Navigating Complexity in the Precision Oncology Clinic: Pharmacists’ Central Role in Drug Selection, Acquisition, and Dosing in a Real-World Clinic

Precision oncology is a transformative approach to cancer care that personalizes treatment based on the unique characteristics of an individual patient and their tumor. Because most advanced malignancies have multiple deleterious genomic alterations that demonstrate interpatient heterogeneity, precision cancer treatment involves customized biomarker-matched combination therapy (rather than matching single drugs to individual pathogenic molecular alterations). Previous studies have indicated that improved survival outcomes correlate with higher degrees of biomarker matching.[1] Implementation of complex precision regimens is contingent on addressing clinical nuances and individual factors that maximize effectiveness and minimize toxicity. Organ function, drug interactions, pharmacogenomics (PGx), and unique patient factors (age, frailty, and more) must all be considered when establishing a treatment plan. Precision medicine means giving not only the right drugs but also the right doses for each patient, rather than a “one-size-fits-all” strategy.[2]

As part of a multidisciplinary care team, clinical precision medicine oncology pharmacists are well suited and crucial to addressing factors that relate to drug-drug interactions and personalized dosing. Using evidence-informed dosing, guidelines for organ dysfunction, drug interaction screening and mitigation, and Clinical Pharmacogenetics Implementation Consortium (CPIC)/Dutch Pharmacogenetics Working Group (DPWG) PGx guidelines (including pharmacogenomic testing), pharmacists can help prevent avoidable toxicity and suboptimal treatment. Hematology Oncology Pharmacists Association (HOPA) positions oncology pharmacists as essential for dosing and scheduling, toxicity prevention, patient education, drug acquisition, and longitudinal medication management. In this article, we address practical interventions across these complexities and, based on our experience in our precision oncology clinic, highlight the critical role of the pharmacist in operationalizing and optimizing precision medicine treatment strategies (Table 1).

Table 1.

Role of pharmacist in the precision oncology clinic

Role	Examples
Organ function review	Kidney, liver, cardiac, blood counts
Drug interactions	Food, noncancer medications, supplements, other cancer medications
Pharmacogenomics	DPYD, UGT1A1, CYP enzymes
Patient factors	Age, weight, ethnicity, frailty, ECOG Performance Status, home support
Patient education	Dosing; interaction with other medications, food, and supplements; side effects and prophylactic recommendations; safe handling; refills
Medication acquisition	Navigating payors, including appeals and denials; physician-pharmacist discussion regarding equivalent medication substitution; pharmaceutical industry patient assistance programs; specialized pharmacies offering discounts

ECOG: Eastern Cooperative Oncology Group.

Dosing systemic anticancer therapies requires careful consideration of disease-related impacts and an individual’s ability to metabolize and eliminate a drug from their system. For drugs cleared by the kidneys, estimating renal function is essential for determining a target range and a monitoring plan even when renal adjustments are not specified in a drug’s package insert. Serum creatinine provides a surrogate measurement for renal filtration. In cancer, serum creatinine can occasionally overestimate true kidney function and inflate creatinine-based estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl), risking higher-than-intended drug exposure. Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline recommends using creatinine-based eGFR as a starting point and, when available, confirming with cystatin C or the combined creatinine-cystatin C equation (eGFRcr-cys) to improve accuracy in abnormal muscle-mass states—an important factor to consider in oncology due to the phenomenon of cancer cachexia. Pharmacists play a critical role in documenting which estimate was selected, the rationale for its selection, and how it informed the initial dosing decision. Then, pharmacists can recommend dose adjustments moving forward based on objective laboratory values while remaining adherent with Food and Drug Administration (FDA) guidelines that specify dose recommendations based on renal function from individual drug package inserts.

Many oncology drugs also pose a dosing challenge when it comes to hepatic dysfunction, and pharmacists play a critical role in interpreting limited guidance from package inserts and published data. FDA hepatic impairment guidance explains why many package inserts omit a fixed starting dose recommendation at launch; pharmacokinetics data stratified by bilirubin, albumin, and international normalized ratio (INR) may be incomplete.[3] Pharmacists can help critically evaluate the pharmacokinetics mechanism of drugs and extrapolate dose adjustments. Before starting therapy, it is important to assess a full liver panel. These markers can help to identify causes of hepatic injury (tumor infiltration, blocked bile ducts, sepsis, other hepatotoxins, etc.) and guide whether to continue, hold, or adjust therapy while evaluating the cause. As an example, abemaciclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor extensively metabolized in the liver, typically requires no adjustment in Child-Pugh A or B but is reduced to once-daily dosing in Child-Pugh C, with liver function monitoring to detect hepatotoxicity.[4] Everolimus, a mammalian target of rapamycin (mTOR) inhibitor with exposure that increases as hepatic function worsens, is started at reduced doses by Child-Pugh class and then adjusted based on tolerability.[5] In both cases, pharmacology and expected exposure changes guide the initial dose and monitoring plan. Pharmacists can assist in analyzing whether changes are caused by the drug therapy or from disease progression, bile-duct blockage, or co-medication hepatoxicity.

