Update on Oral Oncolytics: A Focus on Hematology Drugs

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1-11-2020

Update on Oral Oncolytics: A Focus on Hematology Drugs Update on Oral Oncolytics: A Focus on Hematology Drugs

Monica Tadros Miami Cancer Institute, [email protected]

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Citation Citation Tadros, Monica, "Update on Oral Oncolytics: A Focus on Hematology Drugs" (2020). All Publications. 3382. https://scholarlycommons.baptisthealth.net/se-all-publications/3382

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Update on Oral Oncolytics: A Focus on Hematology Drugs

Presenter: Monica Tadros, Pharm.D., BCPS

Miami Cancer Institute, Baptist Health South Florida

[email protected]

Objectives

Review the history of oral oncolytics for hematologic malignancies

Explore the different challenges associated with oral oncolytics

Discuss recently approved oral oncolytics for hematologic malignancies

Explain the role of the pharmacist in mitigating the challenges associated with oral oncolytics

Abbreviations/Acronyms CML: Chronic myeloid leukemia

BTK: Bruton’s tyrosine kinase

IDH: Isocitrate dehydrogenase

PI3K: Phosphoinositide 3-kinase

FLT3: FMS-like receptor tyrosine kinase-3

HDAC: Histone deacetylase

JAK: Janus Kinase

BCL-2: B-cell lymphoma 2

AML: Acute myeloid leukemia

MOA: Mechanism of action

FDA: Food and Drug Administration

LFT: Liver function tests

CR: Complete response / remission

CRh: Complete response with partial hematologic recovery

CRi: Complete remission with incomplete count recovery

LDAC: Low dose cytarabine

CLL: Chronic lymphocytic leukemia

SLL: Small lymphocytic lymphoma

FL: Follicular lymphoma

URI: Upper respiratory infection

PCP: Pneumocystis pneumonia; Primary care physician

ORR: Overall response rate

CI: Confidence interval

ECOG: Eastern Cooperative Oncology Group

MCL: Mantle cell lymphoma

AE: Adverse effects

GI: Gastrointestinal

PFS: Progression free survival

GVHD: Graft-versus-host disease

HSCT: Hematopoietic stem cell transplant

HR: Hazard ratio

OS: Overall survival

R/R: Relapsed refractory

SC: Subcutaneous

Definitions

What is an oral oncolytic?

Oral cytotoxic agent or small molecule inhibitor that targets surface proteins, tumor pathways, or receptors

Macker E, et al. J Clin Oncol. 2018; 15(4):e346-355.

History Traditional oral chemotherapy agents available since 1950’s

Examples: Chlorambucil, cyclophosphamide, MTX

In subsequent 50 years, 27 oral agents approved (~1 every 2 years)

Shifting mechanisms of action

Alkylating agents & antimetabolites targeted therapies

First FDA-approved small molecular inhibitor for the

treatment of CML

American Association for Cancer Research. Landmarks in Cancer Research. Retrieved from: https://www.aacr.org/Documents/Landmarks.pdf

Current Landscape Prescription of oral oncolytics is becoming more common

Substantial increase in oral oncolytic approvals in the past several years

Make up ~25% of the oncology market

Up to 35% of drugs in clinical trials are oral oncolytics

Dillmon MS, et al. J Clin Oncol. 2019; 37:1-12

Mosely WG, Nystrom JS. Community Oncology. 2009; 6:358-61

Advantages of Oral Chemotherapy

Patient convenience Fewer clinic visits (less travel time, time away from work, associated costs)

Flexibility for timing and location of administration

No need for intravenous access (less infections, pain)

Limited use of healthcare resources (inpatient/ambulatory services) Less use of supplies, ancillary equipment and personnel (nurses)

Better quality of life More time home with family

Less interruptions of daily activities closer to normality

Halfdanarson TR, Jatoi A. Curr Oncol Rep 2010;12:247-52.

Aisner J. Am J Health-Syst Pharm 2007;64(Suppl 5):S4-S7

Pros and Cons

Pros Cons

Convenient

Hospitalization not required

Patient autonomy and more in control of care

Less missed work days due to infusion

Patients responsible for adherence

Financial toxicity treatment start delays

Specific administration &storage requirements

Less contact with treating providers

Dillmon MS, et al. J Clin Oncol. 2019; 37:1-12.

