In the United States, ovarian cancer is the fifth-leading cause of cancer deaths among women and the leading cause of gynecological cancer deaths.

 Additionally, 10% to 15% of ovarian cancer cases nationwide are a result of germline or somatic BRCA mutations.

 With cognizance of tumor genetics, practice has shifted to include targeted agents in ovarian cancer treatment.

PARP enzymes are responsible for detecting and repairing single-stranded and double-stranded DNA breaks during cell replication. BRCA1/2 mutations hinder the homologous recombination repair pathway, and tumor cells utilize PARP enzymes to repair DNA.

 For this reason, these tumors are particularly sensitive to the mechanism of PARP inhibitors.

There are 3 PARP inhibitors that are FDA approved in multiple settings of ovarian cancer: olaparib (Lynparza; AstraZeneca), rucaparib (Rubraca; Clovis Oncology), and niraparib (Zejula; GlaxoSmithKline).

 However, there are points of note for each regarding pivotal trial results, safety profiles, and significant differences (

Olaparib was the first PARP inhibitor approved in 2014 for patients with ovarian cancer with a germline BRCA mutation.

 Based on results of the phase 3 SOLO-2 trial (NCT01874353), it received approval in the maintenance setting following platinum-based therapy in recurrent ovarian cancer with an underlying BRCA mutation.

In the SOLO-2 trial, the median progression-free survival (PFS) in the olaparib arm was significantly longer than placebo at 19.1 vs 5.5 months (HR, 0.3; 95% CI, 0.22-0.41; P < .0001). Additionally, during a different phase 2 trial (NCT04858334), investigators evaluated olaparib regardless of BRCA mutation as a maintenance therapy in patients with partial response

or complete response following platinum therapy, with the results showing that PFS remained longer in the olaparib arm (8.4 vs 4.8 months) vs the placebo arm (HR, 0.35; 95% CI, 0.25-0.49; P < .0001).

 Long-term follow-up also demonstrated an overall survival benefit regardless of BRCA mutation; FDA approval for this indication followed in 2019.

In the PAOLA-1 trial (NCT02477644), investigators combined olaparib and bevacizumab, a vascular endothelial growth factor receptor inhibitor also utilized in maintenance therapy. Patients received bevacizumab up front with platinum-based therapy and were randomized to bevacizumab with either olaparib or placebo.

During the PAOLA-1 trial, the greatest benefit was seen in patients with homologous recombination deficiency (HRD) including BRCA mutations, with a median PFS of 37.2 vs 17.7 months with placebo (HR, 0.43; 95% CI, 0.28-0.66). Subsequently, the combination obtained FDA approval as up-front maintenance in this corresponding setting.

The safety profile of olaparib is consistent across all trials.

 Among the common toxicities is myelosuppression, especially anemia, which occurs in 23% to 44% of patients. Fatigue develops in approximately 67% of patients; gastrointestinal toxicities, particularly nausea, are experienced in 45% to 77% of patients. One unique concern is pneumonitis, with an incidence in less than 1% of patients during trials.

A second PARP inhibitor, rucaparib, was approved in 2016 with similar indications in ovarian cancer to olaparib.

 The ARIEL2 trial (NCT01891344) found a significant PFS benefit in patients with either a BRCA mutation or high loss of heterozygosity at a median PFS of 12.8 months vs 5.7 months, respectively, compared with 5.2 months in patients with low loss of heterozygosity (HR, 0.27; 95% CI 9.0-14.7; P < .0001).

After the submission of further positive results from the ARIEL3 trial (NCT01968213), rucaparib was approved for maintenance therapy following response to platinum-based therapy, with median PFS doubled compared with placebo at 10.8 months vs 5.4 months (HR, 0.36; 95% CI, 0.3-0.45; P < .0001).

During clinical trials, rucaparib was found to have a similar adverse effect (AE) profile to olaparib.

Anemia, fatigue, and nausea occurred at rates of 39%, 73%, and 76%, respectively. Additionally, dyspepsia and dysgeusia were more common with rucaparib than with olaparib.

 Drug-specific concerns for rucaparib included elevated liver enzymes (60%-70%) and increased cholesterol (40%-84%).

In 2017, the FDA approved niraparib for maintenance treatment of patients with recurrent epithelial ovarian cancer based on the results of the NOVA trial (NCT01847274).

 The study included patients with platinum-sensitive recurrent ovarian cancer with and without BRCA mutations, and niraparib was given to patients after their penultimate platinum regimen.

During the NOVA trial, all cohorts benefited from niraparib therapy, with a PFS of 21 months in the BRCA-mutated group in contrast with 5.5 months with placebo (HR, 0.26; 95% CI, 0.17-0.41; P < .0001).

 Both patients with HRD and non–BRCA-carrying patients also benefited from maintenance niraparib.

