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The treatment landscape of hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer has been modernized by the identification of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. Because the majority of HR+ breast cancers will develop resistance to endocrine therapies (tamoxifen and aromatase inhibitors), newer treatment options are necessary to restore endocrine sensitivity and prolong survival. Ribociclib and abemaciclib are two of three CDK4/6 inhibitors currently approved for first- and second-line treatment of HR+/HER2– metastatic breast cancer. Data from large, phase III clinical trials have demonstrated an improvement in both progression-free and overall survival with the addition of ribociclib or abemaciclib to endocrine-based therapy, establishing a new frontline standard of care. Treatment with ribociclib and abemaciclib provide a convenient oral treatment option that is both efficacious and well tolerated.

Sacituzumab govitecan was initially approved in April 2020 under accelerated approval for the treatment of patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. A confirmatory phase III trial evaluating sacituzumab govitecan vs. chemotherapy of the provider’s choice was published in April 2021. Based on this trial, the FDA granted sacituzumab govitecan full regulatory approval. This antibody-drug conjugate is composed of a monoclonal antibody targeted at Trop-2 and contains the active metabolite of irinotecan, SN-38, as a cytotoxic side moiety. In a phase III clinical trial, sacituzumab govitecan demonstrated a median progression-free survival of 5.7 months vs. 1.7 months with chemotherapy. It is now an additional option for patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease.

Cytomegalovirus (CMV) is a double-stranded DNA virus that infects (seropositive on screening) more than half of adults by age 40. However, reactivation of detectable viral load (CMV reactivation) typically occurs only in immunocompromised patients. Notably, CMV reactivation after allogeneic hematopoietic cell transplant (HCT) can increase treatment-related mortality almost 2-fold compared to patients who do not have reactivation. Historically, prevention of CMV reactivation mainly included the preemptive strategy of serial monitoring of viral load and initiating an antiviral once the viral load became elevated in an effort to prevent end-organ disease. The major limitations of the antiviral agents utilized in preemptive therapy are myelosuppression and renal toxicity. In 2017, a first-in-class viral terminase complex subunit inhibitor, letermovir, became the only U.S. Food & Drug Administration-approved medication to prevent CMV reactivation after allogeneic HCT (e.g., as prophylaxis). In a phase III trial, patients who were randomized to letermovir prophylactically had decreased rates of CMV viremia leading to preemptive therapy. The purpose of this article is to describe the need for safe and effective medication to prevent CMV reactivation, the clinical efficacy of letermovir, and the impact oncology advanced practitioners can play in reducing CMV reactivation in patients undergoing allogeneic HCT.

In 1991, the U.S. Food & Drug Administration (FDA) approved rmetHuG-CSF for human use. This recombinant methionyl human granulocyte colony-stimulating factor, or filgrastim, saw use in over 1 million patients in its first 5 years on the market. In 2002, the FDA approved a version of filgrastim with covalent linkage to a monomethoxypolyethylene glycol, increasing the molecular size and half-life to replace multiple days of dosing with a single injection. These medications remained standard of care for neutropenia until the Biologics Price Competition and Innovation Act of 2009 created an abbreviated pathway to licensure for biologic products. Practitioners now have their pick of numerous and expanding options for pegfilgrastim biosimilars.

The B-cell receptor signaling pathway plays an integral role in the proliferation and survival of malignant B cells. Targeting the B-cell receptor pathway via the inhibition of Bruton tyrosine kinase (BTK) has evolved the treatment of a variety of B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, marginal zone lymphoma, and Waldenström macroglobulinemia. Currently, there are three BTK inhibitors approved by the U.S. Food and Drug Administration: ibrutinib, acalabrutinib, and zanubrutinib. This article reviews the pharmacology, clinical efficacy, safety, dosing, drug-drug interactions, and implications for advanced practitioners of BTK inhibitors in the treatment of B-cell malignancies.

Acute thrombotic thrombocytopenic purpura (aTTP) is a rare microangiopathic hemolytic anemia. Standard of care currently includes plasma exchange and immunosuppressive agents, including glucocorticoids, vincristine, and rituximab. Even with these therapies, relapse occurs in 36% of patients, and mortality ranges from 10% to 20%. Caplacizumab is a novel agent approved for the treatment of adult patients with aTTP in conjunction with plasma exchange and immunosuppressive therapies. It works by binding to the A1 domain of von Willebrand factor (VWF), blocking platelets from binding to VWF and aggregating. In clinical trials, patients who received caplacizumab compared with placebo were more likely to have a normalization of their platelet count, a lower rate of recurrence, and a lower incidence of the composite of aTTP-related death, recurrence, or major thromboembolic event. The side effect profile is rather benign and includes epistaxis, headache, and gingival bleeding. Caplacizumab is only available through specialty pharmacy services due to its high cost. Providers should be aware of and prepared for the prior authorization process required to assist their patients in gaining access to the medication. Currently, there is no formal consensus regarding caplacizumab’s place in therapy for patients with aTTP, but it remains an option for refractory cases.

