Practical Guidance for the Management of Adverse Events in Patients with KRASG12C-Mutated Non-Small Cell Lung Cancer Receiving Adagrasib.

Adagrasib (MRTX849) is a KRASG12C inhibitor with favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system (CNS) penetration. As of September 1, 2022, a total of 853 patients with KRASG12C-mutated solid tumors, including patients with CNS metastases, had received adagrasib (monotherapy or in combination). Adagrasib-related treatment-related adverse events (TRAEs) are generally mild to moderate in severity, start early in treatment, resolve quickly with appropriate intervention, and result in a low rate of treatment discontinuation. Common TRAEs seen in clinical trials included gastrointestinal-related toxicities (diarrhea, nausea, and vomiting); hepatic toxicities (increased alanine aminotransferase/aspartate aminotransferase) and fatigue, which can be managed through dose modifications, dietary modifications, concomitant medications (such as anti-diarrheals and anti-emetics/anti-nauseants) and the monitoring of liver enzymes and electrolytes. To manage common TRAEs effectively, it is imperative that clinicians are informed, and patients are fully counseled on management recommendations at treatment initiation. In this review, we provide practical guidance on the management of adagrasib TRAEs and discuss some best practices for patient and caregiver counseling to facilitate optimal outcomes for patients. Safety and tolerability data from the phase II cohort of the KRYSTAL-1 study will be reviewed and presented with practical management recommendations based on our experience as clinical investigators.

International Society of Oncology Pharmacy Practitioners (ISOPP) position statement: Role of the oncology pharmacy team in cancer care.

The Oncology Pharmacy Team (OPT), consisting of specialty-trained pharmacists and/or pharmacy technicians, is an integral component of the multidisciplinary healthcare team (MHT) involved with all aspects of cancer patient care. The OPT fosters quality patient care, safety, and local regulatory compliance. The International Society of Oncology Pharmacy Practitioners (ISOPP) developed this position statement to provide guidance on five key areas: 1) oncology pharmacy practice as a pharmacy specialty; 2) contributions to patient care; 3) oncology pharmacy practice management; 4) education and training; and 5) contributions to oncology research and quality initiatives to involve the OPT. This position statement advocates that: 1) the OPT be fully incorporated into the MHT to optimize patient care; 2) educational and healthcare institutions develop programs to continually educate OPT members; and 3) regulatory authorities develop certification programs to recognize the unique contributions of the OPT in cancer patient care.

Healthcare services expenditures among prostate cancer patients with and without mood disorders in the United States: A propensity score-matched cross-sectional study.

OBJECTIVES: To compare the averages of healthcare services utilization and of expenditures for men with prostate cancer with and without diagnoses of mood disorders applying propensity score matching (PSM), and to identify the potential predictors associated with increased healthcare expenditures. DESIGN: Cross-sectional study. SAMPLE AND METHODS: A total of 308,602 weighted patients with prostate cancer were identified after applying PSM. The datasets for men with prostate cancer were extracted from the Medical Expenditure Panel Survey (MEPS) from 2010 to 2015. For cohort formation, 1:1 PSM was applied. Healthcare utilization and expenditures analyzed included emergency room visits, length of stay for hospital inpatients, outpatient visits, office-based visits, and prescriptions. Generalized linear model with gamma distribution and log link was used to determine which covariates are associated with the increase in healthcare expenditures for each healthcare service. FINDINGS: The mean expenditures for emergency room visits between men with prostate cancer and mood disorders was $3,092.34, and it was $1,330.64 for patients without mood disorders (p = 0.038). The weighted total expenditures for emergency room visits in prostate cancer patients with mood disorders is 57% higher (p = 0.0109). Moreover, the weighted total expenditures for outpatient visits in prostate cancer patients with mood disorders is 93% higher (p = 0.0001). The potential predictor in total healthcare expenditures is perceived health status (fair/poor) (p = 0.0066). CONCLUSIONS AND IMPLICATIONS FOR PSYCHOSOCIAL PROVIDERS OR POLICY: Individuals with a diagnosis of mood disorders were found to have higher average healthcare expenditures in emergency room visits than those without mood disorders. Therefore, the implications of this study are to inform the patient care team that the assessment and management of mood disorders is a priority. Moreover, screening of mood- disorder symptoms should occur early to optimize care. Finally, policymakers should provide accessible care to minimize emergency room visits.

Women in oncology pharmacy leadership: A white paper.

