Oral cancer agents (OCAs) are used to treat a wide variety of malignancies (see TABLE 1), and robust drug development in this category continues to spur increased use of these medications. The Food and Drug Administration (FDA) has approved 44 OCAs in the last decade (see TABLE 2 on page 17),1 and there are now over 50 OCAs approved for use in the United States.2 Approximately 25% to 30% of new cancer drugs in development are OCAs.2
Distinct advantages exist when comparing OCAs to the traditional intravenous (IV) formulation anti-cancer agents. Patients who receive OCAs often report a greater sense of control over their treatment, less interference with daily work and social activities, reduced travel time and costs, and the elimination of discomfort associated with an IV line. Conversely, OCAs also present unique challenges, including the possibility of a significant medication error if a patient does not understand administration instructions; lack of patient adherence with more complicated regimens (take for x days, then stop for x days, etc) potentially leading to over- or under-dosing; intensive monitoring requirements, special handling, and disposal requirements; as well as coverage and cost concerns. It is important to keep in mind that the use of OCAs also requires significant dedicated resources on the part of the provider—eg, comprehensive and ongoing education, effective monitoring, and assistance with access—services that are currently not reimbursable. Therefore, developing a comprehensive OCA management plan and utilizing guidance from published resources is critical to ensure the effective and safe use of these medications.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (The James) in Columbus, Ohio, one of only 46 National Cancer Institute (NCI)-designated comprehensive cancer centers in the nation, has earned NCI’s highest ranking by providing exceptional cancer care. Aligned with a nationally ranked academic medical center and a freestanding cancer hospital on the campus of one of the nation’s largest public universities, The James’ vision is to eradicate cancer through research that translates to innovative, highly targeted patient care. Utilizing a multidisciplinary, multimodal approach to cancer treatment, The James is a founding member of the National Comprehensive Cancer Network (NCCN), an organization that publishes national guidelines and standards of care for patients with cancer.
The safe use of OCAs in patients for whom these medications are indicated is a primary concern of The James pharmacy department. Ensuring OCA safety requires a comprehensive approach to prescribing, dispensing, administering, monitoring, and storing and handling these medications, in addition to effective staff and patient education. Moreover, coverage and cost concerns, as well as developing and implementing appropriate policies and procedures (P&Ps) for OCA use, are critically important.
Recommendations for Safe Use of OCAs
Prior to prescribing an OCA, it is important to assess whether the patient can swallow the medication and is competent to self-administer the medication. Pharmacists should assess the clinical appropriateness of the OCA ordered based on the disease and patient-specific characteristics. The need for supportive care medications should be assessed and these should be prescribed in tandem if needed. Standardized orders sets should be utilized (ie, CPOE, electronic templates, or pre-printed order forms) with the generic drug names. OCAs should be included in the IV chemotherapy treatment plan when given in combination so all care providers are aware that the patient is receiving both oral and IV therapy. Handwritten and called-in prescriptions (except to hold or discontinue treatment) should not be permitted. All prescriptions for OCAs should include: diagnosis, height, weight, BSA, prescribed dose, total daily dose, start/stop dates, and cycle number. Patients should be assessed for financial ability to obtain the medication and referred to assistance as needed. Finally, OCAs should be added to the home medication list kept by the provider and medication reconciliation should be performed.
The number of dosage forms and concentrations that are needed for each prescription should be minimized to help avoid medication errors. Medication reconciliation and an independent double-check should be completed with each dispense. Bar code scanning should be utilized during the dispensing process, and OCAs should be added to the home medication list kept by the dispensing pharmacy. It is imperative that clear, specific directions are used to ensure patients take OCAs correctly—ie, the number of tablets of each strength to be taken. Use as directed should never be stated on a prescription label.
Patients should be instructed not to crush or chew tablets, and to immediately wash their hands after taking OCAs or to wear gloves when taking the tablets. Dose adjustments should not occur unless directed by the physician. Unused medication should be returned to the pharmacy for appropriate disposal. (See SIDEBAR 1. Recommendations for Patients and Caregivers.3)
Because OCAs are taken in the patient’s home, strategies for monitoring patients must be modified to ensure the patient can safely and effectively take the medication in the home environment. The patient’s treatment plan should include the frequency of office visits for follow-up and specific monitoring requirements. Follow-up phone calls (performed by a pharmacist or nurse) should be utilized between office visits and probing questions should be asked to monitor for adherence and toxicities.