Challenges of Oral Oncolytics Adherence (average rate 40-50%)

Complex dosing schedules weeks on/off, certain days of week

Pill burden

Inadequate follow up

Cognitive impairment

Storage and handling

Cost

ASCO Best Practices. J Oncol Pract. 2008; 4(4): 175-77

Mancini R, et al. Practice & Policy, Oncology Journal. 2013; 27 (8).

Challenges of Oral Oncolytics

Work flow

Patients moved out of infusion center

Decreased income for institution if prescriptions sent to other pharmacies

Accessibility/Dispensing

Prior authorizations

Specialty licenses required

Not always stocked

Insurance dictating which pharmacy patient must go to



Challenges of Oral Oncolytics

Interactions/Adjustments

Drug-drug interactions

Absorption interactions

Dose adjustment needs

Side Effects

Can be severe

Patients have less follow up to address toxicities

Financial

High costs

Variable insurance coverage



Financial Toxicity

Patients required to pay upfront vs. going through insurance claims

High out of pocket costs for patients (~25-50% of the total cost!) In 2009, oral oncology medication monthly out-of-

pocket costs averaged $2,942, up 17% from 2008

~10% of patients choose not to fill their initial prescriptions for oral oncolytic due to cost (Avalere Health study)


Mosely WG, Nystrom JS. Community Oncology. 2009; 6:358-61

Orals for Hematologic Malignancies

BTK inhibitors Acalabrutinib Ibrutinib Zanubrutinib

Tyrosine kinase inhibitors Bosutinib Dasatinib Nilotinib Ponatinib Imatinib

Immunomodulators Lenalidomide Thalidomide

Proteasome inhibitor Ixazomib

IDH inhibitors Enasidenib Ivosidenib

PI3K inhibitors Idelalisib

Duvelisib

Copanlisib

FLT3 inhibitors Midostaurin

Gilteritinib

Sorafenib

HDAC inhibitors Panobinostat

Vorinostat

JAK inhibitor Ruxolitinib

Fedratinib

BCL2-inhibitor Venetoclax

https://www.fda.gov

What’s new on the market?

New drugs

2018

• Gilteritinib (Xospata)

• Glasdegib (Daurismo)

• Duvelisib (Copiktra)

• Ivosidenib (Tibsovo)

2019

• Zanubrutinib (Brukinsa)

• Fedratinib (Inrebic)

• Selinexor (Xpovio)

New indications

Acalabrutinib (Calquence)

Ruxolitinib (Jakafi)

Venetoclax (Venclexta)

https://www.fda.gov

Newly Approved Agents

FMS-like receptor tyrosine kinase-3(FLT3) inhibitor

Gilteritinib (Xospata) Date approved: November 28, 2018 [orphan product designation]

Indication: Relapsed, refractory AML with FLT3 mutation as detected by an FDA-approved test

Dose: 120 mg once daily for a minimum of 6 months taken w/ or w/o food

AE: Serious: QTc prolongation, pancreatitis, differentiation syndrome [US

boxed warning]

Common: Elevated LFTs, myalgia, nausea, headache

Drug interactions: Avoid with strong CYP3A4 inhibitors

Clinical Pearls: MOA also has AXL inhibition (may play role in therapeutic resistance)

Differs from midostaurin (Rydapt) monotherapy and refractory setting

Xospata (gilteritinib) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; May 2019.Serious = Grade 3 & 4 toxicity

Common = ≥ 20% incidence

• N=138 adult patients with R/R AML w/ a FLT3 ITD, D835, or I836 mutation

ADMIRAL trial

• Gilteritinib 120 mg daily until unacceptable toxicity or lack of clinical benefit vs. salvage chemotherapy

Intervention• Median follow-up:

4.6 months

• 29 patients achieved CR or CRh (21%, 95% CI: 14.5, 28.8)

Outcomes

Gilteritinib (Xospata)

Perl AE, et al: 2019 AACR Annual Meeting. Abstract CT184. Presented April 2, 2019.

