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3/15/16
1
IMPROVING ADHERENCE AND OPTIMIZING
OUTCOMES WITH OUR NEWEST DRUGS
Ferowsi Pecoraro, PharmD, BCOP Oncology Pharmacist Specialist CHI Franciscan Health March 11, 2016
LEARNING OBJECTIVES
1. Discuss new agents, including administration and monitoring considerations
2. Describe new indications for current therapies, including administration and monitoring considerations
3. Identify treatment-specific challenges to adherence and achieving optimal outcomes and discuss strategies to overcome poor adherence and suboptimal outcomes
WHAT’S NEW?
3/15/16
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IV MEDICATIONS
Elotuzumab (Empliciti™) **New Mechanism**
Necitumumab (Portrazza™)
Daratumumab (Darzalex™)
Irinotecan liposome (Onivyde™)
Trabectedin (Yondelis®)
ORAL MEDICATIONS
Alectinib (Alecensa®)
Ixazomib (Ninlaro®) **1st oral proteasome inhibitor**
Osimertinib (Tagrisso™)
Cobimetinib (Cotellic™)
Trifluridine/tipiracil (Lonsurf®)
Sonidegib (Odomzo®)
Panobinostat (Farydak®)
INDICATIONS
Multiple myeloma – 4
Pancreatic cancer
Non-small cell lung cancer – 3
Melanoma
Basal cell carcinoma
Sarcoma – soft tissue sarcoma, liposarcoma, leiomyosarcoma
Colorectal cancer
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ALECTINIB (ALECENSA®) Class: Kinase inhibitor
Indication: ALK(+) metastatic NSCLC who have progressed on or did not tolerate Crizotinib
Dose/Administration: 600mg PO BID with food until disease progression or unacceptable toxicity
Common side effects: Fatigue, constipation, edema, myalgia, vomiting
Monitoring: LFTs (hepatic panel) every 2 weeks during the first 2 months, then periodically CPK every 2 weeks during the first 1 month, then as clinically indicated if patient reports muscle pain,
tenderness, weakness HR (assess for bradycardia) Dyspnea or chest pain that may indicate PE, interstitial lung disease, pneumonitis
ALECTINIB (ALECENSA®)
Improving adherence: Education on taking medication with food Appropriate antiemetics if patient experiences nausea +/- vomiting Education on avoiding excessive exposure to sunlight and skin protection
Optimizing outcomes: Education on importance of recommended lab monitoring
ELOTUZUMAB (EMPLICITI™)
Class: Monoclonal antibody targeting Signaling Lymphocyte Activation Molecule Family 7 (SLAMF7) – New mechanism
Indication: Multiple myeloma who have received 1-3 prior therapies; in combination with Lenalidomide and Dexamethasone
Dose/Administration: 10mg/kg IV weekly for Cycle 1 and 2, then every 2 weeks until disease progression or unacceptable toxicity; infusions are titrated – Cycle 1 Doses 1 and 2, Cycle 4 up to max 5mL/min Pre-medications: Dexamethasone, Diphenhydramine 25-50mg IV, Ranitidine 50mg IV or equivalent,
Acetaminophen 650-1000mg PO 45-90 min prior to infusion Dexamethasone: 8mg IV 45-90 min prior to infusion and 28mg PO 3-24 hr prior on weeks with
Elotuzumab; 40mg PO on weeks without Elotuzumab Lenalidomide: 25mg PO daily on Days 1-21
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ELOTUZUMAB (EMPLICITI™)
ELOTUZUMAB (EMPLICITI™) Common side effects: Fatigue, diarrhea, constipation, pyrexia, cough, peripheral neuropathy, nasopharyngitis, upper respiratory tract infection, decreased appetite, pneumonia
Monitoring: Infusion reactions Temperature, signs of infection LFTs Providers – potential for new primary malignancy, appropriate assessment of lab results that indicate
response (interfere with assays to monitor M protein)
Improving adherence: Barriers – complicated regimen Reinforce and provide tools to keep track of treatment schedule – detailed calendar
Optimizing outcomes: Follow pre-medication recommendations
NECITUMUMAB (PORTRAZZA™) Class: EGFR inhibitor
Indication: 1st-line in metastatic squamous NSCLC; in combination with Cisplatin and Gemcitabine
Dose/Administration: 800mg IV over 60 min on Days 1 and 8 of each 21-day cycle; continue until disease progression or unacceptable toxicity (max 6 cycles of Cisplatin/Gemcitabine) Pre-medications: Diphenhydramine or equivalent if experienced Grade 1 or 2 infusion-related
reaction. After 2nd Grade 1 or 2 reaction, pre-medicate with Diphenhydramine, Acetaminophen, Dexamethasone (or equivalents) prior to each treatment.