Patients should be encouraged to keep medication journals/calendars to record medication adherence and toxicities for evaluation at each visit. The importance of adherence should be reinforced at each office visit and every touchpoint with the patient. Changes to the patient’s financial situation should be assessed at each visit to avoid challenges related to medication access.
Storage and Handling
In the hospital, cytotoxic drugs should be stored in a designated area and separate from non-cytotoxic agents. An updated list of hazardous medications should be kept readily available. Staff who may come into contact with cytotoxic OCAs should undergo appropriate training and education on the risks associated with their handling. Personal protective equipment (PPE) should be made available for use when handling OCAs to minimize exposure and health risks. Hands should be washed before and after donning gloves, and PPE should be disposed as cytotoxic waste.
Automated counting machines should not be used for OCAs. Non-disposable items (eg, counting trays, tools, surfaces, etc) should be washed or decontaminated thoroughly. Separate equipment and a separate counting area should be used for cytotoxic and non-cytotoxic agents. Agents in powder form should be prepared in the pharmacy, and oral liquid doses should be placed in an oral syringe in the pharmacy (when possible). A written emergency plan should be developed for accidental spills or exposure, and drills should be conducted to ensure staff competency. Exposure to cytotoxic agents by pregnant staff should minimized or eliminated.
Safe use of OCAs is contingent upon appropriate, routine, and consistent staff education. A primary educator should be designated to assume ownership of the process. The staff education plan should be specific for each health care professional’s role and include a review of: medications (indications, dosing, side effects, etc), safe handling and disposal, available patient education materials, assessing/monitoring adherence, cost and access issues (eg, specialty pharmacies, prior authorization, manufacturer and copay assistance programs), and documentation requirements. Checklists can be useful to remind staff of the key elements required for effective staff education, and policies and procedures should be developed and maintained to support safe practice guidelines.
Effective patient education is central to ensuring medication adherence and safety when using OCAs. It is important to note that although OCAs offer patients convenience and increased control over their treatment, they are not appropriate for every patient. When considering an OCA for a patient, be aware of the following barriers to adherence: a complex drug regimen, patient diagnosed with multiple chronic conditions, psychological problems (eg, depression), age and possible cognitive impairment, lack of social and family support, low literacy level, and a history of inadequate follow-up.4
Patients prescribed OCAs should receive both written and verbal instructions. Printed educational materials should include:
Including the patient’s family and caregivers in the education process can be useful, depending on the patient’s ability to assume responsibility for managing therapy. Follow-up phone calls should be made to ensure prescriptions have been filled, assess understanding, and answer questions. At each patient visit, adherence, treatment tolerance, and adverse events should be assessed. Patients should be encouraged to bring medication bottles with them to their appointments, report any medication errors (took too few or too many doses, etc), and discuss any access or cost issues (eg, specialty pharmacies, prior authorization, manufacturer and copay assistance programs).
Coverage and Cost Concerns for OCAs
According to the Hematology/Oncology Pharmacy Association (HOPA),5 financial disparities between OCAs and IV chemotherapy cost and reimbursement can create barriers to patient’s receiving OCAs, even when they are the most appropriate treatment for the patients’ diagnosis (see SIDEBAR 2. OCA Parity Legislation).6-7 The financial constraints imposed by high out-of-pocket expenses can force patients to choose an alternative IV treatment, which may not be the most effective therapy for their specific cancer, or even force patients to abandon therapy. Statistics indicate that ~10% of patients receiving OCAs abandon them,8 and patients with >$200 per month in out-of-pocket costs are three times more likely not to fill their prescriptions.9
Robust OCA management is contingent upon various factors; perhaps the most significant is investing in the necessary infrastructure and staff to ensure medication access support. OCA copays can be high, and obtaining prior authorization—which is typically required—can be challenging and time consuming. At The James, we have found that ensuring patient access to OCAs is vital, requiring dedicated, experienced, and knowledgeable staff. The sole responsibility of these staff is to assuage coverage and cost concerns by providing patients with copay and manufacturer assistance at multiple sites within the health system.
Medication Access Considerations
Some insurance plans disadvantage OCAs by placing them into the specialty tier benefit of the prescription program or excluding the product all together. This results in decreased drug costs for the payer at the expense of the patient, who must then pay high out-of-pocket copays. Thus, verifying a patient’s prescription coverage is critical prior to including an OCA as part of the patient’s treatment plan.
