Oral therapies for cancer: a boon for treatment and bane for adherence

Oral therapies have revolutionized cancer treatment with their ease of administration.
However, they are prone to non-adherence as drugs are administered by patients away from health care settings¹.
Cancer therapies are now akin to treatments for chronic ailments, lasting for several years. Therefore, the medication adherence barriers that pertain to chronic disease have become significant in cancer management^2,3.

Cancer is among the leading cause of death across the globe. More than 18 million new cases were diagnosed in the year 2018⁴, which is set to reach 29.4 million by 2040 (source: The cancer Atlas)⁵. The change in world demography due to high life expectancy is expected to further fuel cancer incidences. The technological and pharmaceutical advances have resulted in a better 5-year relative survival for cancer patients⁶. As per SEER registry data from the United States, survival for cancer patients has improved from 50% to upto 68% by 2020⁷. Therefore, more patients are now dependent on anti-cancer medication either for reducing the tumor size or for protection from a future relapse, that too for longer periods. Cancer has become similar to chronic diseases in its outlook³. Non-adherence to oral medication for cancer treatment has become a major issue with the increasing use of oral anticancer drugs for cancer treatment^1,2.

Challenges for adherence in Cancer therapy

Cancer patients are thought to be generally adherent to medication due to the impact of disease on survival, but reports show it is otherwise³. The last two decades have seen a steep rise in the approval of oral therapies for cancer and an increase in their prescription¹. With this, the onus of administering medicines has shifted to patients rather than medical professionals⁸. Several cancers like ovarian, breast, prostate, leukemia, and lymphomas are comparable to chronic diseases in their long-term nature with patients expected to use cancer medications for several years for either protection or treatment². It has led to a change in attitude toward cancer medication resulting in non-adherence ranging from 40 – 100% in cancer patients⁹.

Most robust non-adherence data is available for breast cancer that shows an alarmingly low rate of adherence (50%) for adjuvant hormone therapy owing to adverse effects and the long-term usage¹⁰. Similar to other chronic diseases, barriers for non-adherence to cancer therapies can be largely grouped into three categories – therapy-related, healthcare-related, and patient-related, discussed below in detail.

A. Therapy-related factors

The complexity of the dosage regimen: Oral therapy for cancer is often complex, with a period of active administration followed by a deliberate inactive period when no drug is taken to reduce the cytotoxic effects of the drug. Additionally, multiple drugs may be required to be administered in an overlapping or completely different schedule. This is often a cause of confusion among patients leading to incomplete dosage or inappropriate dosage¹¹.
Enhanced adverse effects: Cancer therapy often does not differentiate between cancerous and healthy cells leading to severe adverse effects⁸. These adverse effects are major deterrents to therapy. For example, one-fourth of breast cancer patients are intentionally non-adherent to therapy due to the enhanced side effects and its impact on the quality of life¹². Another study reported a perceived addiction to opioids as the reason for missing out on pain medications prescribed for cancer treatment¹³.
Shift towards oral medication: As more medicines for cancer therapy are being prescribed to be administered orally, patients are faltering in adherence as medication management becomes patients and families responsibility¹.
Higher comorbidity: Cancer is mostly a disease associated with aging. With older age, people are also likely to suffer from other comorbidities. This results in the complexity of the regimen and lowering of adherence¹⁴.

B. Patients-related factors:

Beliefs: Personal beliefs are rooted in life experiences and current psychological state. Opinions about the importance of medications and their side effects are a salient hindrance to adherence forming the core of “necessity vs. concern belief¹⁵.
Socio-economic factors: Socioeconomic status is not just an important risk factor for cancer but also an important predictor of adherence to therapy.
Support network: Patients with a good support network, either family or friends rate high on adherence¹⁰.

