Oral chemotherapy agents (OCAs) have significantly altered the provision of cancer therapy, allowing cancer to be managed as a chronic condition within the patient’s home. Despite the established place of these drugs in the care continuum, managing oral oncolytics requires unique strategies compared with infusion therapies, including timely coordination among oncology providers, clinical pharmacists, dispensing pharmacies, and the patient.

OCAs, such as chlorambucil, cyclophosphamide, methotrexate, and 6-mercaptopurine, have been available for decades; however, the major expansion and growth in oral oncology can be traced to the late 1990s with FDA approval of capecitabine.1 OCAs offer several advantages over the parenteral route, including improved patient convenience, increased flexibility in timing and location of administration, and a better quality of life. As a result of rapid expansion, personalized medicine, the emergence of targeted therapies, and the increasing involvement of pharmacists in OCA management, several guidelines have been published aiming to optimize care.2-4 A list of chemotherapy and OCA guidelines is included in SIDEBAR 1.2-5

Adhering to published guidance is crucial to proper management of OCAs. In addition to developing a comprehensive understanding of the benefits and risks of these drugs, pharmacists must ensure patients’ access to OCAs and provide appropriate education and training to guarantee safe use.

Measuring the Value of OCAs

Benefits

OCAs are a popular treatment option for patients due to their convenience; in addition, select OCAs provide novel treatment modalities and improved outcomes. OCAs permit patients to receive cancer therapies without the need for central access, infusion appointments, or coordination of work schedules.

Recent shifts from IV chemotherapies to OCAs present multiple opportunities to improve the prescribing, dispensing, administering, and monitoring processes for OCAs.4 However, the rising costs of targeted OCAs has led to several hurdles oncology practices must overcome to acquire these medications for patients in a timely manner. To properly manage OCAs, pharmacists must have a clear understanding of the key considerations for safe and optimal use in practice.

Risks

Despite their established place in cancer care, OCAs are associated with a variety of safety concerns for the patient and the care team, including the following:

Patient Selection. Only appropriate patients should be prescribed OCAs. It is important to note that patients for whom OCAs are an option must be able to adhere to complex regimens and self-monitor potential complications and adverse drug reactions (ADRs).1 Regimens may be as simple as taking an OCA once daily over time to as complicated as taking an OCA twice daily on days 1-5 and 8-12, every 28 days. In addition, consider that patients often may be taking several therapies for other chronic conditions and/or symptom management, and must be competent to take all their medications correctly. The patient must agree to coordinate with their care team and the dispensing pharmacy in a timely manner regarding labs and follow-up appointments, refills, and any ADRs. Finally, note that patients receiving cancer therapies are often elderly and may experience chemo brain, resulting in difficulty remembering how and when to take their medications. Therefore, identifying patients who will be compliant and adherent to therapy is crucial for safe use.

Safe Handling Concerns. OCA handling presents significant risk. Detailed education should be delivered at treatment initiation to minimize the potential for harm from these cancer therapies within the patient’s home. Particular attention should be given to the proper disposal methods.4 SIDEBAR 2 presents tips for safe OCA handling in the patient’s home.

Complex Processes. Other risks associated with OCAs may arise within oncology practices as a result of the complex processes required for managing these medications. For example, prescription writing and miscommunication with the pharmacy have historically been identified as major challenges.6 Institutions should have policies in place outlining safe OCA prescribing. Policies should include a clinical assessment by a pharmacist of the OCA prescribed (including drug-drug interactions, dose and indication verification, and labs and drug-specific monitoring), patient education, and coordination of care. A direct line of communication should be established between providers and pharmacists to ensure safe and timely initiation of therapy. A triage system will help facilitate financial procurement. Additionally, institutions may consider “firewalls” within the EMR to identify OCAs that have not been vetted through a pharmacist.

