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1-11-2020

Update on Oral Oncolytics: A Focus on Hematology Drugs

Monica Tadros Miami Cancer Institute, [email protected]

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

This Conference Lecture -- Open Access is brought to you for free and open access by Scholarly Commons @ Baptist Health South Florida. It has been accepted for inclusion in All Publications by an authorized administrator of Scholarly Commons @ Baptist Health South Florida. For more information, please contact [email protected]. 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  CLL: Chronic lymphocytic leukemia  BTK: Bruton’s tyrosine kinase  SLL: Small lymphocytic  IDH: Isocitrate dehydrogenase  FL: Follicular lymphoma  PI3K: Phosphoinositide 3-kinase  URI: Upper respiratory infection  FLT3: FMS-like -3  PCP: Pneumocystis pneumonia; Primary care  HDAC: Histone deacetylase physician  JAK:  ORR: Overall response rate  BCL-2: B-cell lymphoma 2  CI: Confidence interval  AML:  ECOG: Eastern Cooperative Oncology Group  MOA: Mechanism of action  MCL: Mantle cell lymphoma  FDA: Food and Drug Administration  AE: Adverse effects  LFT: Liver function tests  GI: Gastrointestinal  CR: Complete response / remission  PFS: Progression free survival  CRh: Complete response with partial  GVHD: Graft-versus-host disease hematologic recovery  HSCT: Hematopoietic stem cell transplant  CRi: Complete remission with incomplete  HR: Hazard ratio count recovery  OS: Overall survival  LDAC: Low dose cytarabine  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 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 Patients responsible for adherence Hospitalization not required Financial toxicity  treatment Patient autonomy and more in start delays control of care Specific administration & Less missed work days due to storage requirements infusion 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

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

 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

ASCO Best Practices. J Oncol Pract. 2008; 4(4): 175-77 Mancini R, et al. Practice & Policy, Oncology Journal. 2013; 27 (8). 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 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)

Mancini R, et al. Practice & Policy, Oncology Journal. 2013; 27 (8). Mosely WG, Nystrom JS. Community Oncology. 2009; 6:358-61 Orals for Hematologic Malignancies  BTK inhibitors  PI3K inhibitors

 Idelalisib   Duvelisib   Copanlisib  Tyrosine kinase inhibitors  FLT3 inhibitors   HDAC inhibitors

 Immunomodulators  Panobinostat

 Lenalidomide  Vorinostat  Thalidomide  JAK inhibitor  Proteasome inhibitor   Ixazomib   IDH inhibitors  BCL2-inhibitor  https://www.fda.gov What’s new on the market?

 New drugs  New indications

 2018  Acalabrutinib (Calquence)

• Gilteritinib (Xospata)  Ruxolitinib (Jakafi)

• (Daurismo)  Venetoclax (Venclexta) • Duvelisib (Copiktra) • Ivosidenib (Tibsovo)

 2019 • Zanubrutinib (Brukinsa) • Fedratinib (Inrebic) • Selinexor (Xpovio)

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

Serious = Grade 3 & 4 toxicity Common = ≥ 20% incidence Xospata (gilteritinib) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; May 2019. Gilteritinib (Xospata)

Intervention • N=138 adult • Median follow-up: patients with R/R • Gilteritinib 120 mg 4.6 months AML w/ a FLT3 ITD, daily until • 29 patients D835, or I836 unacceptable achieved CR or mutation toxicity or lack of CRh (21%, 95% CI: clinical benefit vs. 14.5, 28.8) ADMIRAL salvage trial chemotherapy Outcomes

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 Serious = Grade 3 & 4 toxicity Common = ≥ 20% incidence Daurismo (glasdegib) [prescribing information]. New York, NY: Pfizer Labs; November 2018. Glasdegib (Daurismo)