Common side effects: Rash, hypomagnesemia
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NECITUMUMAB (PORTRAZZA™) Monitoring: Electrolytes (Mg, K, Ca), symptoms indicating low Mg; low Mg may be increased when combined with
Cisplatin Replace when appropriate Continue monitoring for at least 8 weeks after Necitumumab
Rash Infusion related reactions DVT/PE
Improving adherence: Education on limiting sun exposure; addressing dermatologic toxicities Appropriate antiemetics during concurrent Cisplatin/Gemcitabine
Optimizing outcomes: Education on importance of electrolyte monitoring and replacement Initiating pre-medications if infusion-related reactions occur
IXAZOMIB (NINLARO®) Class: Proteasome inhibitor – 1st oral in class
Indication: Multiple myeloma who have received at least 1 prior therapy; in combination with Lenalidomide and Dexamethasone
Dose/Administration: 4mg PO on Days 1, 8, and 15 of 28-day cycle on an empty stomach; continue until disease progression or unacceptable toxicity Lenalidomide: 25mg PO on Days 1-21 Dexamethasone: 40mg PO on Days 1, 8, 15, and 22 of 28-day cycle
Common side effects: Diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, vomiting, peripheral edema, back pain
IXAZOMIB (NINLARO®) Monitoring: Platelets, LFTs GI symptoms Peripheral neuropathy Rash Fluid retention
Improving adherence: Appropriate antiemetics if patient experiences nausea +/- vomiting Ensure appropriate doses in patients with renal or hepatic impairment
Optimizing outcomes:
Education on taking medication on empty stomach
Request pharmacist review for potential drug interactions
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DARATUMUMAB (DARZALEX™) Class: Monoclonal antibody – targets CD38
Indication: Multiple myeloma who have received at least 3 prior therapies, including proteasome inhibitor and immunomodulatory agent, or who are refractory to both
Dose/Administration: 16mg/kg IV weekly, then every 2 weeks for 16 weeks, then every 4 weeks until disease progression; infusions are titrated Pre-medications: Methylprednisolone 100mg IV or equivalent, Acetaminophen 650-1000mg PO,
Diphenhydramine 25-50mg IV/PO or equivalent 1 hr prior to treatment. Corticosteroid dose may be reduced (Methylprednisolone 60mg IV) after 2nd infusion.
Post-infusion medication: Methylprednisolone 20mg PO or equivalent daily for 2 days following Daratumumab
For history of obstructive pulmonary disorder: Recommend short- and long-acting bronchodilators and inhaled corticosteroids; may be discontinued if no reactions during first 4 treatments
DARATUMUMAB (DARZALEX™) Prophylaxis for herpes zoster reactivation: Initiate within 1 week of starting Daratumumab; continue for 3 months following treatment
Special consideration: Type and cross patient for possible transfusion needs PRIOR to initiating Daratumumab; drug interferes with Indirect Antiglobulin Tests (Coombs)
Common side effects: Infusion reactions, fatigue, nausea, back pain, pyrexia, cough, upper respiratory tract infection
Monitoring: Infusion-related reactions Temperature, signs of infection
Improving adherence: Educate on importance of scheduled appointments; duration of treatment may be long due to titration and reactions – important to
start on time to allow for this Appropriate antiemetics if patient experiences nausea
Optimizing outcomes: Follow pre- and post-medication recommendations; educate patients on importance of these medications
OSIMERTINIB (TAGRISSO™)
Class: Kinase inhibitor
Indication: Metastatic EGFR T790M mutation (+) NSCLC who have progressed on or after TKI therapy; mutation must be confirmed
Dose/Administration: 80mg PO daily until disease progression or unacceptable toxicity; with or without food
Common side effects: Diarrhea, rash, dry skin, nail toxicity, eye disorders, nausea, decreased appetite, constipation
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OSIMERTINIB (TAGRISSO™)
Monitoring: QTc prolongation – ECG, electrolytes especially in patients with history or on concurrent medications
known to prolong QTc interval Baseline ECHO, then every 3 months Symptoms of interstitial lung disease (ILD), pneumonitis
Improving adherence: An oral solution can be made for those with swallowing difficulty Education on avoiding sun exposure and proper protection; addressing dermatologic toxicities Recommend taking medication with food or appropriate antiemetics if patient experiences nausea
Optimizing outcomes: Request pharmacist review for potential drug interactions
COBIMETINIB (COTELLIC™)
