Lisa M. Holle, PharmD, BCOP, FHOPA is an assistant clinical professor, University of Connecticut School of Pharmacy, Storrs, Conn.

Lisa M. Holle, PharmD, BCOP, FHOPA

The increasing number of drugs and complexity of drug therapy in the treatment and prevention of cancer requires advanced and specialized knowledge and experience. Board-certified oncology pharmacists (BCOPs) are stepping in to meet this need.

Oncology pharmacists represent a broad range of expertise and work in a variety of settings. Most commonly, they provide direct patient care using an evidence-based patient-centered medication therapy management approach. However, they may also be involved in nondirect patient care, such as practice management, investigational drugs or clinical trials, pharmaceutical industry, regulatory agencies, and health plan sponsors/pharmacy benefit managers. In many cases, an advanced level of certification can allow for a higher salary, promotions, and new practice opportunities.

Related article: Why I Became a Board-Certified Geriatric Pharmacist

Certification allows me to practice at an advanced level of pharmacy practice in a complicated disease state, and work in multiple practice settings. Currently, I work in a team-based practice alongside a medical oncologist. Together, we review patient histories and develop cancer treatment plans throughout these patients’ disease. My expertise in understanding the complex therapies is important to effectively monitor for and prevent and manage cancer- and drug-related adverse events. I’m recognized by my institution and profession as someone who is well-qualified to be a provider on the healthcare team. 

Several pathways exist to board certification. Most commonly, pharmacists complete an advanced pharmacy practice residency in oncology or participate in on the job training.

 However, the only formal method to determine if pharmacists are qualified to contribute at advanced practice levels is the Board of Pharmacy Specialties (BPS) oncology pharmacy board examination.

To take the oncology board-certification exam, pharmacists must complete a:

Postgraduate year 1 (PGY1) general residency and a PGY2 oncology residency program;

PGY1 program and two additional recent years of oncology pharmacy experience after licensure; or

Four years of recent oncology pharmacy practice experience.

Recertification must be done every seven years and can be accomplished through re-examination or completion of 100 hours of continuing education specifically designated as BCOP appropriate.

Related article: The Value of Board-Certified Psychiatric Pharmacists

Certification in oncology allows the pharmacist to demonstrate to the healthcare team, employers, and patients/caregivers that he/she is uniquely trained and educated to meet the specialized needs of oncology patients. The oncology pharmacy board exam ensures that the pharmacist has a thorough knowledge of pathophysiology and molecular biology of cancer; therapeutics, patient management and education; clinical trials and research; practice management; and public health. With this knowledge, they have the unique expertise to be able to manage cancer- and treatment-related problems that are not encountered in other disease states.  

Articles

New developments in cancer treatment require medication experts-here's how you can become that expert.

Why You Should Become Board Certified in Oncology

	The FDA approved atezolizumab (Tecentriq) to treat advanced or metastatic urothelial carcinoma on May 18, 2016, and metastatic non-small cell lung cancer (NSCLC) on October 18, 2016. Atezolizumab was approved for patients with either of these cancers who experience worsening of their disease during or after treatment with platinum-based chemotherapy. However, those with NSCLC who have epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase tumor (ALK) aberrations should first fail appropriate therapies before starting atezolizumab.

 Patients with urothelial cancer or NSCLC who have recurrence of their cancer after treatment have very poor prognosis. Both urothelial cancer and NSCLC cells express programmed death ligand 1 (PD-L1), a transmembrane protein. PD-L1 binds to programmed death 1 (PD-1) on the surface of T lymphocytes, which inhibits cytotoxic T-cell activity, T-cell proliferation, and cytokine production.

 Atezolizumab works by binding and inhibiting the action of PD-L1 which allows the immune system to help eradicate the cancer. Atezolizumab is a first-in-class medication and the only FDA-approved drug that targets PD-L1. It is also the first new drug in two decades that may be used to treat bladder cancer.

	Atezolizumab was approved for urothelial carcinoma based on the results of the IMvigor 210 study.

 IMvigor 210 was an open-label, multicenter, single-arm, phase 2 trial that enrolled 315 patients with inoperable locally advanced or metastatic urothelial carcinoma in which the cancer was progressing following platinum-based chemotherapy. Three hundred and ten patients received 1200 mg atezolizumab given IV on day 1 of a 21-day cycle. Efficacy was assessed by an independent review of a facility-assessed overall response rates (ORR) (according to Response Evaluation Criteria in Solid Tumors v1.1) and an investigator-assessed ORR dependent on immune-modified RECIST.