The treatment paradigm for urothelial carcinoma (UC), a common genitourinary cancer, has significantly expanded in recent years. Enfortumab vedotin, a Nectin-4–targeted antibody-drug conjugate, was recently approved by the U.S. Food & Drug Administration for patients with advanced or metastatic UC following chemotherapy and immunotherapy. Approval of enfortumab vedotin was based on findings from the EV-201 trial, which demonstrated objective response rates of 44%. Patients treated with enfortumab vedotin should be monitored for specific toxicities, including peripheral neuropathy, rash, and hyperglycemia. In this article, the clinical implications of enfortumab vedotin for the treatment of advanced UC are reviewed.

Acute myeloid leukemia (AML) is the most common adult leukemia, with an overall poor prognosis. New agents targeting various receptors may improve treatment outcomes and overall survival. FMS-like tyrosine kinase 3 (FLT3) is a targetable mutation occurring in one third of AML patients. It contributes to increased tumor proliferation and decreased cellular differentiation, ultimately conferring a poor overall prognosis. Among patients with FLT3-positive relapsed/refractory AML, outcomes are particularly dismal. Gilteritinib is a novel, second-generation FLT3 inhibitor approved by the U.S. Food & Drug Administration (FDA) for the treatment of relapsed/refractory AML with an FLT3 mutation as detected by an FDA-approved test.

Prostate cancer is the fourth leading cause of cancer in the United States. Treatment of this oncologic disease involves a variety of different modalities including surgery, radiation, and systemic therapy. Systemic therapy is used for locally advanced and metastatic disease, and primarily involves hormonal blockade as a mechanism of disease control. Apalutamide is a nonsteroidal androgen receptor inhibitor that binds directly to the androgen receptor ligand binding-domain to prevent androgen receptor translocation. This agent is used in combination with gonadotropin-releasing hormone antagonists to shut down the production of testosterone through the reproductive system. It is the first drug to receive U.S. Food & Drug Administration approval for the treatment of nonmetastatic, castration-resistant prostate cancer. This article reviews the pharmacology of apalutamide along with its current place in therapy and management of associated adverse events.

There is no standard therapy for refractory acute myeloid leukemia (AML), but several salvage therapies are available (National Comprehensive Cancer Network [NCCN], 2018). Recently, there have been major developments in the treatment of AML focusing on the development of targeted and novel therapies. Ivosidenib is the first approved oral, targeted, small-molecule inhibitor of the isocitrate dehydrogenase 1 (IDH1) mutation seen in AML. IDH1 mutations have been associated with significantly worse outcomes in disease-free survival, relapse-free survival, and overall survival (NCCN, 2018). This article reviews the clinical trials and dose escalation studies that led to the U.S. Food & Drug Administration approval for ivosidenib in patients with relapsed or refractory AML with a susceptible IDH1 mutation. Patient counseling and monitoring, including dosing and administration, are important steps that advanced practitioners should be aware of. The mechanism of action and pharmacokinetic information for ivosidenib is discussed, as well as recommendations for drug-drug interaction management. Adverse events and monitoring parameters are addressed in detail, as well as how to interrupt and resume treatment due to adverse events.

Sickle cell disease (SCD) affects millions of people throughout the world. Hemoglobin S (HbS) polymerization is the fundamental cause of SCD pathophysiology, which leads to hemolysis, increased viscosity, and acute vaso-occlusive episodes. Novel agents have been developed to target the pathophysiology of SCD and decrease the frequency of SCD complications. Voxelotor (Oxbryta) is an HbS polymerization inhibitor that is approved by the U.S. Food & Drug Administration for the treatment of SCD in adults and pediatric patients 12 years and older.

In the United States, 1 in 8 women will be diagnosed with invasive breast cancer in her lifetime. Breast cancer death rates are higher for women in the United States than any other cancer, followed by lung cancer (National Cancer Institute, 2019). More than 70% of breast cancers are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, and of those patients, 40% have driver mutations in the gene phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) resulting in damaged phosphatidylinositol 3-kinase (PI3K) and uncontrolled cell growth (Mollon et al., 2018; Setiawan et al., 2009). These patients are initially treated with endocrine therapy, but resistance remains an issue. Inhibition of PI3K is a promising new approach to overcome resistance to endocrine therapy in breast cancer. Previous trials of PI3K inhibitors (pictilisib [GDC-0941], buparlisib [BMK120], and taselisib [GDC-0032]) in breast cancer have shown little efficacy secondary to toxicities due to their nonselectivity to PI3K subunits. Alpelisib is a selective inhibitor of PI3K for patients with HR-positive, HER2-negative, PIK3CA-mutated breast cancer who have progressed on endocrine therapy. This drug review will discuss the pharmacology of alpelisib, current data supporting its place in therapy, management of adverse events, and the clinical implications for advanced practitioners treating patients with HR-positive, HER2-negative breast cancer.