Class: Kinase inhibitor
Indication: Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation; in combination with Vemurafenib
Dose/Administration: 60mg PO daily on Day 1-21 of 28-day cycle until disease progression or unacceptable toxicity; with or without food
Common side effects: Diarrhea, photosensitivity reaction, nausea, pyrexia, vomiting
COBIMETINIB (COTELLIC™)
Monitoring: Dermatologic toxicities Signs, symptoms of bleeding Visual disturbances LFTs – baseline and at least monthly, CPK – baseline, then periodically ECHO – baseline, after 1st month of treatment, then every 3 months Providers – New primary malignancies (up to 6 months following last dose)
Improving adherence: Education on avoiding sun exposure and proper protection; addressing dermatologic toxicities Appropriate antiemetics if patient experiences nausea +/- vomiting
Optimizing outcomes: Request pharmacist review for potential drug interactions
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IRINOTECAN LIPOSOME (ONIVYDE™) Class: Topoisomerase inhibitor
Indication: Metastatic pancreatic adenocarcinoma with disease progression following gemcitabine-based therapy; in combination with Fluorouracil and Leucovorin
Dose/Administration: 70mg/m2 IV over 90 min every 2 weeks For patients with UGT1A1*28 allele, start at 50mg/m2 and can be increased as tolerated in
subsequent treatments Do not substitute with conventional Irinotecan
Pre-medications: Corticosteroid, antiemetic 30 min prior Do not give if ANC < 1500
IRINOTECAN LIPOSOME (ONIVYDE™) Common side effects: Diarrhea, fatigue/asthenia, vomiting, nausea, decreased appetite, stomatitis, pyrexia
Monitoring: CBC w/ differential on Days 1 and 8 of every cycle, more frequently if indicated GI symptoms Respiratory symptoms Temperature, signs of infection
Improving adherence: Atropine, Loperamide if appropriate for diarrhea Appropriate antiemetics if patient experiences nausea +/- vomiting
Optimizing outcomes: Request pharmacist review for potential drug interactions Observe ANC criteria for treatment
TRIFLURIDINE/TIPIRACIL (LONSURF®) Class: Nucleoside metabolic inhibitor/Thymidine phosphorylase inhibitor
Indication: Metastatic colorectal cancer with prior treatment with fluoropyrimidine-, oxaliplatin-, irinotecan-based chemotherapy, anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type)
Dose/Administration: 35mg/m2 PO BID on Days 1-5, Days 8-12 of each 28-day cycle until disease progression or unacceptable toxicity; take within 1 hr of morning and evening meals Dose can be titrated up to max 80mg/m2 BID
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TRIFLURIDINE/TIPIRACIL (LONSURF®) Common side effects: Anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, pyrexia
Monitoring: CBC with differential – prior to and on Day 15 of each cycle Temperature, signs of infection Signs, symptoms of bleeding GI symptoms
Improving adherence: Appropriate antiemetics if patient experiences nausea +/- vomiting
Optimizing outcomes: Education on taking medication within 1 hr of meal Education on importance of lab monitoring
TRABECTEDIN (YONDELIS®)
Class: Alkylating agent
Indication: Advanced soft tissue sarcoma (STS), liposarcoma, leiomyosarcoma subtypes who have received prior chemotherapy, including anthracycline-based regimen
Dose/Administration: 1.5mg/m2 IV over 24 hr every 3 weeks until disease progression or unacceptable toxicity Pre-medication: Dexamethasone 20mg IV or equivalent 30 min prior to Trabectedin Administration via central line recommended
TRABECTEDIN (YONDELIS®) Common side effects: Nausea, fatigue, vomiting, diarrhea, constipation, decreased appetite, dyspnea, headache, fever, cough, neutropenia, anemia
Monitoring: CBC with differential LFTs Cardiac function evaluation – baseline and every 2-3 months until discontinuation GI symptoms Respiratory symptoms Temperature, signs of infection
Improving adherence: Appropriate antiemetics if patient experiences nausea +/- vomiting
Optimizing outcomes: Follow pre-medication recommendation Request pharmacist review for potential drug interactions
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SONIDEGIB (ODOMZO®)
Class: Hedgehog pathway inhibitor
Indication: Locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation, or those who are not candidates for surgery or radiation
Dose/Administration: 200mg PO daily on an empty stomach until disease progression or unacceptable toxicity
Boxed warning: Embryo-fetal toxicity