In the PRIMA trial (NCT02655016), investigators assessed niraparib in the first-line maintenance setting for patients responding to platinum-based therapy regardless of biomarker status.17 PFS in the HRD population was 21.9 vs 10.4 months (HR, 0.43; 95% CI, 0.31-0.59, P < .0001) and 13.8 vs 8.2 months in the overall population (HR, 0.62; 95% CI, 0.50-0.76; P < .0001).

To evaluate efficacy following relapse, investigators conducted a single-arm QUADRA trial (NCT02354586), which included heavily pretreated patients. The reported overall response rate was 28% in patients with HRD disease or a BRCA mutation (95% CI, 15.6-42.6; P = .00053).

Niraparib has a similar toxicity profile to other PARP inhibitors

; however, it is associated with the highest rates of anemia (50%-64%), neutropenia (30%-42%), and thrombocytopenia (61%-66%).

 Additionally, body weight and baseline platelet count predict increased risk of thrombocytopenia in the first month of treatment.7 Nausea occurs in 57% to 74% of patients; fatigue is seen in 57% of patients. Drug-specific concerns include hypertension (20%) and palpitations (10%).

PARP inhibitors have expanded treatment options in ovarian cancer. Drugs in this class are well tolerated, and discontinuations due to AEs are rare. All PARP inhibitors may rarely cause secondary hematologic malignancies, with incidence varying between trial and agent.

 Activity against BRCA mutations make this class valuable against breast cancer tumors harboring similar mutations.

Interest in olaparib and rucaparib in prostate and pancreatic cancer has increased due to the sensitivity of HRD pathways against proposed mechanisms in these cancers.

 There is another PARP inhibitor, veliparib, under investigation in ovarian cancer.

is a PGY-2 oncology pharmacy resident at Lifespan who obtained her PharmD from St. John’s University in New York.

is a clinical pharmacist specialist in oncology at Women & Infants Hospital in Rhode Island and a clinical assistant professor at the University of Rhode Island.

is a clinical pharmacist specialist in hematology/ oncology at Lifespan who obtained his PharmD from the University of Rhode Island.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. 

. 2018;68(1):7-30. doi:10.3322/caac.21442

Ovarian Cancer Statistics. CDC. Updated June 8, 2021. Accessed June 10, 2021. 

www.cdc.gov/cancer/ovarian/statistics/index.htm

Blackwood MA, Weber BL. BRCA1 and BRCA2: from molecular genetics to clinical medicine

 1998;16(5):1969-1977. doi:10.1200/JCO.1998.16.5.1969

Rose M, Burgess JT, O’Byrne K, Richard DJ, Bolderson E. PARP inhibitors: clinical relevance, mechanisms of action and tumor resistance. 

. 2020;8:564601. doi:10.3389/fcell.2020.564601

Lynparza. Prescribing information. AstraZeneca Pharmaceuticals; 2021. Accessed June 2, 2021. 

https://www.lynparzahcp.com/home.html/?source=lyn_d_h_15&umedium=cpc&uadpub=google&ucampaign=lynparzahcpovarian_branded_alone_2020_hcp&ucreative=branded_alone_agnostic_ph&uplace=lynparzaastrazeneca&outcome=hcp&cmpid=1&gclid=Cj0KCQjwm9yJBhDTARIsABKIcGaiqCG40AGY61khiL2_GjdUMF0KxB7d_0-0Bjjx_v-ckFV7TQA6gMYaAh7wEALw_wcB&gclsrc=aw.ds

Rubraca. Package insert. Clovis Oncology, Inc; 2020. Accessed June 2, 2021. 

https://clovisoncology.com/pdfs/RubracaUSPI.pdf

Zejula. Prescribing information. GlaxoSmithKline; 2021. Accessed June 2, 2021. 

https://zejula.com/about/why-zejula/?cc=ps_NCPHFWC40C1083019&mcm=220014&gclid=Cj0KCQjwm9yJBhDTARIsABKIcGZG-6B1dJvUpcsKuCekppvO7UEwwSVEAn1E2gw-D8qFOp_iKwebWGUaAiHdEALw_wcB&gclsrc=aw.ds

Domchek SM, Aghajanian C, Shapira-Frommer R, et al. Efficacy and safety of olaparib monotherapy in germline BRCA1/2 mutation carriers with advanced ovarian cancer and three or more lines of prior therapy

. 2016;140(2):199-203. doi:10.1016/j.ygyno.2015.12.020

Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. 

. 2017;18(9):1274-1284. doi:10.1016/S1470-2045(17)30469-2

Ledermann JA, Harter P, Gourley C, et al. Overall survival in patients with platinum-sensitive recurrent serous ovarian cancer receiving olaparib maintenance monotherapy: an updated analysis from a randomised, placebo-controlled, double-blind, phase 2 trial. 