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma. Although 5-year survival rates in the first-line setting can range from 60% to 70%, up to 50% of patients become refractory or relapse after treatment (Crump et al., 2017). The standard treatment for relapsed/refractory diffuse large B-cell lymphoma is salvage chemotherapy followed by autologous stem cell transplant. Nonetheless, over 60% of patients are transplant ineligible, and there is currently no standard treatment option for these patients (Sarkozy & Sehn, 2018). Age, comorbidities, performance status, and disease deemed not responsive to chemotherapy conditioning are various factors potentially disqualifying patients for transplant. There is a strong demand for novel therapies. Polatuzumab vedotin, a targeted immunotherapy, was approved in 2019 by the U.S. Food & Drug Administration for the treatment of relapsed/refractory diffuse large B-cell lymphoma and is recommended by the National Comprehensive Cancer Network for patients who are transplant ineligible. This article reviews the pharmacology of polatuzumab vedotin, along with its performance in clinical trials, financial considerations, and management of adverse effects.

Acute myeloid leukemia (AML) is an aggressive myeloid disorder that is associated with a generally poor prognosis. Effective treatment options have been limited for older patients with AML who are not able to undergo intensive remission induction chemotherapy due to advanced age or comorbidities. New and novel agents are needed to improve treatment outcomes for this patient population. Glasdegib is a novel Hedgehog signaling pathway inhibitor approved by the U.S. Food & Drug Administration for the treatment of patients with newly diagnosed AML who are 75 years of age or older or who have comorbidities that preclude intensive induction chemotherapy. Glasdegib is approved in combination with low-dose cytarabine (LDAC). This approval is based on the results of a multicenter, open-label, randomized trial of glasdegib plus LDAC vs. LDAC monotherapy in which the addition of glasdegib resulted in an improvement in median overall survival.

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 CAR T-cell therapy that has demonstrated efficacy in relapsed and refractory diffuse large B-cell lymphoma (DLBCL) patients who have had suboptimal responses to conventional therapies. The immune activation that confers the efficacy of axi-cel comes at the price of potentially devastating adverse phenomena: cytokine release syndrome and neurotoxicity. This article serves as an overview of axi-cel, including a review of the available clinical evidence, mechanism of action, and management of some of the unique toxicities of axi-cel.

Mogamulizumab-kpkc provides a novel mechanism of action for the treatment of mycosis fungoides and Sézary syndrome. The efficacy and safety of mogamulizumab-kpkc for the treatment of relapsed or refractory mycosis fungoides and Sézary syndrome were demonstrated in a multicenter, open-label, randomized phase III trial comparing mogamulizumab-kpkc with vorinostat. Patients treated with mogamulizumab-kpkc showed a statistically significant increased progression-free survival (PFS; 7.7 months) compared with vorinostat (3.1 months). Overall response rates were higher with mogamulizumab-kpkc compared with vorinostat (28% vs. 5%; p < .0001). The most common adverse events (> 20%) associated with mogamulizumab-kpkc include rash, infusion-related reaction, fatigue, diarrhea, musculoskeletal pain, and upper respiratory tract infection. The use of mogamulizumab-kpkc up to 50 days prior to allogeneic hematopoietic stem cell transplantation has been associated with an increased risk of severe acute graft-vs.-host disease, steroid-refractory graft-vs.-host disease, and mortality. Additional labeled warnings include dermatologic toxicity, infection, and autoimmune complications. The overall benefit to risk assessment of mogamulizumab-kpkc is acceptable, but its use is constrained by the high cost of treatment and the short-term benefit.

The phosphoinositide 3-kinase (PI3K) pathway plays a primary role in cellular proliferation and metabolism. Inhibition of the PI3K pathway is an emerging area of drug development and cancer research. Idelalisib, copanlisib, and duvelisib are currently the only U.S. Food & Drug Administration–approved PI3K inhibitors available for use in hematologic malignancies. These PI3K inhibitors differ in their recommended indications, selectivity of PI3K isoforms, dosing, and potential toxicities. Several ongoing studies are aiming to expand the use of such drugs and identify unique combination regimens. This article discusses the current data supporting their place in therapy for B-cell malignancies, management of adverse events, and the clinical implications for advanced practitioners for the commercially available PI3K inhibitors.

Rucaparib and niraparib are two of the newest U.S. Food and Drug Administration–approved PARP inhibitors, joining olaparib with indications in ovarian cancer. Both drugs have led to meaningful responses when used as monotherapy in previously treated ovarian cancers, with niraparib demonstrating activity in both BRCA-mutated and BRCA wild-type tumors. Both rucaparib and niraparib have remarkably increased progression-free survival as maintenance therapy for patients with relapsed, platinum-sensitive epithelial ovarian cancer who responded to their most recent platinum-based regimen. In this setting, these drugs appear to be similar in efficacy but have distinct pharmacokinetic and adverse effect profiles. This article will guide the advanced practitioner through the efficacy, safety, and pharmacologic profiles of rucaparib and niraparib, while benchmarking them against olaparib for the treatment of ovarian cancer.