Gender disparity exists in leadership roles within healthcare. While the majority of the healthcare workforce is comprised of women, significantly fewer women occupy leadership positions, particularly at executive and board levels. As the field of oncology pharmacy continues to rapidly expand and evolve, an assessment of the current state of women in oncology pharmacy leadership roles is vital to the growth and development of the profession. In the fall of 2017, the Hematology/Oncology Pharmacy Association (HOPA) hosted a summit to explore leadership issues facing women in oncology pharmacy which have the potential to affect our membership and our profession. This meeting included invited participants from across the fields of oncology and pharmacy and was part of HOPA's strategic leadership initiative developed through the work of the HOPA Leadership Development Committee in 2016. This promotes a primary goal of HOPA, which is to support oncology pharmacists as they assume leadership roles within their practices and within healthcare to assure oncology pharmacy is integrated into cancer care. The purpose of this white paper is to (1) summarize key issues that were identified through a membership survey; (2) review ongoing efforts to address the needs of female oncology pharmacists in leadership development; (3) serve as a call to action for individuals and professional organizations to assist with and disseminate these efforts and highlight available resources, and (4) to provide practical steps to meet the needs of individuals, training programs, and institutions/employers.

Assessment of community pharmacists' confidence, foundational knowledge, and coordination of care activities in patients with cancer as a chronic condition.

OBJECTIVES: To develop and deliver a series of structured educational programs to community pharmacists to build on current foundational knowledge of cancer and cancer therapy. The specific objectives were to: 1) develop and provide an educational program focused on oncology pharmacy practice in the community; and 2) measure the program impact on participants' confidence, foundational knowledge, and coordination of cancer care activities. PRACTICE INNOVATION: A structured, in-person, 6-hour educational program tailored for community pharmacists was developed and delivered along with two 20-minute online webinar sessions. The topics identified for the webinars were based on solicited feedback from participants attending the live educational program. EVALUATION: A pre- and post-survey was used to evaluate the participant's assessment of the live educational program, and a retrospective survey was used to evaluate the education sessions. RESULTS: Twenty-one pharmacists attended the in-person session. Participants indicated that they were more confident and able to coordinate care after the educational intervention. There was a nonsignificant improvement in foundational knowledge. CONCLUSION: The educational sessions provided current relevant information for community pharmacists to build on knowledge of oncology pharmacy practice and resources. This increased the pharmacists' confidence to address needs and facilitate coordination of care for individuals with cancer. Delivery of education tailored to community pharmacy is important as the advancing cancer care model continues to adapt with new medications and innovations.

Clinical pharmacology of oncology agents in older adults: A comprehensive review of how chronologic and functional age can influence treatment-related effects.

Unique challenges exist when managing older adults with cancer. Associations between cancer and age-related physiologic changes have a direct impact on pharmacokinetics and pharmacodynamics of cancer therapies and can affect drug dosing, dose intensity, efficacy, safety and quality of life. The breadth and depth of these issues, however, have not been fully evaluated because the majority of clinical trials have focused on a younger and healthier population. As a consequence, little information is available to support clinicians in making evidence-based decisions regarding treatment with cancer therapies in older adults, especially those over age 75. Prior clinical pharmacology reviews summarized the literature on how age-related physiologic changes can influence and affect conventional and targeted anti-cancer treatments. Our article provides an updated review with expanded information that includes small molecule kinase inhibitors, monoclonal antibodies, immunotherapies, hormonal, conventional, and miscellaneous agents. Additionally, our article integrates how functional age, determined by the geriatric assessment (GA), can also influence treatment-related effects and health outcomes. Broadening cancer therapy trials to capture not only chronologic age but also functional age would allow clinicians to better identify subsets of older adults who benefit from treatment versus those most vulnerable to morbidity and/or mortality.

Older Adults With Lung Cancer: Assessment, Treatment Options, Survivorship Issues, and Palliative Care Strategies.

BACKGROUND: Treatment advances offer options for cancer treatment in older adults that are less invasive and have fewer side effects. Geriatric assessment is a key component of treatment planning to identify functional and physiologic status and is the basis of decision making. OBJECTIVES: This article discusses the role of geriatric assessment, treatment options (e.g., surgical, chemotherapy, radiation therapy), survivorship issues, and palliative care strategies for older adults with cancer. METHODS: Literature was reviewed to identify geriatric assessment implications, current treatment strategies, and survivorship and palliative care interventions for older adults with cancer based on a case study approach. FINDINGS: Geriatric assessment is key to identifying deficits and disabilities in older adults with cancer and is a critical component in oncology treatment planning. Evidence-based, less invasive treatment options are available and offer older adults more tolerable oncologic therapies.

Management of Venous Thromboembolism for Patients With Hematologic Malignancies.

Advanced practitioners are an integral part of the cancer care team. Therefore, it is imperative they are knowledgeable of risk factors associated with venous thromboembolism in the oncology setting, including signs or symptoms and management.

Multiple myeloma maintenance therapy: a review of the pharmacologic treatment.