 2016;17(11):1579-1589. doi:10.1016/S1470-2045(16)30376-X

Ray-Coquard I, Pautier P, Pignata S, et al. Phase III PAOLA-1/ENGOT-ov25: maintenance olaparib with bevacizumab in patients with newly diagnosed, advanced ovarian cancer treated with platinum-based chemotherapy and bevacizumab as standard of care. 

 2019;381:2416-2428. doi:10.1136/esmoopen-2020-001110

Swisher EM, Lin KK, Oza AM, et al. Rucaparib in relapsed, platinum-sensitive high-grade ovarian carcinoma (ARIEL2 Part 1): an international, multicentre, open-label, phase 2 trial. 

. 2017;18(1):75-87. doi:10.1016/S1470-2045(16)30559-9

Coleman RL, Oza AM, Lorusso D, et al; ARIEL3 investigators. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial. 

. 2017;390(10106):1949-1961. doi:10.1016/S0140-6736(17)32440-6

Lord R, Mirza MR, Woelber L, et al. Safety and dose modification for patients with low body weight receiving niraparib in the ENGOT-OV16/NOVA phase III trial. 

. 2018;149(suppl 1):11. doi:10.1016/j.ygyno.2018.04.031

Moore KN, Secord AA, Geller MA, et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. 

. 2019;20(5):636-648. doi:10.1016/S1470-2045(19)30029-4

LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. 

. 2019;20(1):e15-e28.
doi:10.1016/S1470-2045(18)30786-1

González-Martín A, Pothuri B, Vergote I, et al; PRIMA/ENGOT-OV26/GOG-3012 Investigators. Niraparib in patients with newly diagnosed advanced ovarian cancer. 

. 2019;381(25):2391-2402. doi:10.1056/NEJMoa1910962

Coleman RL, Fleming GF, Brady MF, et al. Veliparib with first-line chemotherapy and as maintenance therapy in ovarian cancer. 

 2019;381(25):2403-2415. doi:10.1056/NEJMoa1909707

There are 3 PARP inhibitors that are FDA approved in multiple settings of ovarian cancer.

Overview of PARP Inhibitors in the Treatment of Ovarian Cancer

Britny Rogala, PharmD, BCOP

Despite psoriasis being the most frequently experienced immune-mediated inflammatory skin disease, there is no known cure for it. Instead, current treatments are aimed at reducing the symptoms of psoriasis, which include dry, scaly, and itchy raised skin patches known as plaques. Plaque psoriasis, the most common form of psoriasis, occurs in more than 80% of all patients with psoriasis.

The complex pathophysiology is not clearly elucidated, but it is thought to consist of a feed-forward inflammatory mechanism involved in the pathway of T-helper cell type 17 (T

The amount, color, and severity of plaques vary among individuals and over time. Plaques are typically symmetrical and occur primarily on the elbows, knees, lower back, and scalp, where they often originate. In addition, the patches may present as different colors based on disease progression and skin color, with hyperpigmentation occurring during healing, particularly in darker-skinned individuals.

Flare-ups occur in a cyclic manner for a few weeks or months at a time.

Although the major cause of plaque psoriasis is polygenetic, resulting from the presence of multiple alleles and loci associated with psoriasis, environmental and behavioral factors may exacerbate the severity of symptoms in genetically predisposed individuals.

These factors include some infections (eg, streptococcal infection), certain medications (eg, β-blockers and nonsteroidal anti-inflammatory drugs), smoking tobacco, and stress. Trauma to the skin, which may include scratching or pressure from animal bites, sunburn, or skin lesions, can also create new or more severe plaques in a reaction known as the Koebner phenomenon.

Plaque psoriasis poses a significant burden to individuals. Moderate to severe psoriasis is associated with a 70% higher risk of developing comorbid conditions, including cardiometabolic diseases such as dyslipidemia, hypertension, vascular inflammation, and coronary atherosclerotic plaques, as well as obesity, diabetes mellitus, and anxiety and depression.

Approximately one-third of those with psoriasis develop psoriatic arthritis.

There is also a substantial economic burden imposed by plaque psoriasis due to the frequency of inpatient and outpatient visits. Treatment is the highest contributor to costs, accounting for 37.5% of total disease-related spending for those with the disease.

Different therapeutic options may be available to patients based on the degree of illness: mild plaque psoriasis is classified by localized rash covering less than 3% to 5% of the skin, while moderate to severe plaque psoriasis involves more extensive skin surface lesions.

 The Physician’s Global Assessment (PGA) serves to quantify symptom severity on a scale from 0 to 4, with higher scores indicating more severe psoriasis.

Topical therapies are typically the first course of action in treating mild psoriasis, and include topical corticosteroids, vitamin D analogs, calcineurin inhibitors, and keratolytics. Targeted phototherapy, which uses ultraviolet (UV) radiation to treat a small patch of affected skin, may also be used.