In oncology, patients are frequently prescribed complex regimens that include supportive therapies, over-the-counter (OTC) medications, and holistic remedies or supplements—which can be suggested by both healthcare professionals and nonprofessionals—creating a substantial risk for clinically significant drug-drug interactions. Pharmacists perform thorough medication reconciliations and identify mechanisms that may introduce clinical risk. As an example, for absorption-related drug interactions, many oral tyrosine kinase inhibitors (TKIs) require an acidic environment to dissolve. Acid-suppressing agents can reduce exposure and efficacy. Management includes avoiding combinations, separating dosing times, and counseling on food effects for food-sensitive TKIs.[6]

For metabolic drug-drug interactions, many oncolytics are CYP3A4 substrates, so strong inhibitors may require dose reductions or switching to another agent to avoid toxicity. Meanwhile, strong inducers can lower exposure and compromise efficacy. Some anticancer agents themselves inhibit or induce CYP3A4, requiring close monitoring, dose adjustments, or substitutions based on a patient’s concomitant medications.[6] There are a variety of other CYP enzymes involved in oncolytic breakdown, and pharmacists should always assess interactions before starting therapy.

PGx is an important, yet underutilized, tool in oncology. PGx can help personalize therapies based on patient-specific genomics, which can avoid toxicity while preserving efficacy. Pharmacists can help to apply PGx to real-world patient care by translating results into clear recommendations for prescribing, dosing, and monitoring. For example, patients with DPYD loss-of-function variants have an increased risk of severe, early toxicity from 5-fluorouracil (5-FU) or capecitabine.[7] FDA package inserts for 5-FU and capecitabine have been recently updated to include a boxed warning highlighting the risk of serious adverse reactions and advises testing before treatment initiation, unless immediate treatment is necessary, and avoiding use in patients with certain loss-of-function homozygous or compound heterozygous DPYD variants that result in complete dihydropyrimidine dehydrogenase (DPD) deficiency.[8,9] This is a workflow pharmacists can lead through education, ordering testing, and implementation of reflexive testing protocols within their institutions to ensure all patients are tested before treatment initiation.

Another example pertains to irinotecan, which is a topoisomerase I inhibitor used mainly for advanced colorectal and pancreatic cancer; it commonly causes neutropenia and diarrhea. It is metabolized to SN-38, which is detoxified by UGT1A1 enzymes. Reduced UGT1A1 activity, especially the UGT1A1 *28/*28 genotype, increases toxicity risk. About 10% of North Americans are homozygous. Guidelines recommend lowering starting doses for homozygous patients, whereas heterozygotes usually require no dose adjustment. The FDA and European groups provide genotype-based dosing guidance for safer irinotecan use.[10]

Some oncolytic drugs include pharmacogenomic guidance. Erdafitinib is mainly metabolized by CYP2C9 and CYP3A4, and the FDA label notes that patients with CYP2C9 *3/*3 may have approximately 50% higher exposure, warranting closer monitoring for toxicity.[11] In practice, pharmacists flag known poor metabolizers, intensify early monitoring, and prepare for dose holds or adjustments if adverse effects occur. If genotype is unknown, monitoring is recommended when CYP2C9/3A inhibitors or inducers are used. Overall, more robust FDA and manufacturer guidance on pharmacogenomic dosing of oncolytics is still needed.