	The IMvigor 210 study found that 15% of patients responded to treatment with atezolizumab (95% confidence interval [CI], 11-20, p=0.0058): 5% of all patients achieved complete response (CR) and 10% achieved partial response (PR).

 The median duration of response was not determined despite a median follow-up time of 11.7 months. A subgroup analysis using modified RECIST criteria found patients who displayed ≥5% expression of PD-L1 in tumor infiltrating cells had better outcomes with atezolizumab than those with <5% PD-L1 expression. One hundred patients with ≥5% expression had an ORR of 27%, with CR 8% and PR 19% (95% CI, 19-37, p<0.0001), whereas 107 patients with ≥1% but <5% expression had an ORR of 17%, with CR 6% and PR 11%. The remaining 103 patients with <1% expression had an ORR of 13%, with CR 2% and PR 11%.

	Atezolizumab was approved to treat NSCLC based on results of both a phase 2 study (POPLAR, n=287) and a phase 3 study (OAK, n=850).

 These international, multicenter, open-label studies randomized patients with advanced or metastatic NSCLC patients who progressed after previous treatment. In a 1:1 ratio patients were assigned to receive either 1200mg IV atezolizumab or 75mg/m

In each case the infusion was given once every 3 weeks and both studies used overall survival (OS) as their primary endpoint.

	The OAK study revealed that OS was 13.8 months (range, 11.8 - 15.7) for atezolizumab compared to 9.6 months (range, 8.6 - 11.2) with docetaxel (hazard ratio, 0.74; 95% CI, 0.63–0.87; p=0.0004).

 The POPLAR study determined that the median OS for patients on atezolizumab was 12.6 months (range, 9.7, 16.0) compared to 9.7 months (range, 8.6, 12.0) with docetaxel (HR, 0.69; 95% CI, 0.52–0.92).

 The POPLAR study finds that both docetaxel and atezolizumab had an ORR of 15%. However, 1 patient treated with atezolizumab had a CR compared to none with docetaxel.

	Some of the most common side effects (≥ 20%) experienced by patients treated with atezolizumab include fatigue, decreased appetite, nausea, urinary tract infections. Common side effects unique to treating urothelial cancer include pyrexia or constipation, while some patients treated for NSCLC may experience dyspnea or cough. The most common grade 3 or 4 adverse events (≥ 2%) include urinary tract infection, or anemia. Additional serious side effects unique to treating urothelial cancer included hematuria, acute kidney injury, or venous thromboembolism as well as sepsis, musculoskeletal pain, dysphagia, or pneumonia in patients being treated for NSCLC.

	Atezolizumab has no contraindications at this time; however, immune-mediated inflammatory adverse effects (eg, pneumonitis, hepatitis, colitis, endocrinopathies, etc) can occur and may require treatment interruption or discontinuation depending on severity. For example, if aspartate transaminase (AST) or alanine transaminase (ALT) levels are 3 to 5 times greater than the upper limit of normal (ULN) or if total bilirubin is 1.5 to 3 times ULN during treatment, atezolizumab should be withheld. If AST or ALT are greater than 5 times ULN or bilirubin is greater than 3 times ULN during treatment, atezolizumab should be permanently discontinued.

 Similarly, patients with active infections or immune-modulated inflammation, such as but not limited to pneumonitis, colitis, pancreatitis, and ocular inflammation, may require treatment changes or discontinuation; guidance may be found in the full prescribing information. Patients with endocrine dysfunction, such as thyroid disorders or type 1 diabetes mellitus, should be monitored throughout treatment.

	The potential for atezolizumab to interact with any other medications is unknown at this time. Atezolizumab may cause fetal harm. However, no data exist on use in pregnant women

	Atezolizumab is supplied in single-dose vials at doses of 1200 mg/20mL (60 mg/mL). It is given in a single 1200 mg IV infusion over 60 minutes every 21 days until disease progression or until the patient experiences unacceptable toxicity. If the patient tolerates the first dose, subsequent atezolizumab infusions may be given over 30 minutes.

 No dose adjustments are necessary for hepatic or renal impairment before treatment.

	Atezolizumab should not be given as an IV push or bolus and must not be co-administered with other drugs through the same IV line. An in-line filter that is sterile, non-pyrogenic, and low protein binding with a pore size of 0.2 to 0.22 microns may be used during administration but is not necessary.