For moderate or severe psoriasis, phototherapy using UV-B or psoralen-UVA radiation suppresses DNA synthesis and expression involved in the pathology of the disease. Biological agents have been indicated for use in more serious disease states, and act as tumor necrosis factor-alpha (TNF-α) inhibitors, interleukin-12/23 (IL-12/23) inhibitors, interleukin-17 (IL-17) inhibitors, and interleukin-23 (IL-23) inhibitors.

There are also oral systemic agents, but these are typically prescribed only when patients have limited access to biologics or wish to avoid injectables, as they generally have lower efficacy than biological counterparts. Topical medications are often used in conjunction with other therapies in patients with moderate to severe plaque psoriasis.

Tapinarof (Vtama) is a novel drug approved by the FDA in May 2022 and indicated for use in adults with any level of severity of plaque psoriasis.

 The first-in-class, steroid-free topical medication is an aryl hydrocarbon receptor antagonist whose mechanisms of action have not yet been made clear, but it is thought to bind the aryl hydrocarbon receptor, a ligand-dependent transcription factor that modulates T

17 cell expression, skin barrier protein expression of filaggrin and loricrin keratinocytes, and antioxidant enzyme gene expression.

 Tapinarof cream 1% is indicated for topical use only and it is recommended to apply a thin layer to affected areas once daily.

Tapinarof was approved following a phase 2b clinical trial that determined adequate dosage and efficacy, followed by PSOARING 1 (n = 510) and PSOARING 2: 2 identical, phase 3, multicenter, randomized, double-blind, vehicle-controlled trials. Participants aged 18-75 years (median age, 51) with moderate to severe plaque psoriasis, defined by baseline PGA scores of 2 (mild) to 4 (severe) on a scale of 0-4 and affected body surface area of 3%-20% were included in the study, with at least 80% of participants belonging to the “moderate” classification. Participants were randomly assigned in a 2:1 ratio to use tapinarof 1% or vehicle cream once daily for 12 weeks.

Improvement in plaque psoriasis, defined as a PGA score of 0 (clear) or 1 (almost clear) and a decrease by at least 2 points at week 12, was achieved by 35.4% and 40.2% of participants in the tapinarof groups and 6.0% and 6.3% of participants in the vehicle-controlled groups in PSOARING 1 and PSOARING 2, respectively. Adverse effects (AEs) experienced in both trials by the tapinarof group included headache, upper respiratory tract infection, and local events, such as folliculitis, nasopharyngitis, contact dermatitis, and pruritus.

Those who completed 1 of the 2 studies were invited to participate in PSOARING 3, a long-term efficacy study. A total of 763 participants chose to continue in the study, which analyzed tolerability and duration of tapinarof 1%.

After 40 weeks of open-label treatment with tapinarof 1%, it was found that 40.9% of patients experienced complete disease clearance (PGA = 0), with the mean duration following cessation of treatment of 130.1 days or 52 weeks with intermittent use. No tachyphylaxis was observed, and AEs were consistent with previous studies.

Tapinarof, demonstrated to have lasting effects for a range of disease severities and with no significant AEs, can be used for adults with psoriasis either on its own or in combination with other therapies. Due to the unique mechanism of action of tapinarof compared with existing therapies, it may be effective in targeting the pathophysiology of psoriasis rather than symptoms alone.

Pharmacists treating patients with psoriasis should be aware of this novel class of medication and be prepared to address questions regarding its use. They should also continue to monitor for any local AEs and advise patients on appropriate application methods to maximize the effectiveness of this treatment. The efficacy of tapinarof in both short- and long-term studies on patients with varying baseline symptom severity shows that it is an option to take into consideration.

National Psoriasis Foundation. Plaque psoriasis. Accessed July 8, 2022. 

Armstrong AW, Read C. Pathophysiology, clinical presentation, and treatment of psoriasis: a review. 

. 2020;323(19):1945-1960. doi:10.1001/jama.2020.4006FDA.

Kim GK, Del Rosso JQ. Drug-provoked psoriasis: is it drug induced or drug aggravated? understanding pathophysiology and clinical relevance. 

Lee S, Xie L, Wang Y, Vaidya N, Baser O. Comorbidity and economic burden among moderate-to-severe psoriasis and/or psoriatic arthritis patients in the US Department of Defense population. 

. 2018;21(6):564-570. doi:10.1080/13696998.2018.1431921

Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 trials of tapinarof cream for plaque psoriasis. 

. 2021;385(24):2219-2229. doi:10.1056/NEJMoa2103629

Vtama. Prescribing information. Dermavant Sciences, Inc; 2022. Accessed June 17, 2022. www.vtama.com/docs/DMVT_VTAMA_PI.pdf

Strober B, Gold LS, Bissonnette R, et al. Tapinarof cream 1% once daily for plaque psoriasis: long-term extension trial of a novel therapeutic aryl hydrocarbon receptor modulating agent. 