Over the last decade, numerous drug therapies have emerged for the treatment of multiple myeloma including immunomodulating agents namely thalidomide, lenalidomide, and pomalidomide and proteasome inhibitors namely bortezomib and carfilzomib. These agents have transformed the treatment of multiple myeloma and the role of high-dose chemotherapy followed by stem cell transplantation in the treatment of the disease. There are now studies that evaluate the use of drug therapy as maintenance following autologous stem cell transplantation; these studies have shown improvements in surrogate endpoints such as progression-free survival. Studies that have evaluated thalidomide or lenalidomide maintenance therapy have demonstrated an overall survival (OS) benefit in individuals with multiple myeloma who received high-dose chemotherapy followed by stem cell transplantation. A meta-analysis of thalidomide maintenance therapy did show a possible late survival benefit. The use of dexamethasone, thalidomide, lenalidomide, or combination bortezomib with thalidomide in patients who did not undergo transplantation demonstrated progression-free survival benefit; although there was no OS advantage for these agents in this population. There are a number of important considerations when selecting a drug therapy strategy for maintenance therapy which includes practical considerations such as route of administration and frequency of administration. Additionally, patient-specific elements such as potential toxicities, end-organ function, quality of life, cytogenetics, and previous treatment should be considered. Additional studies are needed to elicit the timing for initiation and duration of maintenance therapy, determine the role of cytogenetics, further characterize possible resistance patterns, and determine the combinations necessary to achieve an optimal increase in OS. Until more data are available, the risks and benefits should be evaluated on a patient-specific basis when deciding to initiate maintenance therapy or observation.

Navigating the seasons of survivorship in community oncology.

Nurses have an important role in the development, implementation, and evaluation of cancer survivorship programs. Growing numbers of cancer survivors challenge community oncology practices to incorporate survivorship care according to new standards and guidelines. In response, one community-based oncology clinic created an advanced practice nurse (APN)-led survivorship program using the concept of Seasons of Survival as a guide. Survivorship care, when based on a more expansive definition of survivorship as beginning at the time of diagnosis, encompasses holistic nursing and multidisciplinary care. The APN assesses each patient's concerns and quality of life using a validated measure to tailor survivorship and supportive care. This article reviews the foundation and structure of the program in detail, describes program implementation using case studies, and outlines the program evaluation process and results.

Cancer- and chemotherapy-induced anemia.

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.

Antiemetics: American Society of Clinical Oncology clinical practice guideline update.

PURPOSE: To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. METHODS: A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. RESULTS: Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists. RECOMMENDATIONS: Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.

Safe handling of oral chemotherapeutic agents in clinical practice: recommendations from an international pharmacy panel.

Although there has been a significant increase in the availability and use of oral chemotherapeutic agents, the guidelines around their safe handling are still evolving. Although oral chemotherapy is associated with ease of administration, it has the same exposure risks to health care practitioners, patients, and their caregivers as intravenous formulations, and because it is administered in the home, to the families of patients. However, the general misconception appears to be that exposure risk is low and therefore oral chemotherapeutic agents present little risk and are safer to handle. In a series of three roundtable meetings, a team of international pharmacists from North America and Europe reviewed existing guidelines and identified gaps in recommendations that we believe are important for safe handling. The present article is a compilation of these gaps, especially applicable to manufacturers and distributors, storage and handling, and patient education regarding safe handling. These recommendations, on the basis of our experience and of best practices, provide an international perspective and can be adapted by institutions and practices for development of standardized procedures specific to their needs for the safe handling of oral chemotherapeutic agents.

NCCN Task Force Report: Specialty Pharmacy.

The use of specialty pharmacies is expanding in oncology pharmacy practice. Specialty pharmacies provide a channel for distributing drugs that, from the payor perspective, creates economies of scale and streamlines the delivery of expensive drugs. Proposed goals of specialty pharmacy include optimization of pharmaceutical care outcomes through ensuring appropriate medication use and maximizing adherence, and optimization of economic outcomes through avoiding unwarranted drug expenditure. In oncology practice, specialty pharmacies have become a distribution channel for various agents. The use of a specialty pharmacy, and the addition of the pharmacist from the specialty pharmacy to the health care team, may not only provide benefits for care but also present challenges in oncology practice. The NCCN Specialty Pharmacy Task Force met to identify and examine the impact of specialty pharmacy practice on the care of people with cancer, and to provide recommendations regarding issues discussed. This report provides recommendations within the following categories: education and training of specialty pharmacy practitioners who care for individuals with cancer, coordination of care, and patient safety. Areas for further evaluation are also identified.

Current and emerging treatments for multiple myeloma.