• Median follow-up: 20 months • N=115 patients Intervention • Median survival: with newly- 8.3 months (95% diagnosed AML • Glasdegib 100 mg daily + LDAC CI: 4.4, 12.2) vs. 4.3 months (95% CI: 20 mg SC twice 1.9, 5.7) and HR of BRIGHT daily vs. LDAC 0.46 (95% CI: 0.30, AML 1003 alone 0.71; p=0.0002). Study Outcomes

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: PI3K inhibitors Duvelisib (Copiktra) - FL and CLL  CLL/SLL after at least 2 prior therapies Idelalisib (Zydelig) - FL and CLL  Relapsed/refractory FL after 2 prior systemic therapies Copanlisib (Aliqopa) - FL  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 Serious = Grade 3 & 4 toxicity Copiktra (duvelisib) [prescribing information]. Needham, Common = ≥ 20% incidence MA: Verastem, Inc; July 2019. Duvelisib (Copiktra)

CLL/SLL - NCT02004522 FL - NCT02204982 Patients N=196 patients N=83 patients Interventions Duvelisib 25 mg twice daily Duvelisib 25 mg twice daily + vs. vs. placebo + rituximab Outcomes • Estimated median PFS: • ORR: 42% (95% CI: 31, 54), with 16.4 months vs. 9.1 41% of patients experiencing months (hazard ratio of partial responses and one 0.40; standard error 0.2) patient having a complete response • ORR: 78% vs. 39% (39% • 15 (43%) maintained difference, standard error responses for at least 6 6.5%) months and 6 (17%) maintained responses for at least 12 months

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

Serious = Grade 3 & 4 toxicity Common = ≥ 20% incidence Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals; May 2019. Differentiation Syndrome

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

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

• Corticosteroids  Dexamethasone 10 mg (or equivalent) IV every 12 hours for a minimum of 3 days Treatment • Interrupt treatment w/ offending agent if symptoms for > 48 hrs after starting steroid

• Hemodynamic monitoring Monitoring • Resume agent when signs/symptoms improve to ≤ grade 2 (mild to moderate) &Follow up Xospata (gilteritinib) [prescribing information]. Northbrook, IL: Astellas Pharma US, Inc; May 2019. Tibsovo (ivosidenib) [prescribing information]. Cambridge, MA: Agios Pharmaceuticals; May 2019. Ivosidenib (Tibsovo)

• N=28 patients at least 75 years old with one of the following: Intervention • Twelve (42.9%) of the 28 • Baseline ECOG status achieved CR+CRh (95% CI: of ≥ 2 24.5, 62.8) • Severe cardiac or • Ivosidenib 500 pulmonary disease mg daily • 7 (41.2%) of the 17 • Hepatic impairment transfusion-dependent with bilirubin > 1.5 patients achieved times the upper limit transfusion independence of normal lasting at least 8 weeks • CrCL < 45 mL/min Outcomes

Study AG120-C- 001

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

Serious = Grade 3 & 4 toxicity Common = ≥ 20% incidence Brukinsa (zanubrutinib) [prescribing information]. San Mateo, CA: BeiGene USA Inc; November 2019. Zanubrutinib (Brukinsa)

Phase 2 open-label clinical Phase 1/2 open label trial (BGB-3111-206) (BGB-3111-AU-003) Patients N=86 patients N=32 patients

Interventions 160 mg twice daily until 160 mg twice daily and 320 mg disease progression or once daily unacceptable toxicity

Outcomes ORR was 84% (95% CI: 74, ORR was 84% (95% CI: 67, 95), with 91), with a CR rate of 59% a CR rate of 22% (95% CI: 9, 40) and (95% CI 48, 70) and a median a median response duration of 18.5 response duration of 19.5 months (95% CI: 12.6, not months (95% CI: 16.6, not estimable) 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 3  Baseline platelet level of 50,000/mm required to start treatment  Differs from ruxolitinib (Jakafi)  JAK-2 only inhibition, more toxicities

Serious = Grade 3 & 4 toxicity Inrebic (fedratinib) [prescribing information]. Summit, NJ; Celgene Corporation; August 2019. Common = ≥ 20% incidence Fedratinib (Inrebic)