. 2022;6(2):s5. Poster. Accessed July 15, 2022. https://jofskin.org/index.php/skin/article/view/1521/pdf

Tapinarof is a first-in-class topical steroid-free aryl hydrocarbon receptor antagonist intended to mitigate the symptoms of plaque psoriasis. 

Approval of Tapinarof Introduces New Class of Topical Treatments for Management of Plaque Psoriasis

Elise Palatine

of many pharmacists, the FDA’s Current Good Manufacturing Practices (CGMP) have unduly raised the bar of compliance under the authority and jurisdiction of state boards of pharmacies (SBOP).

But compared with the potential financial- and safety-related consequences of noncompliance, CGMPs should not be seen as a regulatory burden but as a reliable safeguard against disastrous outcomes, a point made clear in 2012 when improper compounding at the New England Compounding Pharmacy sparked an outbreak of fungal meningitis. The outbreak resulted in 64 deaths and 751 injuries.

 As of November 2017, no studies had been published that provided financial data on the impact of CGMPs on drug-compounding pharmacies’ compliance or the significance to protecting the health of the public. But the FDA’s SBOP data provide compelling evidence that, for the most part, compounding pharmacies do not realize the importance that CGMPs have on sustaining compounded medicines as a viable resource to patients.

Although much work still needs to be done to eliminate the risk of exposing the public to poorly compounded drugs, education is the best mechanism for changing risky behavior by compounding pharmacists. With the right knowledge about what the FDA and the public require from quality compounded drug products, the FDA’s mission can be realized in a way that works to everyone’s benefit. Compounding pharmacists should consider these questions to understand the risks of failing to adopt CGMPs throughout their organizations: How do CGMPs apply to compounding? How does a compounding pharmacy comply with CGMPs? How does the FDA assess the state of CGMP compliance once implemented? Rather than contending that regulators are misapplying the rules and that the FDA, in the words of Congress, is “overstepping” its regulatory authority, educating and implementing appropriate strategies that enhance patient safety while making economic sense will best serve compounding pharmacies in the long run.

A debate has been brewing between compounding pharmacists and the FDA. Following the New England Compounding Center tragedy in 2012, Congress acted quickly to promulgate new rules codified in the Drug Quality  and Security Act (DQSA) that gave the FDA regulatory oversight of drug compounding activity in the United States and its territories.

Since then, some statutory practices that had evolved over the past 25 years are being questioned when applied to drug compounding. These concerns have been further accelerated by an FDA now more proactive in its initiative to bring its operations into the 21st century. CGMPs are the cornerstone of the Food, Drug and Cosmetic (FD&C) Act. CGMPs provide a mechanism for drug manufacturers to produce effective, pure, and safe drug products and for the FDA to inspect and issue observations, warnings, injunctions, and consent decrees to drug manufacturers that fail to comply with the CGMP rules.

Since the DQSA was passed in 2013, the FD&C Act has been extended to additional drugs for humans and for veterinary compounding.

The FDA’s list of inspections, recalls, and other enforcement actions shows that regulators not only intend to make good on this initiative but are actively doing so. With many pharmacies not registered as outsourcing facilities, it is certain that the FDA will continue to leverage its enforcement of CGMPs on compounding pharmacies to protect the public from poorly compounded drugs.

is president of GER Compliance in Fenton, Missouri.

Outterson K. Regulating compounding pharmacies after NECC. 

2012;367(21):1969-1972. doi:10.1056/NEJMp1212667

Drug compounding. US Government Accountability Office. November 2016. Accessed December 23, 2021. https://www.gao.gov/assets/gao-17-64.pdf

Properly implemented CGMP should not be seen as a regulatory burden but a remedy to poorly compounded drugs.

Current Good Manufacturing Practices Are Reliable Safeguard

Gary E. Ritchie

With the cost of prescription medications rising each year, one of the most harmful results is cost-related nonadherence (CRN). Many socioeconomic factors contribute to CRN, including high out-of-pocket costs for medications, lack of health insurance, low income, and minority status.

 To understand how these factors play a role in CRN, it is critical to first understand the impact each has on patient access to needed treatment. By understanding these factors, pharmacy technicians can play a crucial role in removing some of these barriers for patients initiating treatment with high-cost prescription medications.

A cancer diagnosis, for instance, can represent an incredibly difficult time in an individual’s life. The overall treatment plan, as well as adverse effects and cost, is among many considerations a patient and family members may have to work through.

In 2020, an estimated 1.8 million new cases of cancer were diagnosed in the United States, with that number expected to rise in 2021.

 In 2020, the national costs for cancer care were estimated at $208.9 billion, which includes costs for medical services and oral prescription drugs.

 Some of the most expensive prescription costs by cancer type were breast cancer at $3.5 million, leukemia at $3.2 million, lung cancer at $1.8 million, prostate cancer at $1.7 million, and renal cancer at $1.3 million.