OCA Access. The lack of a medically integrated pharmacy—ie, a specialty pharmacy, able to dispense oral oncolytics from the provider practice—results in major barriers for oncology practices. For example, without such a pharmacy, the coordination of labs and follow up must be completed much earlier than subsequent cycle start dates so that patients can receive their medications within a timely manner from the mail-order pharmacy. These practice gaps, which often result from payer requirements to use a mail-order pharmacy, can lead to increased spending, waste, and unsafe practices or delays in care, increasing the overall risks of oral chemotherapy. A recent study demonstrated that a medically integrated pharmacy is able to significantly minimize annual costs by reducing waste.7

Comparing Dispensing Models

Medically Integrated Pharmacies

To ensure patients can access OCAs, it is important to discern the differences between medically integrated pharmacies and mail-order pharmacies. Provider practices that have a medically integrated pharmacy are able to supply a prescription to the patient quickly, often within the hour. Typically, coordination between a provider and a medically integrated pharmacy is seamless. Pharmacists within a medically integrated pharmacy have access to the EMR and are able to view medication changes, assess labs, review provider appointments, and communicate actively with the patient. Additionally, practices that have a medically integrated pharmacy allow for patient follow-up closer to the start time of a subsequent cycle, for a better assessment of recovery, symptom management and control, and assessing compliance of the full cycle. The patient typically receives all services within the same day. Additional information on the value of medically integrated pharmacy can be found through the National Community Oncology Dispensing Association (NCODA).8 (More information about NCODA is included in SIDEBAR 3.)

Mail-Order Pharmacies

In contrast, mail-order pharmacies require coordination of mail delivery and do not have access to the EMR. The primary motivation behind utilizing a mail-order pharmacy often stems from payer restrictions. The prolonged coordination required to get the prescription to the patient may force providers to send in new prescriptions prior to seeing the patient or their lab results. However, upon follow-up, dose reductions or cycle delays may be indicated, despite the patient having already received their next cycle from the mail-order pharmacy.

The lack of integration between oncology practices and mail-order pharmacies is a major barrier to effective OCA management. Although mail-order pharmacies play a significant role in maintenance therapies for non-oncologic indications and may help minimize cost, the high acuity and monitoring needed for patients with cancer often does not align with mail-order dispensing.

The Role of the Pharmacist in OCA Management

Regardless of the dispensing model used to provide patients with OCAs, pharmacists play an integral role in establishing optimal care through safe prescribing, dispensing, administration, monitoring, and education. A clinical oncology pharmacist should be a part of oncology care teams that prescribe OCAs.

Prescribing

The OCA prescribing process varies significantly among practices and different EMR systems. Potential variations include the way the initial and subsequent prescriptions are written, the length of therapy dispensed, the number of refills (if any), and the selection of the pharmacy to provide the prescription. Pharmacists can safeguard optimal OCA prescribing through assessment of clinical appropriateness based on indication and dose, organ function, and drug-drug interactions (DDIs).

Prescribing one cycle of chemotherapy at a time, with no refills, is an accepted, safe practice that makes certain appropriate monitoring takes place with each cycle of treatment. Pharmacists should confirm that this practice occurs, assess patients in between cycles, and certify that the correct cycle length and number of pills are dispensed based on dose, missed doses, and dose reductions, etc. Additionally, clinic pharmacists should ensure that prescriptions are routed to the correct dispensing pharmacy to avoid potential delays in care.

Dispensing

Dispensing OCAs can involve extensive coordination. Most therapies will require some form of benefits investigation upon initiation of therapy, including prior authorizations, financial assistance, free-drug programs, copay cards, and more. The pharmacist, together with a financial coordinator, is responsible for timely financial procurement and treatment initiation. Benefits investigation may also be required upon patient employment changes and at the start of each new year. Early coordination and communication with patients is critical to prevent treatment delays.

Some OCAs, such as immunomodulatory drugs panobinostat, idelalisib, and duvelisib, may require specific elements of a Risk Evaluation and Mitigation Strategies (REMS) program. To search for REMS by drug name, visit https://www.nccn.org/rems. Pharmacists are responsible for confirming that REMS requirements are met, in addition to dispensing the therapies in a safe and timely manner. Clinic pharmacists should work directly with patients, care teams, and mail-order pharmacies to guarantee that medications reach the patients in a timely manner.

