Trend Report for Oncology Medications: Where Oncologic Pharmaceuticals are Going from a Bird’s Eye View Provi vidence Ala laska Medic ical l Ce Center PGY2 Oncology Resident Kait ite Kammers, , Pharm rmD October 20, 2018
Disclosures Presenter has no financial relationship relevant to this activity.
Objectives • Describe recent trends in oncology medications • Explain the role pharmacy can play in the management of new targeted small molecules and immunotherapies • Recognize the challenges, advantages, and role of biosimilars
Pre-Test (1) All of the following are considered recent trends in oncology, except : A. Biosimilars B. Hormonal-antineoplastic conjugates C. Targeted oral therapy D. Immunotherapy (2) The prim rimary sid ide e effec ect related to CAR T-Cell therapy and T-Cell engagers that may require pharmacy management is: A. Erythematous rash B. Hypertension C. Renal dysfunction D. Cytokine release syndrome (3) Poor provider and patient education on the safety and efficacy of biosimilars is a primary cause for the poor uptake of biosimilars in the United States. A. True B. False
Outline • Overview of trends in the past 12 – 24 months • Targeted therapy • Immunotherapy • Biosimilars • Impact for pharmacy
Trends to Watch… • Targeted th therapie ies • Based on predictive biomarkers • Push toward oral agents • Im Immunotherapy • Check point inhibitors • Adaptive cell therapy (CAR T) • Bi-specific/ simultaneous multiple interaction T-cell engagers • Therapeutic vaccines • Bio iosim imil ilars • Promising for decreased cost of care • Many set backs and concerns
Targeted Therapy • Interfere with specific molecules that are involved in the growth, progression, and sp spread of cancer • Act on sp specifically ly ch chosen tar argets vs. all rapidly dividing cells (i.e traditional antineoplastic chemotherapy) • Can be monoclonal l an antib ibodie ies (mAbs) or sm small l mole lecule les • mAbs targets on outside of cell • Small molecules targets on inside of cell • Common targets are protein ins/receptors th that ar are dif ifferent in in mali alignant compared to benign cells: • Proteins in higher quantities than normal • Mutated proteins • Proteins not in normally functioning cells
Type of f Target Examples SERMs, Estrogen antagonists, Androgen Horm rmones antagonists BRAF/MEK inhibitors, BCR-abl inhibitors, EGFR Sig Signal l tr transductio ion inhibitors in inhib ibit itors Apoptosis is ind inducers Proteasome inhibitors, PARP inhibitors, BCL-2 inhibitors VEGF inhibitors Angio iogenesis is in inhib ibit itors PD-1 inhibitors, CTLA-4 inhibitors, CD20 inhibitors Im Immunotherapie ies Brentuximab-vedotin, trastuzumab emtansine “Pay - load” toxic molecules Ess ssentia iall lly 4 4 end effects: apoptosis, anti-proliferation, anti-angiogenisis, and immuno-stimulation
Ess ssentia iall lly 4 4 end effects: • apoptosis • anti-proliferation • anti-angiogenesis • immuno-stimulatio n
New(er) Targeted Therapies • BCL-2 inhibitors • PARP inhibitors • EGFR inhibitors • IDH1/2 inhibitors • CDK inhibitors • Immunotherapy
BCL-2 Inhibitors Drug rugs venetoclax MOA Inhibition on BCL-2 leads to direct apo apoptosis itors ( ↓ / ↑ conc.), live vaccines (diminished effect) Drug rug CYP3A4 ind inducers/in inhibit Interactio In ions Adv dverse Tum umor or lysis is syndrome (TL (TLS)(13% during first 3 weeks), pa pancytopenia ia, increased LFTs, Effects skin rashes, diarrhea/ constipation, nausea and vomiting (10-30%) • Obtain 17p Man anagement t p de dele letio ion status for CLL prior to initiation or relapse • Administer hydr Pea earls ls dratio ion and and hyperu ruric icemic ic the therapy as as pr pre-meds based on TLS risk • May need to admit patient during initiation • May administer G-CSF to reduce risk of febrile neutropenia • Dose reductions for TLS and neutropenia • Spe pecialty pha pharm rmacy med edic icatio ion
PARP inhibitors Drug rugs olaparib, rucaparib, niraparib MOA Inhibition of PARP leads to accumulation of DNA errors and apo apoptosis itors ( ↓ / ↑ conc.), CYP1A2 substrates ( rucaparib , inhibitor) Drug rug CYP3A4 ind nducers/in inhibit Interactio In ions Adv dverse Effects Pan ancytopenia ia, mus uscle le fatig igue/pain, fatigue, nausea & vomiting, increased serum creatinine, <1% risk for MDS/AML • Obtain BRCA-mutatio Man anagement t ion status (somatic vs. germline) prior to initiation, except Pea earls ls niraparib • Monitor CBC at baseline, then monthly • Dose adjustments for renal impairment • Spe pecialty pha pharm rmacy med edic icatio ion