Hedgehog pathway inhibitor

Glasdegib (Daurismo) Date approved: November 21, 2018 [orphan product designation]

Indications: Newly diagnosed AML in patients ≥75 years old or have comorbidities that preclude use of intensive induction chemo

Dose: 100 mg once daily taken w/ or w/o food

AE: Serious: QTc prolongation

Common: Anemia, fatigue, hemorrhage, febrile neutropenia, musculoskeletal pain, nausea, edema, thrombocytopenia, dyspnea, decreased appetite, dysgeusia, mucositis, constipation, and rash

Drug Interactions Strong CYP3A4 inhibitors and QTc prolonging drugs

Clinical Pearls: Approved in combination with low-dose cytarabine

Patients may not donate blood for at least 30 days after last dose

Daurismo (glasdegib) [prescribing information]. New York, NY: Pfizer Labs; November 2018.

Serious = Grade 3 & 4 toxicity


• N=115 patients with newly-diagnosed AML

BRIGHT AML 1003

Study

• Glasdegib 100 mg daily + LDAC 20 mg SC twice daily vs. LDAC alone

Intervention• Median follow-up:

20 months

• Median survival: 8.3 months (95% CI: 4.4, 12.2) vs. 4.3 months (95% CI: 1.9, 5.7) and HR of 0.46 (95% CI: 0.30, 0.71; p=0.0002).

Outcomes

Glasdegib (Daurismo)

Cortes JE, et al. Am J Hematol. 2018;93(11):1301-1310.

Phosphoinositide 3-Kinase (PI3K) inhibitor

Duvelisib (Copiktra) Date approved: September 24, 2018

Indications: CLL/SLL after at least 2 prior therapies

Relapsed/refractory FL after 2 prior systemic therapies

Dose: 25 mg twice daily taken w/ or w/o food

AE: [US Boxed warnings]: Fatal infections (31%), diarrhea (18%), cutaneous reactions

(5%), pneumonitis (5%)

Serious: Hepatotoxicity, neutropenia, embryo-fetal toxicity

Common: Transient lymphocytosis, diarrhea, neutropenia, rash, fatigue, cough, nausea, URI/pneumonia, anemia

Drug Interactions: Avoid CYP3A4 inducers, dose reduce with inhibitors

Acts as CYP3A4 inhibitor monitor for toxicities of drugs that are substrates

Clinical Pearls: Differs from idelalisib (Zydelig) blocks both delta and gamma isoforms of PI3K

PCP pneumonia prophylaxis recommended during treatment, until CD4 count > 200 cells/microliter

Copiktra (duvelisib) [prescribing information]. Needham,

MA: Verastem, Inc; July 2019.

Serious = Grade 3 & 4 toxicity


PI3K inhibitorsDuvelisib (Copiktra) - FL and CLL Idelalisib (Zydelig) - FL and CLLCopanlisib (Aliqopa) - FL

CLL/SLL - NCT02004522 FL - NCT02204982

Patients N=196 patients N=83 patients

Interventions Duvelisib 25 mg twice daily vs. ofatumumab

Duvelisib 25 mg twice daily + rituximab vs. placebo + rituximab

Outcomes • Estimated median PFS: 16.4 months vs. 9.1 months (hazard ratio of 0.40; standard error 0.2)

• ORR: 78% vs. 39% (39% difference, standard error 6.5%)

• ORR: 42% (95% CI: 31, 54), with 41% of patients experiencing partial responses and one patient having a complete response

• 15 (43%) maintained responses for at least 6 months and 6 (17%) maintained responses for at least 12 months

Duvelisib (Copiktra)

Flinn IW, Hillmen P, Montillo M, et al. Blood. 2018 Dec 6;132(23):2446-2455.

https://clinicaltrials.gov/ct2/show/results/NCT02204982

Isocitrate-dehydrogenase type 1 (IDH1) inhibitor

Ivosidenib (Tibsovo) Date approved: July 20, 2018 [orphan product designation] Indications: AML with susceptible IDH1 mutation as detected by FDA

approved test Relapsed/refractory AML As of 2019: Newly-diagnosed AML who are ≥ 75 years old or have

comorbidities that preclude use of intensive induction chemotherapy

Dose: 500 mg once daily taken w/ or w/o food (do NOT administer with a high fat meal)

AE: Serious: QTc prolongation, differentiation syndrome [US Boxed Warning] Common: Fatigue, arthralgia, leukocytosis, electrolytes abnormalities

Drug Interactions: Avoid with CYP3A4 inducers/substrates & QTc prolonging drugs Dose reduce with CYP3A4 inhibitors

Clinical Pearls: Differs from enasidenib (IDH2 inhibitor) Treatment recommended for minimum 6 months to allow for clinical response

Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals; May 2019.Serious = Grade 3 & 4 toxicity


Differentiation Syndrome

Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals; May 2019.