Phenoconversion in PGx occurs when a patient’s actual drug metabolism differs from what their genotype would predict, often due to external influences such as co-administered medications, organ dysfunction, or disease-related factors (such as cancer) that alter enzyme activity.[12] This phenomenon is prevalent yet not widely integrated into clinical practice. For example, tamoxifen for estrogen receptor–positive breast cancer requires CYP2D6 to form its active metabolite, endoxifen. If a genetically normal CYP2D6 metabolizer takes the antidepressant paroxetine, a strong CYP2D6 inhibitor, phenoconversion can occur, functionally shifting the patient to a poor metabolizer. This may lower endoxifen levels and reduce tamoxifen effectiveness, so the patient is classified as a CYP2D6 poor metabolizer as per the University of Florida algorithm.[13] For CYP2D6 poor metabolizers, CPIC recommends considering alternative endocrine therapies.[14] Although these phenoconversion models provide a general and quantitative approach to assessing drug metabolism phenotypes in patients, individual risk factors may significantly impact metabolism and should be considered when determining personalized drug dosing. Clinical precision medicine oncology pharmacists play a critical role in evaluating these factors to optimize and individualize medication therapy.

In addition to nationally recognized CPIC guidelines, multidisciplinary teams also utilize FDA PGx resources. The FDA’s Table of Pharmacogenomic Biomarkers in Drug Labeling identifies gene-drug relationships already in drug labels, whereas the Table of Pharmacogenetic Associations summarizes evidence that may not yet be on the label.[15,16] In practice, pharmacists pair PGx with drug-drug interaction checks and organ function assessments so that genotype-guided decisions are not compromised by modifiable factors.

Beyond labs and genomics, oncology success depends on matching treatment intensity to a patient’s physiologic resilience. The Eastern Cooperative Oncology Group (ECOG) Performance Status is a practical measure of functional capacity and predicts toxicity, treatment feasibility, and supportive care needs. Multidisciplinary teams use ECOG scores to guide risk-benefit decisions, adjust schedules, or de-escalate therapy to achieve treatment goals while minimizing avoidable harm. Because age alone poorly predicts tolerance, structured geriatric assessment better guides care for adults ≥65 years old. The American Society of Clinical Oncology (ASCO) recommends it to identify risks (falls, cognition, mood, nutrition, comorbidities, polypharmacy, and social support) that affect adherence and toxicity.[17] Pharmacists can act on results by tailoring antiemetics, using early growth-factor support, simplifying regimens and delivery, and arranging closer follow-up for patients with limited support. These clinical judgments account for preexisting comorbidities and potential adverse effects, including medication-induced hyperglycemia in diabetes, reduced ejection fraction with anthracyclines or mitogen-activated protein kinase kinase (MEK) inhibitors in cardiovascular disease, and infection risk with myelosuppressive therapies. Pharmacist involvement helps ensure the plan is feasible and safe for each patient.

Many patients with cancer, especially older adults, take multiple medications (“polypharmacy”). Before adding new drugs, pharmacists play a key role in educating patients about dosing, food requirements, potential toxicities, and drug interactions. They help patients understand how to take medications correctly, manage side effects, alert patients to which side effects should be reported early, and help patients adhere to complex and often costly treatment regimens, including by aligning dosing schedules with patient routines. Pharmacists can also coordinate refills and education to reduce overwhelming patients and maintain adherence.

In precision oncology, medication acquisition may be a key barrier to treatment and must be properly operationalized. Biomarker-based combination therapy may require navigation to secondary clinical trials, which can be enabled by a clinical trial navigator, or the use of off-label or combinations of on-label and off-label drugs. For patients with cancer, medications must be accessed quickly, as those with advanced malignancies often cannot wait many weeks for treatment. Pharmacists can play a fundamental role in drug acquisition based on their knowledge about individual insurance coverage, navigating denials and writing appeals, substitution of more easily acquired equivalent anticancer drugs with the same or similar targets, complex pharmaceutical industry patient assistance programs that provide free drug under specific circumstances that differ from company to company, and specialized pharmacies that sell select drugs at significantly reduced prices. Experience in our precision oncology clinic and cancer center suggests that pharmacist-physician discussion during treatment decision-making can prevent wasted time and effort in navigating the system and facilitates a treatment plan with high likelihood of timely drug acquisition.

Precision oncology personalizes cancer treatment by matching therapies to each patient’s tumor biology. Evidence shows improved survival with higher degrees of biomarker matching. Maximizing safety and quality of life requires individualized dosing considerations that account for organ function, drug-drug interactions, PGx, and patient-specific factors such as age, frailty, and comorbidities. Clinical precision medicine oncology pharmacists are essential contributors to multidisciplinary precision oncology teams, leveraging expertise in dosing optimization, toxicity mitigation, pharmacogenomic interpretation, patient education, and medication access to operationalize personalized cancer care.