 The national costs are projected to increase to $246 billion by 2030, based on population growth.

 These high out-of-pocket costs are unattainable for most patients, even for families with 2 incomes. Whether the cause is related to inadequate or no insurance coverage or insufficient funding, these barriers often make it difficult for patients to begin treatment.

In addition to cost, ethnic and racial disparities play a role in CRN. The results of a National Health Interview Survey from 2006 to 2012 showed that among 10,998 cancer survivors, 1397 reported CRN. Among those older survivors, Black individuals were 2.64 times more likely and Hispanic individuals 2.07 times more likely than White individuals to report CRN. Younger, Hispanic survivors of cancer were 1.61 times more likely than White survivors of cancer to report CRN. Based on continual increases in the cost of prescription drugs, these findings support the importance of closely monitoring CRN in high-risk subgroups and offering them support services to promote medication adherence.

Most drugs, as indicated by the third-party payer (TPP) in the specialty tier of a prescription benefit plan, may require prior approval—commonly referred to as prior authorization (PA)—that may be a drug access barrier for patients. PA is a therapy utilization management process employed by TPPs, aimed at controlling costs and managing drug safety.

 Select oral oncology medications may be alternatively billed through a patient’s Medicare Part B plan. There are 2 types of services covered under Part B: medically necessary and preventive services.

 In consideration of these factors, technicians often play a crucial role in obtaining PAs and securing other forms of financial assistance available to patients.

Technicians can submit PAs effectively and efficiently by providing clinical documentation—such as evidence-based literature and genetic testing, laboratory, and pathology results—to the TPPs to facilitate a successful, timely outcome. It is also important that technicians be trained to determine when parts of the submission process are not within their scope of practice and to seek further guidance from a practitioner. Additionally, there may be instances when a PA is denied and a technician trained in PAs can seek an appeal via the standard process outlined by TPPs, which may include an option for a peer-to-peer encounter between the health plan medical director and the prescribing physician.

In addition to assisting with the insurance portion of a patient’s treatment, technicians can help with removing the financial burden brought on by many prescribed treatment plans. There are many resources available to assist with these financial concerns, including commercial copay cards, foundation grants, free trials, manufacturer free drug programs, and voucher programs.

Co-pay assistance cards can only be used with patients who have commercial insurance. The cards do not have income requirements and typically cover most of or all the co-pay. However, there may be annual benefit limits. Trial cards or voucher programs are limited to 1 use per lifetime and do not have restrictions on whether a patient is insured or uninsured. They also have no income requirements and provide the patient with free medication to begin treatment immediately.

Technicians may also tap various foundations to assist on a patient’s behalf and obtain grants specific to a disease state. A patient’s eligibility largely depends on disease diagnosis and financial need, which typically is measured by national poverty levels. In addition, some foundations or grants may be closed for enrollment because of insufficient funding. Finally, when all options are exhausted, technicians may attempt to assist patients by obtaining free medications from the manufacturer. This scenario typically happens when available funds obtained are insufficient to cover the coinsurance or co-pay; no grants are available; the patient does not qualify for foundation or grant assistance; the patient does not have prescription drug coverage; the PA is denied; or it is required for compassionate, off-label use for a disease state.

Not all patients are approved for free medication through a manufacturer’s patient assistance program, because of eligibility being largely based on income. This should not deter technicians from pursuing assistance. They can further advocate for patients who have been denied an appeal by submitting a letter of financial hardship; providing financial documents including expenses, medical bills, and receipts; and including a letter of medical necessity from the provider.

Financial burdens and insurance barriers can be managed by skilled pharmacy patient advocates, often technicians, who work closely with insurance companies and understand the criteria required to obtain approvals. They can use resources available to them, such as co-pay cards, foundations, or grants, as well as free trial cards or medication from the manufacturer.

, CPhT, is a pharmacy technician at Banner Health.

Zhang JX, Meltzer DO. Risk factors for cost-related medication non-adherence among older patients with cancer. Integr Cancer Sci Ther. 2015;2(6):300-304.

Cancer statistics. National Cancer Institute. Updated September 25, 2020. Accessed October 15, 2021. https://www.cancer.gov/about-cancer/understanding/statistics

Financial burden of cancer care. National Cancer Institute. Updated July 2021. Accessed October 15, 2021. https://progressreport.cancer.gov/after/economic_burden

Mariotto AB, Enewold L, Zhao J, Zeruto CA, Yabroff KR. Medical care costs associated with cancer survivorship in the United States. Cancer Epidemiol Biomarkers Prev. 2020;29(7):1304-1312. doi:10.1158/1055-9965.EPI-19-1534

Lee M, Salloum RG. Racial and ethnic disparities in cost-related medication non-adherence among cancer survivors. J Cancer Surviv. 2016;10(3):534-544. doi:10.1007/s11764-015-0499-y

Behrendsen J. A brief history of how we got to electronic prior authorization. CoverMyMeds.com. December 1, 2017. Accessed October 15, 2021. https://www.covermymeds.com/main/insights/articles/a-brief-history-of-how-we-got-to-electronic-prior-authorization/

Prescription drugs (outpatient). Medicare.gov. Accessed October 15, 2021. https://www.medicare.gov/coverage/prescription-drugs-outpatient

Work closely with insurance companies to relieve financial assistance burdens and prior authorization requirements for patients.