Xospata (gilteritinib) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; May 2019.

Causative agents

• IDH inhibitors (19%), gilteritinib (3%), arsenic trioxide, all-trans retinoic acid

Symptoms

• Fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain, peripheral edema, hypotension, renal dysfunction

Treatment

• Corticosteroids Dexamethasone 10 mg (or equivalent) IV every 12 hours for a minimum of 3 days

• Interrupt treatment w/ offending agent if symptoms for > 48 hrs after starting steroid

Monitoring &Follow up

• Hemodynamic monitoring

• Resume agent when signs/symptoms improve to ≤ grade 2 (mild to moderate)

Ivosidenib (Tibsovo)

• N=28 patients at least 75 years old with one of the following:

• Baseline ECOG status of ≥ 2

• Severe cardiac or pulmonary disease

• Hepatic impairment with bilirubin > 1.5 times the upper limit of normal

• CrCL < 45 mL/min

Study AG120-C-001

• Ivosidenib 500 mg daily

Intervention • Twelve (42.9%) of the 28 achieved CR+CRh (95% CI: 24.5, 62.8)

• 7 (41.2%) of the 17 transfusion-dependent patients achieved transfusion independence lasting at least 8 weeks

Outcomes

https://clinicaltrials.gov/ct2/show/NCT02074839

Bruton’s tyrosine kinase (BTK) inhibitor

Zanubrutinib (Brukinsa) Date approved: November 14, 2019 [orphan product and

breakthrough therapy designation] Indications: MCL after at least one prior therapy Dose: 160 mg twice daily or 320 mg once daily taken w/ or w/o food AE:

Serious: Hemorrhage, infections, cytopenias, secondary primary malignancies, cardiac arrhythmias

Common: Hypertension, decreased neutrophils/platelets/WBC, URI, rash, bruising, diarrhea, cough

Drug Interactions: Modify dose with moderate and strong CYP3A4 inhibitors Avoid CYP3A4 inducers

Clinical Pearls: Selectivity: Acalabrutinib (Calquence) > Zanubrutinib (Brukinsa) >

Ibrutinib (Imbruvica) Less bleeding, atrial fibrillation, and hypertension compared to ibrutinib

Brukinsa (zanubrutinib) [prescribing information]. San Mateo, CA: BeiGene USA Inc; November 2019.Serious = Grade 3 & 4 toxicity


Zanubrutinib (Brukinsa)Phase 2 open-label clinical trial (BGB-3111-206)

Phase 1/2 open label clinical trial (BGB-3111-AU-003)

Patients N=86 patients N=32 patients

Interventions 160 mg twice daily until disease progression or unacceptable toxicity

160 mg twice daily and 320 mg once daily

Outcomes ORR was 84% (95% CI: 74, 91), with a CR rate of 59%(95% CI 48, 70) and a median response duration of 19.5 months (95% CI: 16.6, not estimable)

ORR was 84% (95% CI: 67, 95), with a CR rate of 22% (95% CI: 9, 40) and a median response duration of 18.5 months (95% CI: 12.6, not estimable)

Song Y, et al. Blood. 2018;132(suppl 1):S132.

Tam CS, et al. Blood. 2019;134(11):851-859.

Janus Kinase 2 (JAK-2) inhibitor

Fedratinib (Inrebic) Date approved: August 16, 2019 [orphan drug designation] Indications: Adults with intermediate-2 or high-risk primary or secondary

(post-polycythemia vera or post-essential thrombocythemia) myelofibrosis Dose: 400 mg once daily taken w/ or w/o food (high fat meal reduces

nausea/vomiting) AE:

Serious: anemia, thrombocytopenia, GI toxicity, hepatotoxicity, amylase/lipase elevation, fatal encephalopathy [US Boxed Warning]

Common: diarrhea, nausea, vomiting

Drug Interactions: Avoid w/ strong & moderate CYP3A4 inducers Reduce dose w/ strong CYP3A4 inhibitors Avoid w/ dual CYP3A4 + 2C19 inhibitor