SONIDEGIB (ODOMZO®) Common side effects: Muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, headache, myalgia, abdominal pain, pain, vomiting, pruritis
Monitoring: Baseline CK, SCr then periodically; musculoskeletal symptoms GI symptoms
Improving adherence: Appropriate antiemetics if patient experiences nausea +/- vomiting
Optimizing outcomes: Education on taking medication on empty stomach Request pharmacist review for potential drug interactions Education on importance of recommended lab monitoring
PANOBINOSTAT (FARYDAK®)
Class: Histone deacetylase inhibitor
Indication: Multiple myeloma who have received at least 2 prior regimens, including Bortezomib and an immunomodulatory agent; in combination with Bortezomib and Dexamethasone
Dose/Administration: 20mg PO once daily 3 times per week for 2 weeks per 3-week cycle; with or without food Additional 8 cycles for patients with clinical benefit, unless unresolved or significant toxicities
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PANOBINOSTAT (FARYDAK®)
Cycles 1-8
Cycles 9-16 Panobinostat – same days Bortezomib – Days 1, 8 Dexamethasone – Days 1, 2, 8, 9
Days 1-7 Days 8-14 Days 15-21
Panobinostat 1 3 5 8 10
12
Rest period
Bortezomib 1 4 8 11
Rest period
Dexamethasone 1 2 4 5 8 9 11
12
Rest period
PANOBINOSTAT (FARYDAK®) Common side effects: Diarrhea, fatigue, nausea, peripheral edema, decreased appetite, pyrexia, vomiting
Monitoring: GI symptoms Temperature, signs of infection Cardiac changes, ECG and electrolytes – baseline and periodically CBC with differential, signs of bleeding LFTs
Improving adherence: Barriers – complicated regimen Reinforce and provide tools to keep track of treatment schedule – detailed calendar Antidiarrheal agents and antiemetics as appropriate
Optimizing outcomes: Educate on importance of electrolyte monitoring and replacement Request pharmacist review for potential drug interactions
EXPANDED INDICATIONS
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NIVOLUMAB (OPDIVO®) Indication Dosing/Administration Common Side Effects Other
Unresectable or metastatic melanoma
Monotherapy: 3mg/kg IV over 60 min every 2 weeks
Monotherapy: Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea
Potential for increased side effects/toxicities in combination with Ipilimumab
With Ipilimumab: 1mg/kg IV over 60 min weekly for 4 weeks, the 3mg/kg every 2 weeks
With Ipilimumab: Fatigue, rash, diarrhea, nausea, vomiting, pyrexia, dyspnea
Metastatic non-small cell lung cancer (NSCLC)- progression on platinum-based therapy
3mg/kg IV over 60 min every 2 weeks
Fatigue, musculoskeletal pain, decreased appetite, cough, constipation
If EGFR or ALK , must have had prior treatment
Advanced renal cell carcinoma who received prior anti-angiogenic agents
3mg/kg/IV over 60 min every 2 weeks
Asthenic conditions, cough, nausea, rash, dyspnea, constipation, diarrhea, decreased appetite, back pain, arthralgia
NIVOLUMAB (OPDIVO®)
Monitoring: Infusion-related reactions Potential side effects – there are many which can be serious
Optimizing outcomes: Closely monitor for side effects. It may be helpful to develop a standard list of questions to ask your patients – Lung symptoms, GI symptoms – indicating colitis or liver problems, gland problems, kidney symptoms,
skin symptoms, symptoms of brain inflammation Can specific complex assessment be incorporated into your system for patients on Nivolumab?
PEMBROLIZUMAB (KEYTRUDA®) Indication Dose/Administration Common Side Effects Other
Unresectable or metastatic melanoma
2mg/kg IV over 30 min every 3 weeks
Fatigue, rash, pruritis, diarrhea, nausea, constipation, decreased appetite
Metastatic NSCLC – progression on platinum-based therapy
2mg/kg IV over 30 min every 3 weeks
Fatigue, decreased appetite, dyspnea, cough
If EGFR or ALK , must have had prior treatment
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PEMBROLIZUMAB (KEYTRUDA®) Monitoring: Infusion-related reactions Multiple potential side effects/toxicities
Optimizing outcomes: Closely monitor for side effects. It may be helpful to develop a standard list of questions to ask your patients – Lung symptoms, GI symptoms – indicating colitis or liver problems, gland problems, kidney symptoms,
skin symptoms Can specific complex assessment be incorporated into your system for patients on Pembrolizumab? Or
PD-1 inhibitors?
QUESTIONS?
RESOURCE: DERMATOLOGIC TOXICITIES N Tang, D Ratner. Managing Cutaneous Side Effects From Targeted Molecular Inhibitors for Melanoma and Nonmelanoma Skin Cancer. Dermatol Surg. 2016 Jan;42 Suppl 1:S40-8.