Help Remove Barriers to Cost-Related Nonadherence

Jenny Peña, CPhT

Recognizing the valuable work of pharmacy technicians is a focus for the 

American Association of Pharmacy Technicians (AAPT). 

With National Pharmacy Technician Day 2021 on October 19, 

 offers a Scavenger Hunt to celebrate this special day and the pharmacy technicians who work hard to add value to their profession.

Pharmacy technicians from all practice settings are invited to play AAPT’s Scavenger Hunt. Technicians are asked to form a team of at least 3 pharmacy technicians with no cap for maximum number of team members. After naming their team, game participants check AAPT website at 

 each day for a listing of common and not so common items found in a pharmacy. 

Take a picture of at least one team member with the 'found' Scavenger Hunt item and post the picture to AAPT Facebook page. The first team to find all 10 Scavenger Hunt items with a picture wins. All Scavenger Hunt participants are entered in a $50 Amazon gift card drawing and $100 Amazon gift card awarded to the Scavenger Hunt winning team. Prizes will be awarded on Oct 20.

Ready. Set. Go!Scavenger Hunt item listing begins on Oct 8 and ends on Oct 18. Check for complete game details at 

With National Pharmacy Technician Day 2021 on October 19, AAPT Special Projects Team offers a Scavenger Hunt to celebrate this special day and the pharmacy technicians who work hard to add value to their profession.   

AAPT to Celebratbrate National Pharmacy Technician Day With Scavenger Hunt 

Judy Neville, CPhT

Although much work remains in addressing the underlying causes of social determinants of health (SDOH) in the country, health care systems have made great strides by examining the diversity and equity of staffing. During July’s 2022 Advanced Topics for Oncology Pharmacy Professionals Summit in San Diego, California, keynote speaker Vibhuti Arya Amirfar, PharmD, MPH, discussed dismantling racism by moving beyond the individual and addressing systemic structures allowing racism to continue, whether the cause be environmental, social, political, or otherwise. 

 attended this conference, with highlights covered on page 13 of this issue. A video interview with Amirfar—a global lead for gender equity and diversity workforce development for the International Pharmaceutical Federation based in The Hague, the Netherlands—is available at pharmacytimes.com.

In the cover feature on page 10, Justin Lindhorst, MBA, examines SDOH in the context of cancer treatment. He explains how this places specialty pharmacies at a critical point in addressing SDOH that may be contributing to cancer health disparities. Lindhorst discusses 5 actionable ways to address SDOH in specialty pharmacies and the potential impact of these interventions on patient health outcomes.

As part of addressing health equity, author Dea Belazi discusses trends in oncology pharmacy that are moving the field toward virtual care and a patient-focused approach to treatment (page 18). Belazi explains how more pharmacists are shifting to high-value, patient-focused roles in response to trends remodeling the market beginning in 2022. Belazi notes that these pharmacists will have a key impact in shaping the future of the field in a strategic way.

 (PTOE) welcomes its new editor in chief, Lisa E. Davis, PharmD, FCCP, BCPS, BCOP, who sits on PTOE’s editorial advisory board. With a background working in the early phase clinical trial and breast cancer programs at the University of Arizona Cancer Center, Davis brings a wealth of knowledge on research and practice areas relating to medication adherence, symptom management, drug development, drug resistance, and factors influencing anticancer drug disposition and response. Davis examines key points affecting the oncology pharmacy field in her first Editor’s Note for PTOE.

Health care systems have made great strides by examining the diversity and equity of staffing.

Oncology Pharmacists Renew Hope in Addressing Health Equity in Cancer Treatment

Mike Hennessy Jr, President and CEO

Hydroxychloroquine is an ineffective and potentially dangerous treatment for COVID-19, yet prescriptions for patients with the virus continue. Protecting people from this misguided therapy means pharmacists must take a stand and question the prescribed treatment.

When hydroxychloroquine came to the attention of the American public in 2020, it was commonly described as a malaria treatment. Besides being used to prevent malaria, it is often prescribed to treat autoimmune disorders including lupus and rheumatoid arthritis. Millions of Americans living with these chronic disorders depend on the drug to manage their symptoms.

Though it is approved for long-term use in autoimmune patients, hydroxychloroquine is a high-risk drug with well-known potential for adverse effects (AEs).