Clinical Pearls: Assess thiamine levels in patients prior to starting and periodically during

treatment Baseline platelet level of 50,000/mm3 required to start treatment Differs from ruxolitinib (Jakafi) JAK-2 only inhibition, more toxicities

Inrebic (fedratinib) [prescribing information]. Summit, NJ; Celgene Corporation; August 2019.Serious = Grade 3 & 4 toxicity


Fedratinib (Inrebic)

• N=289 patients

JAKARTA trial

• Fedratinib 500 mg (N=97) or 400 mg (N=96) once daily for 6 cycles

Intervention

• In 400 mg group (recommended dose):

• 35 (37%) achieved a ≥ 35% reduction in spleen volume

• Median duration of spleen response: 18.2 months

• 40% of patients experienced a ≥ 50% reduction in myelofibrosis-related symptoms

Outcomes

Pardanani A, et al. JAMA Oncol. 2015;1(5):643-651

Nuclear export (XPO1) inhibitor

Selinexor (Xpovio) Date approved: July 3, 2019

Indications: Relapsed/refractory multiple myeloma in combination with dexamethasone

Dose: 80 mg/dose twice weekly on days 1 and 3 each week (in combination with dexamethasone) taken without regard to food

AE: Serious: Hematologic toxicities (thrombocytopenia, neutropenia) GI

toxicity, hyponatremia, infectious, neurological toxicity

Common: Fatigue, nausea (72%), anemia, diarrhea, vomiting, dyspnea, URI

Clinical Pearls: Patients must have received at least 4 prior therapies and disease is

refractory to at least 2 proteasome inhibitors, at least 2 immunomodulators, and an anti-CD38 monoclonal antibody

Antiemetics are recommended prior to and during treatment

Xpovio (selinexor) [prescribing information]. Newton, MA: Karyopharm Therapeutics Inc; July 2019.Serious = Grade 3 & 4 toxicity


Selinexor (Xpovio)

• N=122 patients

STORM trial

• 80 mg in combination with dexamethasone 20 mg on days 1 and 3 of every week

Intervention

• ORR: 25.3% (95% CI: 16.4, 36)• 1 stringent CR

• No CR

• 4 very good partial responses

• 16 partial responses

• Median time to first response: 4 weeks (range: 1 to 10 weeks)

• Median response duration: 3.8 months (95% CI: 2.3, not estimable)

Outcomes

Chari A, et al. N Engl J Med. 2019;381(8):727-738.

New Indications

Drug Previous Indications New Indications

Acalabrutinib(Calquence)

Patients with MCL who have received at

least one prior therapy

• CLL and SLL

Ruxolitinib(Jakafi)

Intermediate or high-risk myelofibrosis

• Steroid-refractory acute graft-versus-host disease in adults and pediatrics 12 years and older

Venetoclax(Venclexta)

Patients with CLL and SLL with 17p

deletion who have received at least one

prior therapy

• Newly-diagnosed AML in adults 75 years or older, or have comorbidities that preclude use of intensive induction chemotherapy (in combination with azacitidineor decitabine or low-dose cytarabine)

• Previously untreated CLL and SLL

https://www.fda.gov/drugs/resources-information-approved-drugs/hematologyoncology-cancer-approvals-safety-notifications

Acalabrutinib (Calquence) MOA: BTK inhibitor

Dose: 100 mg every 12 hours

Labeling Updates for CLL/SLL based on two randomized controlled clinical trials

ELEVATE-TN ASCEND

N= 535 patients N=310 patients

3 arms: acalabrutinib monotherapy, acalabrutinib plus obinutuzumab, or obinutuzumab plus chlorambucil

Treatment arms: acalabrutinib or investigator’s choice (idelalisib plus a rituximab product, or bendamustineplus a rituximab product)

Outcomes:• Median follow up: 28.3 months• PFS was significantly improved in acalabrutinib arms• Compared to the obinutuzumab plus chlorambucil

arm, the hazard ratio (HR) for PFS was 0.10 (95% CI: 0.06, 0.17; p < 0.0001) with acalabrutinib plus obinutuzumab and 0.20 (95% CI: 0.13, 0.30; p < 0.0001) with single agent acalabrutinib.

Outcomes:• Median follow-up: 16.1 months• PFS was significantly longer in the

acalabrutinib arm compared to the investigator’s choice arm (HR 0.31; 95% CI, 0.20, 0.49; p < 0.0001)

Sharman JP, et al. Blood. 2019;134(Supplement_1):31.