			Tecentriq [package insert]. South San Francisco, CA. Genentech, Inc; Revised 10/2016.

			Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. 

			U.S Food & Drug Administration. Atezolizumab (Tecentriq). 

http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm525780.htm

. Published 10/19/2016. Accessed November 11, 2016.

			Fehrenbacher, Louis, Spira, Alexander, Ballinger, Marcus, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet; vol 387; 1837-1846. April 30, 2016. doi 10.1016/S0140-6736(16)00587-0

			Hoffman-La Roche.  A randomized Phase 3 Study of Atezolizumab (an Engineered Anti-PDL1 Antibody) Compared to Docetaxel in Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Failed Platinum Therapy – “OAK”. https://clinicaltrials.gov/ct2/show/study/NCT02008227. ClinicalTrials.gov identifier NCT02008227. Received December 6, 2013. Updated November 1, 2016. Accessed November 11, 2016.

Here: an overview of atezolizumab, the first new drug in two decades for bladder cancer and now approved for NSCLC.

Atezolizumab for Urothelial Carcinoma and Non-Small Cell Lung Cancer

	In July, the FDA approved lixisenatide (Adlyxin; Sanofi-Aventis), for the treatment of type 2 diabetes in combination with diet and exercise. It is estimated that 29.1 million people in the U.S. have received a diagnosis of type 2 diabetes.

Lisa M. HolleVarious therapies exist to treat hyperglycemia associated with diabetes. Lixisenatide is a glucagon-like-peptide-1 receptor agonist (GLP-1 RA): these agents are associated with improved glycemic control, reduced weight, and a limited risk for hypoglycemia. However, lixisenatide significantly decreases postprandial glucose compared with other GLP-1 RAs.

	The approval of lixisenatide was based on the GetGoal clinical program, composed of 13 multinational clinical trials that evaluated lixisenatide against placebo as monotherapy and as adjunct therapy to both oral antidiabetics (OADs) and insulin. More than 5,000 adults were evaluated worldwide.

 evaluated lixisenatide in 361 and 69 patients, respectively, as monotherapy. Lixisenatide was evaluated in GetGoal-F1, GetGoal-M, GetGoal-M-Asia, GetGoal-S, and GetGoal-P for combination therapy with OADs.

 All studies evaluated patients whose diabetes was inadequately controlled on OADs. GetGoal-F1 and GetGoal-M evaluated 484 and 680 patients, respectively, who were receiving ≥1500 mg/d of metformin. GetGoal-M-Asia evaluated 391 patients receiving between 1000-1500 mg/d of metformin and/or sulfonylurea at a maximum effective dose. GetGoal-S evaluated 859 patients using sulfonylureas, and GetGoal-P evaluated 484 patients receiving pioglitazone, with or without metformin.

 evaluated patients previously on OADs who had started taking insulin glargine for 12 weeks but who still had an A1c 

 evaluated uncontrolled patients on a stable dose of basal insulin with or without metformin ≥1500 mg/d. GetGoal-L-Asia11 evaluated uncontrolledAsian patients on a stable dose of basal insulin with or without a stable dose of a sulfonylurea. GetGoal-X

 compared lixisenatide once daily to exenatide twice daily, another GLP-1 RA, in 634 patients who were previously receiving metformin ≥1500 mg/d. GetGoal-Duo 2

 compared lixisenatide to insulin glulisine, a rapid acting prandial insulin, in 894 patients receiving basal insulin with or without OADs where patients had a run-in phase resulting in the discontinuation of all oral agents other than metformin and optimization of insulin glargine.

	In GetGoal-Mono, GetGoal-Mono Japan, and GetGoal-F1, patients were randomized into four groups: lixisenatide 10 mcg daily for 1 week, then 15 mcg daily for 1 week, then 20 mcg daily thereafter (2-step); lixisenatide 10 mcg daily for 2 weeks, then 20 mcg daily thereafter (1-step); placebo (2-step); or placebo (1-step). In GetGoal M, GetGoal-M-Asia, GetGoal-S, GetGoal-P, GetGoal-Duo 1, and GetGoal-L, patients were randomized to receive either lixisenatide 20 mcg daily or placebo. GetGoal-M further stratified patients to receive lixisenatide in the morning or evening. GetGoal-L-Asia randomized patients to receive a stepwise dose increase to 20 mcg daily of lixisenatide or placebo. GetGoal-X randomized patients to lixisenatide 20 mcg daily or exenatide 10 mcg twice daily. GetGoal-Duo 2 randomized patients to either lixisenatide 20 mcg daily (after a titration of 10 mcg daily x 2 weeks) or insulin glulisine daily or three times daily.