 Most AEs are mild and include headache, dizziness, and gastrointestinal distress.

In some patients, AEs are far more severe. Hydroxychloroquine is known to cause permanent changes to vision and hearing, suicidal thoughts, severe hypoglycemia, heart arrhythmia, and heart failure. Long-term patients on the drug are carefully monitored for early signs of toxicity.

During the spring of 2020, as the United States struggled to understand and contain the first wave of the COVID-19 pandemic, President Donald Trump touted the benefits of hydroxychloroquine in combating the virus, going so far as to say he took a preventative regimen himself. Trump’s optimism was rooted in anecdotal evidence and a few studies whose early results were inconclusive indicated that hydroxychloroquine might be effective against COVID-19.

When news of the drug’s potential hit the media, a frightened public clamored for it. The president’s endorsement further legitimized the treatment, though scientists, including Trump’s chief medical advisers, cautioned that its efficacy had not been proven.

Desperate for anything that might slow the virus’s assault, on March 20, 2020, the FDA briefly authorized using the nation’s emergency stockpile of hydroxychloroquine to treat COVID-19. Overwhelmed and underinformed physicians began doling out prescriptions for the drug, reasoning that doing anything, even if it had a chance of being ineffective, was better than telling patients they could do nothing.

More than half of the new prescriptions written in March and April 2020 came from primary care physicians. The number of new prescriptions from physicians who did not typically prescribe hydroxychloroquine surged from 1143 to 75,569 in the span of 1 month—an 80-fold increase from the year before.

The surge in prescriptions had 2 unintended consequences. First, the nation’s inventory of hydroxychloroquine quickly depleted. Autoimmune patients relying on the drug for long-term maintenance began rationing their pills as their prescriptions went unfilled.

Second, the rise in new patients led to a deluge of negative AEs. Within 3 months, the FDA MedWatch system received more than 10,000 reports of serious incidents, including deaths, involving hydroxychloroquine.

For 12 frenzied weeks, hydroxychloroquine flew out of pharmacies. Meanwhile, studies on the drug’s efficacy against COVID-19 continued—and the results were not good. The amount of data showing the drug might be effective in treating the virus were overshadowed by data indicating it was ineffective at best and harmful at worst.

“The FDA determined that chloroquine and hydroxychloroquine are unlikely to be effective in treating COVID-19,” the FDA said in a June 15 news release revoking the emergency use authorization (EUA). “In light of ongoing serious cardiac adverse effects and other potential serious side effects, the known and potential benefits of chloroquine and hydroxychloroquine no longer outweigh the known and potential risks.”

State boards of pharmacy across the nation followed the federal agency’s lead, issuing policies that ranged from advising caution to restricting prescriptions to a 14-day supply only to those with a positive diagnostic test.

Since the EUA was revoked, the rate of hydroxychloroquine prescription has dropped significantly, but it has not yet reached pre-COVID-19 levels. As the pandemic drags on and new virus variants surface, some physicians continue to prescribe the drug in the mistaken belief that it offers patients their best chance of recovery.

Pharmacists have 3 primary roles in public health: first responder, consultant, and medical partner. The ongoing debate about hydroxychloroquine and COVID-19 requires pharmacists to step into that third role and take responsibility for their patients’ welfare.

Pharmacists are not order-takers for physicians. They are partners collaborating with other health care professionals to get patients the treatment they need.

The pharmacist is the last barrier between a patient and a drug. That is why it is so critical for pharmacists check for allergies, potential drug interactions, patient understanding of how to use the drug, and whether the prescription is appropriate for the diagnosis. The pharmacist who dispenses a drug to the patient is ultimately responsible for that patient’s welfare.

A prescription for an off-label use of a drug, such as using hydroxychloroquine to treat COVID-19, should trigger a red flag, particularly when the drug comes with such high risks. Before filling that prescription, a responsible pharmacist will contact the prescribing doctor to confirm the diagnosis and the treatment plan.

Physicians who do not routinely treat patients for autoimmune disorders may be unfamiliar with which medications conflict with hydroxychloroquine or with patient risk factors that increase the chances of AEs.

Physicians may be unaware of the latest studies on the drug’s efficacy in treating COVID-19. Physicians are also unlikely to realize that off-label use of hydroxychloroquine is rarely covered by insurance, leaving patients to pay out-of-pocket for this expensive and ineffective treatment.

Pharmacists are often hesitant to question a physician’s prescribed regimen for fear of pushback.

But this call does not have to be combative, both the physician and the pharmacist ultimately have the patient’s best interests at heart. The call is an opportunity for the pharmacist to discuss the risks and potential benefits of the prescribed drug with the physician.

The pharmacist is the last barrier between a patient and a drug, which is why it's critical for pharmacists to check for allergies, potential drug interactions, patient understanding of how to use the drug, and whether the prescription is appropriate for the diagnosis. 

Authors