Oral Chemotherapy Education

Education and direct communication with patients are necessary to allow the patient to handle and administer the OCA safely at home. In addition, the pharmacist will assess ADRs, evaluate medication changes, monitor adherence/compliance, coordinate labs and follow up, and communicate issues with providers.

As a critical component of OCA management, patient education must occur prior to initiating therapy. However, not all organizations have comprehensive OCA education plans in place. Spearheaded by NCODA, several organizations, including the Association of Community Cancer Centers, the Hematology/Oncology Pharmacy Association, and the Oncology Nursing Society, have partnered to develop a non-branded, educational resource for patients receiving OCAs.9 These oral chemotherapy education sheets are designed for the patient and highlight proper administration, handling, and symptom management. The documents outline if medications should be taken with or without food, how to handle missed doses, and drug-food interactions. In addition, to minimize patient exposure, safe handling and disposal are discussed. The oral chemotherapy education sheets also highlight ADRs that occur in ≥30% of patients and provide specific interventions to manage symptoms, including when to seek medical attention.

The sheets provide significant value, as they are maintained and kept up-to-date by the aforementioned organizations. Often, with the rapid growth in hematology/oncology practices, health systems lack the resources to develop and update internal education material.

Pharmacists can also identify complications through literature sources and DDI databases.10 Adherence/compliance tools (eg, pill diaries, pill counts, electronic medication monitors, apps, prescription refill rates, biological assays) should be tailored to the needs of the patient.4 New technology referred to as digital pills, which transmit from inside the stomach to portable devices whenever patients take their medication, are being trialed to help improve adherence/compliance and safety of OCAs.11

Oral Chemotherapy Training

In addition to pharmacists, other personnel may be involved in OCA dispensing and management, including financial counselors, care coordinators, nurses, residents, and students. All personnel should be trained in the OCA dispensing process so that they have a solid foundation in handling issues that may arise or know how to triage those issues.

Financial coordinators should have adequate training in medical terminology and navigating the EMR, as they often initiate the prior authorization and paperwork required to procure OCAs. Financial coordinators should be equipped with tools to guide them in seeking copay assistance through foundations and manufacturer programs and be able to navigate various resources for financial support. Some of these resources may be found through the NCODA Financial Assistance Tool (which provides up-to-date, comprehensive financial resources about chemotherapy options, available at: http://www.ncoda.org/financial-assistance-p)12 Applications for select therapies may ask disease-specific questions about cytogenetics, mutations, and prior lines of therapy. Pharmacists and clinicians should serve as additional resources to help answer clinical questions outside the scope of expertise of the financial coordinator.

OCA management programs should have processes in place to highlight patient follow-up assessments, coordination of care, and responsible personnel. Upon treatment initiation, frequent follow-up calls or check-ins should be conducted to confirm that patients are not experiencing any unexpected side effects. Patient follow-up can occur via phone, email, or in person, and be conducted by a pharmacist, nurse, resident, or intern (under the supervision of a professional). Coordination of care among the care team and the patient should include timely clinic follow-up and appropriate lab assessments of hematologic parameters, organ function, and any drug-specific monitoring. Follow-up assessments should, at minimum, evaluate cycle start dates, adherence/compliance, refill dates, safety, and appointment reminders.

Conclusion

OCAs have expanded the armamentarium of cancer treatment in ways not possible through infusion therapies alone, providing new approaches and modalities to treat various types of cancer and have transitioned cancer treatments into a chronic disease model. However, despite proven efficacy, oral chemotherapy processes still pose tremendous work for care teams due to payer restrictions, cost, the limitations of mail-order pharmacies, and patient follow-up.

Pharmacists play a crucial role on the care team in ensuring safe, proper use of OCAs to optimize patient outcomes. Workflows should be continually evolving as they are adapted and improved to optimize prescribing, dispensing, education, monitoring, and follow-up for all patients receiving OCAs.