	The primary endpoint for all studies was HbA

 reduction at 12 or 24 weeks. The GetGoal phase III clinical trial program showed that lixisenatide effectively reduced A

 (range: -0.7 to -1.0%), weight (range: -0.2 to -2.96 kg), and 2-hour postprandial glucose of the immediate meal following its administration (range: -3.1 to -7.96 mmol/L).

	Lixisenatide is generally well tolerated. The most common adverse events (>  5%of patients) reported in the studies were nausea (25%), vomiting (10%), headache (9%), diarrhea (8%), dizziness (7%), and hypoglycemia (2% as monotherapy, 3% to 47% with combination therapy; more so in combination with basal insulin than OADs). Neither a one-step versus a two-step titration or morning versus evening administration appeared to have a significant impact on the rates of adverse events.

	In GetGoal-X, patients reported fewer episodes of nausea compared to exenatide twice daily (24.5% vs. 35.1%, p<0.05) and hypoglycemia (2.5% vs. 7.9%, p<0.05). Data from the ELIX

 study demonstrated no increase incidence in pancreatitis or cancers and a neutral effect on risk of cardiovascular problems. Lixisenatide is contraindicated in patients who have a hypersensitivity to lixisenatide or any product components.

	Lixisenatide is supplied as a disposable pre-filled pen for a single dose of 10 mcg (50 mcg/mL) or 20 mcg (100 mcg/mL) for subcutaneous administration to the abdomen, thigh, or upper arm. Recommended starting dose is 10 mcg/d for 14 days. On day 15, the dosage is increased to 20 mcg/d. Use is not recommended in patients with a CrCl <15 ml/min, because the drug was not well studied in this   population.

	Advise patients to rotate injection sites with each dose, as with other injectables. Patients should administer lixisenatide within one hour before the first meal of the day, preferably the same meal each day. Advise them to protect the pens from light by keeping them in the original packaging and discarding them after 14 days after first use.

	Lixisenatide delays gastric emptying and can therefore alter the absorption of oral medications taken concurrently. Medications that depend on threshold concentrations for efficacy should be administered 1 hour before lixisenatide. The same is true when a delay in a medication’s effect is undesirable. Lixisenatide can decrease serum concentrations of progestin and estrogen contraceptives. Oral contraceptives should be taken at least 1 hour before or 11 hours after lixisenatide administration.

Vincent Do, 2017 PharmD Candidate is a 4th year pharmacy student at UConn School of Pharmacy, Storrs, Conn

Lisa M. Holle, PharmD, BCOP, FHOPA is an Associate clinical Professor at UConn School of Pharmacy, Storrs, CT.

	1. Anderson SL, Trujillo JM. Lixisenatide in type 2 diabetes: latest evidence and clinical usefulness. 

	2. Fonseca VA, Alvarado-ruiz R, Raccah D, et al. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). 

	3. Seino Y, Yabe D, Takami A, et al. Long-term safety of once-daily lixisenatide in Japanese patients with type 2 diabetes mellitus: GetGoal-Mono-Japan. 

	4. Bolli GB, Munteanu M, Dotsenko S, et al. Efficacy and safety of lixisenatide once daily vs. placebo in people with Type 2 diabetes insufficiently controlled on metformin (GetGoal-F1). 

	5. Ahrén B, Leguizamo dimas A, Miossec P, Saubadu S, Aronson R. Efficacy and safety of lixisenatide once-daily morning or evening injections in type 2 diabetes inadequately controlled on metformin (GetGoal-M). 

	6. Yu pan C, Han P, Liu X, et al. Lixisenatide treatment improves glycaemic control in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (GetGoal-M-Asia). 

	7. Rosenstock J, Hanefeld M, Shamanna P, et al. Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (GetGoal-S).

	8. Pinget M, Goldenberg R, Niemoeller E, et al. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). 

	9. Riddle MC, Forst T, Aronson R, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled with newly initiated and continuously titrated basal insulin glargine: a 24-week, randomized, placebo-controlled study (GetGoal-Duo 1). 