Ghia P, et al. Presented at: 2019 European Hematology Association Congress; June 13-16, 2019; Amsterdam, Netherlands. Abstract LB2606

Ruxolitinib (Jakafi) MOA: JAK1/2 selective inhibitor Dose: 5 mg twice daily may increase to 10 mg twice daily after 3 days Labeling updates for GVHD based on Study INCB 18424-271


Study INCB 18424-271 (NCT02953678)

Patients N=49 patients with steroid-refractory acute GVHD Grades 2 to 4 occurring after allogeneic HSCT

Intervention 5 mg twice daily (could be increased to 10 mg twice daily after 3 days in the absence of toxicity) + steroids

Outcomes • Day-28 ORR was 100% for Grade 2 GVHD, 40.7% for Grade 3 GVHD, and 44.4% for Grade 4 GVHD

• Median response duration: 16 days (95% CI: 9, 83)

• Median time from day-28 response to either death or need for new therapy for acute GVHD: 173 days (95% CI 66, not estimable)


MOA: BCL-2 inhibitor

Dose: Varies based on indication Usually includes ramp-up schedule to avoid tumor lysis syndrome


CLL14 trial

• N=432 patients with previously untreated CLL and SLL

Interventions

• Venetoclax in combination with obinutuzumab(VEN+G) vs. obinutuzumab in combination with chlorambucil (GClb)

Outcomes

• Median follow up: 28 months

• Improvement in PFS for patients who received VEN+G (HR 0.33; 95% CI: 0.22, 0.51; p<0.0001)

• Median PFS was not reached in either arm

• ORR: 85% in VEN+G arm compared to 71% in GClb arm, p=0.0007

Fischer K, et al. N Engl J Med 2019; 380:2225-2236

Labeling update for previously untreated CLL and SLL based on the CLL14 trial

Venetoclax (Venclexta) Labeling update for newly-diagnosed AML in combination with

azacitidine, decitabine or low- dose cytarabine in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemo based on phase Ib clinical trial

Phase Ib clinical trial

• N=145 patients

Interventions

• Venetoclax 400, 800, or 1200 mg daily in combination with either decitabine or azacitidine

Outcomes

• Complete remission (CR) + CR within incomplete count recovery (CRi): 67%

• Median duration of response: 11.3 months

• Overall survival: 17.5 months (ongoing)

DiNardo C, et al. Blood. 2019 Jan 3;133(1):7-17.

Role of the Pharmacist

Keys to a Successful Oral Oncolytic Program

1. Multidisciplinary approach

2. Assign responsibilities

3. Collaborate with specialty pharmacy

4. Provide financial advocacy services

5. Develop a robust patient education program

6. Put in place effective processes for monitoring adherence and toxicity

7. Maximize the use of technology

Association of Community Cancer Centers. Steps to Success: Implementing Oral Oncolytics. Retrieved

from: https://www.accc-cancer.org/docs/projects/resources/pdf/implementing-oral-oncolytics-final

Pharmacist’s Role

Uniquely positioned to enhance care for cancer patients who receive oral oncolytic therapy through:

Medication management

Patient education

Self-care management

Quality and safety management

Dispensing assistance


Role of the Pharmacist

Prescribing

Education

Dispensing & Distribution

Monitoring & Follow Up


Prescribing Patient consent should be obtained

Provide comprehensive review of new oral oncolytics and determine place in therapy via interprofessional formulary committee

Creation of oral oncolytic templates for electronic prescribing that include required components, standard supportive care, & monitoring

Perform comprehensive medication review at the time of prescription

Oncology team should communicate the intent of oral oncolytic therapy, pertinent drug–drug interactions, and potential implications for the patient’s comorbidities and management strategies to the patient’s PCP


Education Involvement in the development/endorsement of

standardized education materials

A separate education visit—in person or over the phone—should occur after the oncologist’s initial prescribing visit and before the start of oral oncolytic therapy to supplement and reiterate the information provided during the oncologist visit

Education should be comprehensive and focus on patient self-care management of adverse effects and the importance of adherence

An assessment of patient knowledge, confidence to manage adverse effects, and need for follow-up should occur during the education session