BACKGROUND: The prognosis and treatment of multiple myeloma (MM) has evolved greatly over the past decade. The development and incorporation of new agents such as immunomodulators and proteasome inhibitors into therapy has improved outcomes and is helping patients enjoy longer periods of remission. OBJECTIVE: To review current treatments for MM, including overview of drug therapy and management of adverse effects of therapy and comorbidities. Additionally, an overview of agents being studied and evaluated for use in MM and myeloma-related conditions, such as metastatic bone disease and venous thromboembolism, will be discussed. SUMMARY: Great strides have been made regarding the understanding of disease pathology in MM, leading to therapies that may be targeted to each individual, based on their unique biology of disease. Therapy is currently tailored based on patient issues and stage of disease, but may soon be tailored individually based on the cytogenetic profile of a patient. Recent treatment guidelines have been published by the National Comprehensive Cancer Network which were updated with impressive results from clinical trials involving agents such as immunomodulators and proteasome inhibitors. This guideline also provides information on the management of myeloma and treatment-related morbidities. As with the treatment of any cancer, clinicians must weigh risk versus benefit when determining the most appropriate therapy. Currently, corticosteroids, lenalidomide, thalidomide, and bortezomib are all used in patients with MM. The use of chemotherapy, including high-dose therapy with stem cell transplant, is an important component of treatment for many patients. The use of high-dose therapy is continually being evaluated, and the issue of risk versus benefit is weighed for individual patients. Depending on the prognosis, it may be of benefit to endure the toxicity of higher doses to achieve a better overall response and achieve longer remission periods. Although stem cell transplantation is often performed in MM to improve survival and remission rates, some patients are unable to undergo transplant for a variety of reasons, including age (older than 65 years), comorbidities, and/or organ dysfunction. Newer drug therapies and combinations of therapy are being evaluated to better manage this population and patients who previously received high-dose chemotherapy and a stem-cell transplant. Additionally, the management of relapsed, or refractory, disease continues to be a challenge in treating the myeloma patient. Despite aggressive and improved treatments, most myeloma patients will eventually have resistance to therapy or relapse. Treatment strategies in these patients are also evolving. CONCLUSION: Major advancements in the diagnosis, staging, and treatment of myeloma offer promise in the future for changing MM from a terminal illness into a chronic, manageable condition.

Management of early and advanced colorectal cancer: therapeutic issues.

PURPOSE: The staging of colorectal cancer, therapeutic decision making in the management of early and advanced colorectal cancer, and dilemmas posed by drug-related toxicity are discussed. SUMMARY: Staging of colorectal cancer occurs after surgery and is based on the extent of disease invasiveness and dissemination. Surgery is the primary treatment for stage I disease. Adjuvant chemotherapy is recommended after resection in selected high-risk patients with stage II disease and in all patients with stage III disease. Convenience of administration, tolerability, and patient factors not necessarily age may be considerations in decisions about adjuvant therapy after resection. Treatment of stage IV colorectal cancer is based on the type of prior therapy and patient-specific factors. Recently, significant improvements in survival have been achieved through the use of combination chemotherapy and monoclonal antibody regimens. Bevacizumab in combination with chemotherapy is first-line therapy for stage IV disease. Age alone should not preclude the use of chemotherapy in stage IV colorectal cancer, although the ability to tolerate drug-related toxicity may be a consideration. The optimal duration of chemotherapy in patients with early and metastatic colorectal cancer is unclear. CONCLUSION: The optimal approach to the treatment of colorectal cancer depends on several considerations, including patient-specific factors.

Anemia in patients with cancer: incidence, causes, impact, management, and use of treatment guidelines and protocols.

PURPOSE: The incidence, etiology, impact, and considerations in developing guidelines for treating anemia in patients with cancer are described. SUMMARY: Anemia is common in patients with cancer. The incidence and severity of anemia depend on the type and extent of the malignancy; the type, schedule, and intensity of cancer therapy; and patient age, gender, and comorbid conditions. Anemia may be the result of the malignancy itself, cancer treatment, blood losses, nutritional deficiencies, hemolysis, endocrine disorders, or inflammatory cytokines associated with chronic disease. Anemia can have a profound impact on physical and psychosocial function and quality of life. Guidelines and protocols for treating anemia should be evidence-based and take into consideration patient age, the type and extent of malignancy, comorbid conditions, and the etiology and impact of anemia. Patient-specific issues that guidelines should address include strategies for identifying patients with anemia, treating anemia, evaluating the response to treatment, and modifying treatment based on response. Erythropoietic agents are preferred over blood transfusions for patients whose anemia is chronic, although transfusions are indicated for acute, severe blood losses. Iron supplementation often is required in patients receiving erythropoietic therapy or with iron deficiency due to hemorrhage. CONCLUSION: The use of evidence-based guidelines and protocols that take into consideration the heterogeneity of patients with cancer can optimize anemia treatment.