	10. Riddle MC, Aronson R, Home P, et al. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L). 

	11. Seino Y, Min KW, Niemoeller E, Takami A. Randomized, double-blind, placebo-controlled trial of the once-daily GLP-1 receptor agonist lixisenatide in Asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (GetGoal-L-Asia). 

	12. Rosenstock J, Raccah D, Korányi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (GetGoal-X).

	13. Rosenstock J, Guerci B, Hanefeld M, et al. Prandial options to advance basal insulin glargine therapy: testing lixisenatide plus basal insulin versus insulin glulisine either as basal-plus or basal-bolus in type 2 diabetes: the GetGoal Duo-2 Trial. 

	14. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. 

FDA approves lixisenatide for type 2 diabetes

Lisa M. HolleFDA approved ixazomib (Ninlaro, Takeda) in combination with lenalidomide and dexamethasone in November 2015 to treat patients with multiple myeloma who have received at least one prior therapy. Ixazomib was granted priority review and orphan drug designations by FDA.

	When treating patients with relapsed multiple myeloma, 3-drug regimens have been shown to be superior to 2-drug regimens. Yet current treatment options often have many bothersome and dose-limiting side effects. Ixazomib is the first FDA-approved oral proteasome inhibitor. Ixazomib inhibits proteasomes that affect multiple myeloma cell growth and survival. Combined with lenalidomide and dexamethasone, this approval provides an all oral-drug regimen for patients with refractory or relapsed multiple myeloma.

	Ixazomib approval was based on a double blind, placebo-controlled, phase 3 trial that enrolled 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma.

 Of note, patients who had refractory disease to lenalidomide or proteasome inhibitor-based therapy were not eligible. Patients received either oral ixazomib 4 mg or placebo on days 1, 8, and 15 of a 28-day cycle: both groups also received 25 mg of oral lenalidomide on days 1 through 21 and 40 mg of oral dexamethasone on days 1, 8, 15, and 22.

	The primary endpoint-median progression-free survival-was measured at 20.6 months in the ixazomib group and 14.7 months in the placebo group. The hazard ratio for disease progression or death was 0.74 (95% confidence interval, 0.59 to 0.94; P=0.01). 129 events of disease progression or death occurred in the ixazomib group vs 157 in the placebo group. Subgroup analyses showed similar progression-free survival times in patients with a poor prognosis, high-risk cytogenetic abnormalities, and other high risk features.

	Ixazomib should not to be taken with strong CYP3A4-inducing drugs as it is a substrate of CYP3A4. The most common adverse events (≥20%) include diarrhea, constipation, thrombocytopenia, neutropenia, peripheral neuropathy, nausea, vomiting, peripheral edema, and back pain. Ixazomib should not be used during pregnancy or in women who are breast feeding. Effective birth control should be used by females and males with a female partner who is able to become pregnant during treatment and for 90 days after the last dose of ixazomib. Ixazomib is classified as a low emetogenic-potential drug, requiring only as-needed antiemetics. Ixazomib is cytotoxic; capsules should not be opened or crushed and direct contact with the capsule contents should be avoided. Capsules should be stored in the original packaging and removed just before dosing.

	Ixazomib is approved as a 4-mg dose to be taken by mouth on days 1, 8, and 15 of a 28-day cycle. Absorption is decreased with food; therefore, ixazomib should be taken at least one hour before or two hours after food. When taking the approved regimen, the patient take the dexamethasone and lenalidomide doses with food and the ixazomib dose on an empty stomach (at least 2 hours after food and 1 hour before food) with water. If a patient misses a dose, he or she should be instructed to take the missed dose as long as the next scheduled dose is ≥72 hours away. Ixazomib is currently available as a 4-mg, 3-mg, and 2.3-mg capsule. In patients with moderate to severe hepatic impairment, ixazomib should be decreased to a starting dose of 3 mg. Patients with severe renal impairment or end-stage renal disease who require dialysis should also begin with a starting dose of 3 mg.

Hannah Buckler, a 2017 PharmD Candidate, is a 4th year pharmacy student at UConn School of Pharmacy in Storrs, Conn. Lisa M. Holle, PharmD, BCOP, FHOPA is Associate Clinical Professor at UConn School of Pharmacy.

			Moreau P, Masszi T, Grzasko N, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621-1634

FDA approved ixazomib (Ninlaro, Takeda) in combination with lenalidomide and dexamethasone