Dispensing/Distribution Dedicated medication assistance team prospectively screen

& provide financial support

The dispensing pharmacy should have access to necessary information for safe filling (laboratory values and progress notes)

Dedicated liaison available for the clinic to provide information on financial toxicities, refills, medication adherence, and any identified medication adverse effects

Specialty pharmacists and oncology pharmacy organizations should partner to promote the education of oncology pharmacists and optimize oncology patient care


Name of Organization/Study Tool for Oral Oncolytic Dispensing

National Community Oncology Dispensing Association (ncoda.org)

Oral chemotherapy education: • Cost avoidance and waste tracker• Patient satisfaction survey• Positive quality interventions

Chemocare.com Web resource for drug and side-effect information, wellness information, and other

Hematology Oncology Pharmacy Association Oral Chemotherapy resources (hoparx.org)

Tools and resources for:• Best practices, therapy initiation, financial resources,

education, monitoring, symptoms, and adherence

Cancer Care Ontario Drug and safety administration:• Recommended criteria of a preprinted order: oral

chemotherapy take-home prescriptions • Clinical verification of cancer drug prescriptions checklist:

cancer centers and specialty pharmacies

Michigan Oncology Quality Consortium

Oral oncolytics resource guide:• Therapy initiation resources, oral oncolytic checklist,

medication reconciliation process summary, oral oncolytic initiation template, initial dose mailer, calendar, education and monitoring

Oncology Nursing Society Checklist for a new start oral chemotherapy Dillmon MS, et al. J Clin Oncol. 2019; 37:1-12.

Monitoring/Follow Up Involvement in creation of monitoring and follow-up materials

Initial monitoring of symptoms & adherence should occur 7 -14 days after start

Ongoing monitoring of symptoms & adherence should occur at each clinical encounter, at least before each refill

Medication reconciliation should occur at each assessment point

Adherence assessment should be user friendly, reliable, cost effective, and practical

Collaborative practice agreement for laboratory and symptom monitoring, should exist where pharmacists are part of the interdisciplinary oncology care team

Ongoing communication


Practice Management

Pharmacist involvement in an oral oncolytic program

Perform baseline gap assessment to assess areas for improvement and baseline performance on oral oncolytic quality measures

Assess the following for continuous quality improvement: Pre- and post-financial, clinical quality measures, including interprofessional and patient experience


Example Workflow


Inpatient Setting Drug selection

Inter-professional interactions in formulary committees Evaluate clinical data, national guidelines, comparison of same-

class agents/biosimilars, financial toxicity, clinical cancer pathways

Standardize the ordering process Safety checks Symptom management protocols Proper dosing, dosage forms, lab testing

Identification of oral chemotherapy toxicities Is the oral oncolytic causing the toxicities that led to admission? Prescriber education


Outpatient Setting

Comprehensive medication reviews Drug-drug interactions Drug-food interactions Assess comorbidities Dosage adjustments Dosing schedules Counseling

Financial assistance Collaborating with insurance companies Enrolling patients in patient assistance programs


Conclusions

Oral oncolytic therapy development and prescribing is continuing to rise

Oral oncolytic therapy is associated with challenges in adherence, safety, and costs

Pharmacists in all settings are uniquely positioned to mitigate the risks associated with oral oncolytic therapy

Test Your Knowledge

T/F? Oral oncolytics comprise ~5% of the oncology pipeline

T/F? Venetoclax (Venclexta) was recently FDA approved for chronic lymphocytic leukemia

T/F? Selinexor (Xpovio) is an oral nuclear export inhibitor indicated for the treatment of refractory multiple myeloma in combination with dexamethasone

False

True

True

References Macker E, Segal EM, Muluneh B, et al. 2018 Hematology/Oncology Pharmacist Association Best Practices for the

Management of Oral Oncolytic Therapy: Pharmacy Practice Standard. J Clin Oncol. 2018; 15(4):e346-355. Dillmon MS, Kennedy EB, Anderson MK, et al. Patient-centered standards for medically integrated

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Macker E, Segal EM, Muluneh B, et al J Clin Oncol. 2018;

15(4):e346-355.

Update on Oral Oncolytics: A Focus on Hematology Drugs

Presenter: Monica Tadros, Pharm.D., BCPS

Miami Cancer Institute, Baptist Health South Florida

[email protected]