• In 400 mg group (recommended dose): Intervention • 35 (37%) achieved a ≥ 35% reduction in spleen • N=289 volume patients • Fedratinib 500 mg (N=97) or • Median duration of spleen 400 mg (N=96) response: 18.2 months once daily for 6 • 40% of patients cycles experienced a ≥ 50% JAKARTA trial 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

Serious = Grade 3 & 4 toxicity Xpovio (selinexor) [prescribing information]. Newton, MA: Karyopharm Therapeutics Inc; July 2019. Common = ≥ 20% incidence Selinexor (Xpovio)

• ORR: 25.3% (95% CI: 16.4, 36) • 1 stringent CR Intervention • No CR • N=122 • 4 very good partial patients • 80 mg in responses combination with • 16 partial responses dexamethasone 20 • Median time to first mg on days 1 and response: 4 weeks 3 of every week (range: 1 to 10 weeks) • Median response STORM trial 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 Patients with MCL • CLL and SLL (Calquence) who have received at least one prior therapy

Ruxolitinib Intermediate or high- • Steroid-refractory acute graft- (Jakafi) risk myelofibrosis versus-host disease in adults and pediatrics 12 years and older

Venetoclax Patients with CLL and • Newly-diagnosed AML in adults 75 (Venclexta) SLL with 17p years or older, or have deletion who have comorbidities that preclude use of received at least one intensive induction chemotherapy prior therapy (in combination with azacitidine or 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 Treatment arms: acalabrutinib or , or obinutuzumab plus chlorambucil investigator’s choice (idelalisib plus a rituximab product, or bendamustine plus a rituximab product) Outcomes: Outcomes: • Median follow up: 28.3 months • Median follow-up: 16.1 months • PFS was significantly improved in acalabrutinib arms • PFS was significantly longer in the • Compared to the obinutuzumab plus chlorambucil acalabrutinib arm compared to arm, the hazard ratio (HR) for PFS was 0.10 (95% CI: the investigator’s choice arm (HR 0.06, 0.17; p < 0.0001) with acalabrutinib plus 0.31; 95% CI, 0.20, 0.49; p < obinutuzumab and 0.20 (95% CI: 0.13, 0.30; p < 0.0001) 0.0001) with single agent acalabrutinib.

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)

https://clinicaltrials.gov/ct2/show/NCT02970318 Venetoclax (Venclexta)

 MOA: BCL-2 inhibitor  Dose: Varies based on indication

 Usually includes ramp-up schedule to avoid tumor lysis syndrome Venetoclax (Venclexta)

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

CLL14 trial Interventions Outcomes • N=432 patients with • Venetoclax in • Median follow up: 28 previously untreated combination with months CLL and SLL obinutuzumab • Improvement in PFS (VEN+G) vs. for patients who obinutuzumab in received VEN+G (HR combination with 0.33; 95% CI: 0.22, chlorambucil (GClb) 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 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 Interventions Outcomes trial • N=145 patients • Venetoclax 400, 800, • Complete remission or 1200 mg daily in (CR) + CR within combination with incomplete count either decitabine or recovery (CRi): 67% azacitidine • 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

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

Prescribing

Education

Dispensing & Distribution

Monitoring & Follow Up

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

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

Macker E, et al. J Clin Oncol. 2018; 15(4):e346-355. Name of Organization/Study Tool for Oral Oncolytic Dispensing National Community Oncology Oral chemotherapy education: Dispensing Association • Cost avoidance and waste tracker (ncoda.org) • Patient satisfaction survey • Positive quality interventions Chemocare.com Web resource for drug and side-effect information, wellness information, and other Hematology Oncology Pharmacy Tools and resources for: Association Oral Chemotherapy • Best practices, therapy initiation, financial resources, resources education, monitoring, symptoms, and adherence (hoparx.org) 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 Oral oncolytics resource guide: Consortium • 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

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

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

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

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

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

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

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

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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]