Medication Assistance Programs
Medication assistance programs have been useful in alleviating some of the cost concerns for both oral and IV chemotherapy. Copay assistance is available to reduce out-of-pocket copays for non-governmental insured patients for both IV and oral medications. Disease-based assistance is available through non-profit grants for both governmental insured patients (eg, Medicare patients) and commercially insured patients to cover the cost of copays for specific medications used in specific disease states. It is important to note that the sustainability of such programs is uncertain. It is not uncommon for a patient to receive assistance from a non-profit copay assistance organization only to have that organization run out of money after a period of time. If this occurs, assistance can be sought from the pharmaceutical manufacturer in the form of free medication when/if the patient meets specific criteria. Moreover, while some patients qualify for reduced copays and assistance funds as stopgap measures to ensure OCA access, these measures cannot meet the needs of all patients, and some payers actually prohibit their use (the most commonly seen is prohibition of copay card use).
Prior Authorization and Mail-Order Pharmacy Delays
Most OCAs require prior authorization, which can lead to treatment delays. Obtaining prior authorization for patients is a time-consuming task that requires experienced, knowledgeable staff and access to patient-specific clinical information. Delays are common when patients are required to obtain their medication through a mail order or specialty pharmacy, not affiliated with their oncology provider, versus obtaining their medication directly from the onsite health-system owned specialty pharmacy provider. Onsite staff has immediate access to patient medical records to obtain the required information and to the patient care providers should any of the prescription information require clarification.
The Role of Specialty Pharmacy
To overcome many of the obstacles to OCA adherence and access, including appropriate monitoring and management of the patient, many hospitals have opened or are considering opening their own specialty pharmacies. To ensure that patients at The James receive timely access to OCAs and other specialty medications, the pharmacy department opened its own specialty pharmacy in 2014. The goal of this pharmacy is to improve continuity of care for cancer patients and other patients who receive specialized medications. Patients receive customized monitoring, tailored to their personal and medication related needs. Since opening, the pharmacy has improved patient access (assuming the payer allows the pharmacy in their network), adherence, accuracy of the medical record, and screening for drug interactions. Prescribing physicians have been especially pleased with ease of access to and timely receipt of medications.
One of the most significant considerations moving forward is the patient’s ability to afford these medications, especially given the uncertainty of some of the patient support programs. In the absence of health care reform addressing the issue or OCAs being moved under the medical benefit to ensure parity, the most reasonable solution is for oral parity legislation at the federal rather than the state level. State legislation only impacts individual health plans funded by the state and state employee plans. Federal legislation, such as the Cancer Drug Coverage Parity Act,7 would apply to all private health insurance plans, benefiting those who are on ERISA-regulated plans as well as existing individual group plans.
Given the current health care environment, the number of underinsured patients is outpacing the number of uninsured patients. These underinsured patients will continue to challenge our ability to provide OCAs for all patients for which they are the best treatment option.
As OCA development continues its frenetic pace, patients with cancer have ever-increasing treatment options. While OCAs have clear benefits, proper management is crucial to safe use. Investing the necessary time and resources in an OCA management program ensures that patients for whom these medications are indicated can access them and benefit from their use.
Niesha Griffith, MS, RPh, FASHP, is vice president, cancer services, for WVU Medicine, where she is responsible for providing overall direction with regard to the strategic, operational, clinical, financial, and administrative functions associated with cancer services. Prior to coming to WVU, Niesha was administrator for pharmacy and infusion services at The James Cancer Hospital at The Ohio State University (OSU).
Julie Kennerly, PharmD, MS, BCPS, is assistant director, pharmacy, for The James Cancer Hospital, where she is responsible for hematology/oncology, pain and palliative, and ambulatory care clinical services. Julie has successfully implemented two hospital-based pharmacies that dispense both specialty and non-specialty medications.
Sarah Hudson-DiSalle, RPh, PharmD, is the manager of the medication assistance program and reimbursement services at The James Cancer Hospital, where she has been successful in the development of services aimed at improving access to medications across the OSU system.
Recommendations for Patients and Caregivers3
“Dos” for Oral Chemotherapy
“Don’ts” for Oral Chemotherapy
OCA Parity Legislation
Oral chemotherapy parity legislation is designed to ensure equal coverage for oral and IV chemotherapy drugs. As of July 2016, 42 states plus the District of Columbia have enacted oral chemotherapy access laws (see FIGURE 1).6 Efforts to pass Ohio SB 194, the Cancer Treatment Modernization Bill, were led by The James pharmacy leaders.