EGFR inhibitors erlotinib*, afatinib^, gefitinib*^ † , osi Drug rugs osimertin inib ib^, cetuximab, panitumumab, necitumomab MOA Inhibition of EGFR leads to de decreased growth and and pr prol olif iferatio ion itors* ( ↓ / ↑ conc.), BCRP/ABCG2 inducers/inhibitors^ ( ↓ / ↑ Drug rug CYP3A4 ind inducers/in inhibit conc.), CYP2D6 inducers/inhibitors ( ↓ / ↑ conc.) † In Interactio ions Adv dverse Effects Skin cha changes (~ 1 week post-initiation), di diarr rrhea, increased LFTs, conjunctivitis, hypomagnesaemia, pneumonitis • Obtain EGFR mut Man anagement t utatio ion status prior to initiation for NSCLC • Obtain KR Pea earls ls KRAS mut utatio ion status for cetuximab & panitumumab in colorectal • Loperamide for mild-moderate diarrhea • Topical or oral corticosteroids/ antibiotics for dermatologic toxicities • Avoid sunlight, wear sunscreen • Dose reductions for dermatologic, GI, pulmonary, and ocular toxicities • Spe pecialty pha pharm rmacy for or osim simertin inib ib
IDH1 /2 Inhibitors Drug rugs ivosidenib (IDH1), enasidenib (IDH2) MOA Inhibition of mutant IDH leads to restored “normal” differentiation of cells and de decreased pr prol oliferatio ion of of mal alig ignant ce cell lls itors ( ↓ / ↑ conc.), ABCG1 inducers/inhibitors ( ↓ / ↑ conc.), + Drug rug CYP3A4 ind nducers/in inhibit In Interactio ions many more minor enzymes for enasidenib Adv dverse Effects Dif ifferentia iatio ion synd ndrome (during first 3 months), TL TLS, QT T pr prol olongatio ion, nausea & vomiting, diarrhea, increased LFTs, increased SCr, arthralgia/myalgia • Obtain ID Man anagement t IDH mut utatio ion status prior to initiation, retest at relapse as mutations Pea earls ls can occur early or later in disease process • Dexamethasone IV and hemodynamic monitoring of differentiation syndrome, high dose hydroxyurea for leukocytosis • Dose reductions for hepatotoxicity • Spe pecialty pha pharm rmacy med edic icatio ion
CDK Inhibitors Drug rugs palbociclib, ribociclib, abemaciclib MOA Inhibition of CDK leads to de decreased growth and and pr prol oliferatio ion itors ( ↓ / ↑ conc.), live vaccines (diminished effect) Drug rug CYP3A4 ind inducers/in inhibit Interactio In ions Adv dverse Effects Neu eutropenia ia, alopecia, inc ncreased LFT FTs, dia diarrhea, nausea and vomiting, QT prolongation (ribociclib) • Obtain es Man anagement t estrogen rec eceptor r and HER ER2 rec eceptor r status prior to initiation • Concomitantly given with ar Pea earls ls arom omatase inh nhib ibit itors • Dose reductions for hepatotoxicity and hematologic toxicities • Dose reductions for renal impairment with ribociclib • Spe pecialty pha pharm rmacy med edic icatio ion
Side Effect Themes • Diarrhea • Liver problems (hepatitis, elevated LFTs) • Skin problems (acneiform rash, dry skin, nail changes, hair depigmentation) • Associated with better outcomes, common with EGFR inhibitors • Blood clots • Poor wound healing • Common with VEGF inhibitors • High blood pressure • Common with VEGF inhibitors
Pharmacy Management of Targeted Therapy 1. Adherence • Many of targeted therapies are self-administered 2. Side effect management and monitoring 3. Patient education 4. Drug interaction monitoring/checking 5. Coordination with specialty pharmacies, if needed 6. Patient support programs through pharmaceutical company 7. Locating samples for bridging
Immunotherapy • “Cancer’s penicillin moment” – Ir Ira Mellm llman • Both from a treatment breakthrough and challenges posed perspective • Help lps the im immune system attack cancer cells lls • Remove “brakes” • Increase recognition • Flag cancer cells • Boost response
Types of FDA approved Immunotherapy Ch Check-Poin int In Inhib ibit itors • In Increase T-cell ll activ ivit ity CAR T-Cell lls • ↑ T -cell activation • Genetic icall lly y engin ineered T-cell lls to • prevent T-cell from being tar arget can ancerous cell lls turned off • Limited, but growing use • Wide-spread use in many types of cancer T-Cell l Engagers • Lin Link T-cell lls to cancerous cell lls Therapeutic vaccin ines • Limited Use • Im Immuno-stim imula lant • Limited use
Recommend
More recommend