Kirollos S. Hanna, PharmD, BCPS, BCOP, is an assistant professor of pharmacy at the Mayo Clinic College of Medicine and a hematology and oncology clinical pharmacist at Mayo Clinic and the University of Minnesota Medical Center in Minneapolis, Minnesota. He received his doctorate from Florida A&M University and completed a PGY1 residency at St. Thomas Hospital in Nashville, Tennessee, and a PGY2 residency in oncology at St. Luke’s Mountain States Tumor Institute in Boise, Idaho. Kirollos serves on the Executive Council for the National Oncology Community Dispensing Association and is an active member and has been an invited speaker for NCODA, HOPA, and MSHP.

References

1. Weingart SN, Brown E, Bach PB, et al. NCCN Task Force Report: Oral chemotherapy. J Natl Compr Canc Netw. 2008;6 suppl 3:S1-S14.
2. Neuss MN, Gilmore TR, Belderson KM, et al. 2016 Updated American Society of Clinical Oncology/Oncology Nursing Society chemotherapy administration safety standards, including standards for pediatric oncology. J Oncol Pract. 2016;12(12):1262-1271.
3. Goldspiel B, Hoffman JM, Griffith NL, et al. ASHP Guidelines on Preventing Medication Errors With Chemotherapy and Biotherapy. Am J Health-Syst Pharm. 2015;72(8):e6-e35.
4. Mackler E, Segal EM, Muluneh B, et al. 2018 Hematology/Oncology Pharmacist Association Best Practices for the Management of Oral Oncolytic Therapy: Pharmacy Practice Standard. J Oncol Pract. 2019;15(4):e346-e355.
5. NCODA Press Release: ASCO/NCODA Oral Chemotherapy Dispensing Standards Initiative. www.ncoda.org/docs/asco-ncoda-oral-chemotherapy-dispensing-standards-initiative/. Accessed May 7, 2019.
6. Weingart SN, Spencer J, Buia S, et al. Medication safety of five oral chemotherapies: A proactive risk assessment. J Oncol Pract. 2011;7(1):2-6.
7. Howard A, Kerr J, Mclain M, et al. Financial impact from in-office dispensing of oral chemotherapy. J Oncol Pharm Pract. 2018;1078155218799853.
8. Wimbiscus B. Medically Integrated Dispensing: An Alternative to How Oral Drugs Get Dispensed. AJMC. www.ajmc.com/contributor/ncoda/2019/03/medically-integrated-dispensing-an-alternative-to-how-oral-drugs-get-dispensed. Accessed May 7, 2019.
9. Oral Chemotherapy Education Sheets. http://oralchemoedsheets.com/
10. Rogala BG, Charpentier MM, Nguyen MK, et al. Oral anticancer therapy: Management of drug interactions. J Oncol Pract. 2019;15(2):81-90.
11. Hanna, KS. Expert Opinion: Digital Pills May Be on the Horizon in Cancer Care. OncLive. 2019; 20(5). www.onclive.com/publications/oncology-live/2019/vol-20-no-5/digital-pills-may-be-on-the-horizon-in-cancer-care.
12. NCODA Financial Assistance Tools. www.ncoda.org/financial-assistance-p. Accessed May 7, 2019.

SIDEBAR 1

Guidelines for Managing Chemotherapy and Oral Oncolytics

• American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) Safety Standards2: tinyurl.com/y6gsw7rl. Additional information is available at: www.asco.org/chemo-standards.
• American Society of Health System Pharmacists (ASHP) Guidelines on Preventing Medication Errors With Chemotherapy and Biotherapy3: https://academic.oup.com/ajhp/article/72/8/e6/5111768.
• Hematology/Oncology Pharmacist Association (HOPA) Best Practices for the Management of Oral Oncolytic Therapy: Pharmacy Practice Standard4: tinyurl.com/y6dyn7j4

In addition, the National Community Oncology Dispensing Association (NCODA) and ASCO are currently in the process of drafting oral chemotherapy dispensing standards.5