C. Healthcare-related factors:

Personalized care plan: Cancer treatment requires visiting specialist care (oncologists, radiologists, or pathologists) in a specialized health center. Continued care in the same hospital, personalized care plan, and follow-up with medical oncologists were associated with improved adherence¹⁰.
Effective and frequent communication: Communication between the healthcare practitioner and patient is of utmost importance (See our article: Healthcare Providers: a potential springboard for adherence success). Patients giving high value to the doctor’s opinion were more adherent to treatment¹⁰.
Costs: Longer treatment periods for cancer treatment is also a financial burden on patients. Lower out-of-pocket costs are associated with higher adherence¹⁰

Table 1 lists the average rate of medication adherence in major types of cancers and the key barriers to adherence¹⁶.

Type of cancer	Name of the therapy	Adherence Rate	Major barrier	Source
Breast cancer	Hormone therapy (Tamoxifen)	31-73%	Adverse effects, Mental health	Brett et al., 2016¹²
Acute Lymphoblastic Leukemia (ALL)	6-mercaptopurine Methotrexate	85% 81%	Adolescent age, Racial minorities, poor insurance	Yelena et al., 2018¹⁷
Chronic myeloid leukemia	Tyrosine kinase inhibitors	50%	Forgetfulness Longer treatment duration	Rychter et al., 2017¹⁸
Non-hodgkin lymphoma	Oral targeted therapy (ibrutinib)	76 – 96%	Adverse effects Comorbidities	Williams et al., 2019¹⁹
Colorectal cancer	Capecitabine	88.3% – 94%	Metastatic disease, Dyspnea	Figueiredo Junior et al., 2014²⁰
Bladder cancer	Intravesical instillation therapy (BCG)	55%	Adverse effects	Tapiero et al., 2018²¹
Kidney cancer	Sorafenib Sunitinib	90.7 % – 84.8%	Side effects Racial minorities	Murphy et al., 2021²²
Lung cancer	Erlotinib	50 – 80 %	Family structure Treatment concerns Information access	Zhou et al., 2022²³
Prostrate cancer	Apalutamide, Enzalutamide or Abiraterone acetate	42.8 – 53.9 %	Older age, Racial minority Costs	Pilon et al., 2022²⁴
Multiple myeloma	Immunomodulatory drugs	70 %	Cost, Adverse effects, Long-term intake	Cransac et al., 2019²⁵

Demography vulnerable to non-adherence in cancer therapy:

A. Women:

Women are less adherent to medication as compared to men for the same disease²⁶. The adherence rates for breast cancer are higher in well-informed women and lower in patients with negative beliefs about the risk-benefit ratio. Non-adherence is associated with young, very old, and non-white women^12,16.

B. Teenage-young adults:

About 38-50% of adolescents are non-adherent to their oral cancer therapy²⁷, the lowest among all pediatric cancers²⁸. Major challenges are lower self-esteem, peer pressure, mental health, and perceived beliefs about illness severity, treatment efficacy, and parent-child discordance²⁷.

C. Older adults:

Non-adherence to medication is higher in older patients due to cognitive & sensory impairment. Older patients are also more likely to be suffering from other comorbidities leading to non-adherence¹⁴.

Overcoming barriers to adherence in cancer therapy:

Patient-provider interaction: Interventions that increase the quality and frequency of patient-provider communication and patients’ overall satisfaction with the healthcare visit are crucial for adherence. It lowers concern-beliefs and raises their confidence in the necessity of the treatment²⁹.

Tailored communication: Educational communications tailored to match the patient’s treatment level in written or digital form can enhance adherence. The information could include mechanisms, adverse effects, and the importance of therapy along with remedies to mitigate them. It should also discuss ways to improve lifestyle and should list helpline numbers for further assistance¹⁶. COMPAS trial, reported significantly enhanced adherence in patients receiving such interventions (64.7% v.s.48% in the control group³⁰. Web-based applications that remind about medication, allow reporting adverse events, and receive appropriate care will help³⁰.

Conclusion:

Although cancer cure is largely dependent on timely detection and effective treatment breaking the adherence barriers will be the tipping point toward the success of cancer treatment in real-world practice. The paradigm shift in cancer care towards oral therapies prescribed for longer durations is mirroring the difficulties faced for chronic diseases. This brings the spotlight on medication adherence to achieve the expected treatment benefits from cancer therapy¹¹.

“Cure sometimes, treat often, and comfort always.”
― Hippocrates