists. Cancer Manag

Res. 2018 Jul 3;10:1827-1857.

Navari, R et al, Evolving role of neurokinin 1-receptor antagonists for chemotherapy-induced nausea and

vomiting. Onco Targets Ther. 2018; 11: 6459–6478.

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TYPES OF EMESIS

Chemotherapy-Induced (Intravenous, IV and Oral, PO)

Anticipatory, Acute, Delayed, Breakthrough, Refractory

Radiation-Induced

Radiation therapy (RT) Upper abdomen/local sites, Total Body Irradiation (TBI), Chemotherapy and RT

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 14

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UPDATES REGARDING AGENTS AND REGIMENS

Type of Emesis/ Emetic Risk Agent Formulation High cisplatin carboplatin ≥ 4 anthracycline/cyclophosphamide Transplant regimen such as CBV IV IV IV IV Moderate to High enasidenib midostaurin niraparib PO PO PO Moderate liposomal encapsulation cytarabine and daunorubicin IV Low

laratumab

IV Minimal to Low abemaciclib brigatinib nertainib ribociclib PO PO PO PO Minimal avelumab rituximab and hyaluronidase IV SQ

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 15

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REFER TO MOST UPDATED VERSION OF GUIDELINES:

INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)

Type of Emesis/ Emetic Risk Day 1 Subsequent Days Days 2,3,4 for high; Days 2,3 for moderate CINV – High  NK1RA + 5-HT3 RA + dex  olanzapine + palonosetron + dex  olanzapine + NK1RA + 5-HT3 RA + dex  aprepitant PO if PO used Day 1 or ***dex  olanzapine  aprepitant PO if PO used Day 1,

lanzapine + dex

CINV - Moderate  5-HT3 RA + dex  olanzapine + palonosetron + dex  5-HT3 RA + dex (± NK1RA)  5-HT3 RA*** or dex  olanzapine  aprepitant PO if PO used Day 1 ± dex CINV - Low  dex  metoclopramide  prochlorperazine  5-HT3 RA CINV - Minimal No routine prophylaxis regimen RT – local TBI Chemo and RT  granisetron PO daily or ondansetron PO BID ± dex  granisetron PO daily or ondansetron PO BID/TID ± dex  See above

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. Journal of Oncology Practice 2017 13:12, 825-830 *** May not be needed 16

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REFER TO MOST UPDATED VERSION OF GUIDELINES:

INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)

Type of Emesis, Emetic Risk Day 1 Subsequent Days Days 2,3,4 for high; Days 2,3 for moderate CINV High  NK1RA + 5-HT3 RA + dex  olanzapine + palonosetron + dex  olanzapine + NK1RA + 5-HT3 RA + dex  aprepitant PO if PO used Day 1 or dex  olanzapine  aprepitant PO if PO used Day 1, olanzapine + dex CINV Moderate  5-HT3 RA + dex  olanzapine + palonosetron + dex  5-HT3 RA + dex (± NK1RA)  5-HT3 RA or dex  olanzapine  aprepitant PO if PO used Day 1 ± dex

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. Journal of Oncology Practice 2017 13:12, 825-830

*** May not be needed

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REFER TO MOST UPDATED VERSION OF GUIDELINES:

INCLUDING NATIONAL COMPREHENSIVE CANCER NETWORK (NCCN)

Type of Emesis, Emetic Risk Day 1 CINV Low  Dex  Metoclopramide  Prochlorperazine  5-HT3 RA CINV Minimal No routine prophylaxis regimen Radiation Therapy (RT) RT – local TBI Chemo and RT  Granisetron PO daily or ondansetron PO BID ± dex  Granisetron PO daily or ondansetron PO BID/TID ± dex  See respective emetic risk of agents

National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 Hesketh, PJ et al Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update Summary. Journal of Oncology Practice 2017 13:12, 825-830 18

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PATIENT CASE AND DISCUSSION

Pt ND is a 62 year old female

Stage IIIC1 grade 2 endometrial cancer, s/p robotically assisted total laparoscopic hysterectomy, bilateral salpingo-oophorectomy, sentinel lymph node dissection

Past medical history: reports low alcohol intake
Plan to start paclitaxel 175 mg/m2 and carboplatin AUC 5, followed by pelvic

radiation therapy with cisplatin for chemosensitization, with further chemotherapy to follow

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KEY TAKEAWAYS

Consider patient clinical scenario and use clinical judgment to ensure appropriate

coverage for chemotherapy or radiation therapy-induced nausea/vomiting

Recognize risk factors
Determine emetic risk of intravenous or oral chemotherapy agents/regimen
Apply guideline-based updates when possible
Consider drug interactions
Monitor side effects
Assess what agents work and/or try a different class or pathway

Barbour, Sally and Frame, David. Chemotherapy-induced Nausea and Vomiting: The Pharmacist’s Role in Integrating Clinical Guidelines into Patient Care. Presented as a Live Webinar. ASHP 2016. Aapro M et al. Ann Oncol. 2012 Aug;23(8):1986-92. National Comprehensive Cancer Network (NCCN) Guidelines Version 3.2018 – June 11, 2018 20

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POST-LECTURE QUESTIONS

Which of the following are risk factors for chemotherapy-induced nausea/vomiting (CINV)?

a) Younger age (less than 50 yrs) b) Female c) History of low alcohol intake d) all of the above

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POST-LECTURE QUESTIONS

For highly emetogenic chemotherapy agents, recent updates showed that the addition of what agent to prophylaxis helps to decrease the chance of nausea in adults and can also be used for breakthrough nausea/vomiting?

a) Diphenhydramine b) Olanzapine c)

Lorazepam

d) Metoclopramide

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POST-LECTURE QUESTIONS

For highly emetogenic chemotherapy agents, including for carboplatin with AUC ≥ 4, a recent update showed that the addition of what class of agents to prophylaxis helps to decrease the chance of nausea in adults (also can be used in pediatrics)?

a) GABA receptor antagonist b) Serotonin receptor antagonist c)

Neurokinin 1 receptor antagonist

d) H2 Antihistamine

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