To date, no federal legislation has passed to ensure equal access to OCAs. HR 2739: The Cancer Drug Coverage Parity Act, introduced in June 2015, would require any health plan that provides coverage for cancer chemotherapy treatment to provide coverage for self-administered anticancer medication at a cost that is no less favorable than the cost of IV, port-administered, or injected anticancer drugs.6-7 The bill has not yet passed the House or Senate.
Suggested Reading List
ASHP Guidelines for Handling of Hazardous Drugs. http://www.ashp.org/DocLibrary/BestPractices/PrepGdlHazDrugs.aspx. Accessed December 12, 2016.
Jacobson JO, Polovich M, McNiff KK, et al. American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards. Oncol Nurs Forum. 2009;36(6):651-658.
Neuss MN, Polovich M, McNiff K, et al. 2013 Updated American Society of Clinical Oncology/Oncology Nursing Society Chemotherapy Administration Safety Standards Including Standards for the Safe Administration and Management of Oral Chemotherapy. Onc Nurs Forum. 2013;40(3):225-233.
https://www.ons.org/sites/default/files/2013chemostandards.pdf. Accessed December 12, 2016.
Other Published Guidelines
Guidelines for the Safe Prescribing, Dispensing and Administration of Cancer Chemotherapy; a consultative report prepared by Clinical Oncological Society of Australia, November 2008. https://www.cosa.org.au/media/1093/cosa_guidelines_safeprescribingchemo2008.pdf. Accessed December 12, 2016.
National Patient Safety Agency. Oral anti-cancer medicines: risks of incorrect dosing. NPSA/2008/RRR001. http://www.nrls.npsa.nhs.uk/resources/?entryid45=59880. Accessed December 12, 2016.
The Society of Hospital Pharmacist of Australia Committee of Specialty Practice in Cancer Services. Standards of Practice for the Provision of Oral Chemotherapy for the Treatment of Cancer. J Pharm Pract Res. 2007;37(2):149-152.
Weingart SN, Flug J, Brouillard D, et al. Oral chemotherapy safety practices at US cancer centres: questionnaire survey. BMJ. 2007;334(7590):407.
Weingart S, Spencer J, Buia S, et al. Medication safety of five oral chemotherapies: a proactive risk assessment. J Oncol Pract. 2011;7(1)1:2-6.
Bernard DS, Farr SL, Fang Z. National estimates of out-of-pocket health care expenditure burdens among nonelderly adults with cancer. J Clin Oncol. 2011;29(20):2821-2826.
Gleason PP, Starner CI, Gunderson BW, et al. Association of prescription abandonment with cost share for high-cost specialty pharmacy medications. J Manag Care Pharm. 2009;15(8):648-658.
Streeter SB, Schwartzberg L, Husain N, et al. Patient and plan characteristics affecting abandonment of oral oncolytic prescriptions. Oncol Pract. 2011;7(suppl 3):46S-51S.
Barton D. Oral agents in cancer treatment: the context for adherence. Semin Oncol Nurs. 2011;27(2):104-115.
Landier W, Hughes CB, Calvillo ER, et al. A grounded theory of the process of adherence to oral chemotherapy in Hispanic and Caucasian children and adolescents with acute lymphoblastic leukemia. J Pediatr Oncol Nurs. 2011;28(4):203-223.
Phillips B, Richards M, Boys R, et al. A home-based maintenance therapy program for acute lymphoblastic leukemia – practical and safe? J Pediatr Hematol Oncol. 2011;33(6):433-436.
Spoelstra SL, Given CW. Assessment and measurement of adherence to oral antineoplastic agents. Semin Oncol Nurs. 2011;27(2):116-132.
Streeter SB, Schwartzberg L, Husain N, et al. Patient and plan characteristics affecting abandonment of oral oncolytic prescriptions. Am J Manag Care. 2011;17(suppl 5):SP38-SP44.
Timmers L, Boons CC, Mangnus D, et al. The use of erlotinib in daily practice: a study on adherence and patients experiences. BMC Cancer. 2011;11:284.
Winterhalder R, Hoesli P, Delmore G, et al. Self-reported compliance with capecitabine: findings from a prospective cohort analysis. Oncology. 2011;80(1-2):29-33.
Wood L. A review on adherence management in patients on oral cancer therapies. Eur J Oncol Nurs. 2012;16(4):432-438.
Association of Community Cancer Centers Resource. Steps to Success: Implementing Oral Oncolytics. (Funding and Support Provided by Pfizer Oncology.) http://resources.accc-cancer.org/oral-oncolytics/about-this-project/. Accessed December 12, 2016.