Newly approved anti-CD19 monoclonal antibodies for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

Objective: This article summarizes the background, clinical trials, and place in therapy for the first two anti-CD19 monoclonal antibodies that have been recently FDA approved for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Summary: Treatment options are limited for patients that have relapsed after or are ineligible for autologous stem cell transplant (ASCT) or chimeric antigen receptor (CAR) T-cell therapy. Recent novel therapy approvals have started to change management strategies and outcomes for these patients. Two examples of recent FDA approvals are tafasitamab and loncastuximab tesirine, which represent the first anti-CD19 targeting monoclonal antibodies for patients with R/R DLBCL. Tafasitamab was granted accelerated approval in combination with lenalidomide for adult patients with R/R DLBCL after one or more lines of therapy based on the phase 2, L-MIND trial. Loncastuximab tesirine was granted accelerated approval for adult patients with R/R DLBCL after two or more lines of therapy based on the phase 2, LOTIS-2 trial. The place in therapy and sequencing of these agents can present a challenge to prescribers especially in regards to patients being evaluated for CD19 targeting CAR T-cell therapy. Conclusion: Tafasitamab and loncastuximab tesirine are options for use in patients with R/R DLBCL and are welcome additions to the limited therapy options for these patients. Further data is needed to elucidate sequencing and the impact these agents may have on CAR T-cell therapy. Ongoing clinical trials are studying these agents in the upfront setting in combination with other chemoimmunotherapy agents which may further expand treatment options for patients with B-cell lymphomas.

Immune checkpoint inhibitors: Significant advancements in non-small cell lung cancer treatment.

PURPOSE: This article explores the efficacy, toxicity, place in therapy, and considerations for use of recently approved immune checkpoint inhibitors (ICIs) in the treatment of non-small cell lung cancer (NSCLC). SUMMARY: Lung cancer is the leading cause of cancer mortality in the United States and is responsible for more cancer-related deaths than breast, prostate, and colorectal cancer combined. The landscape for lung cancer treatment is evolving with the approval of new and exciting novel therapies. Within the last decade numerous ICIs have been approved for use in the management of the most common subtype of lung cancer, NSCLC. The ICI agents currently approved by the Food and Drug Administration (FDA) for use in NSCLC include ipilimumab, pembrolizumab, nivolumab, durvalumab, and atezolizumab. These agents are approved for specific indications; therefore, they are not interchangeable. This review focuses on the landmark trials that led to each FDA-approved indication, as well as common toxicities seen with use of these agents. It also discusses the use of ICIs in special populations and unique considerations prior to initiation of treatment with these novel therapies in a patient with NSCLC. CONCLUSION: ICIs can provide a breakthrough treatment option for the management of NSCLC and are rapidly being adopted into clinical practice. It is important to be familiar with appropriate selection of an ICI therapy option for each patient based on approved indication, unique considerations, and anticipated toxicities.

Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: A retrospective analysis from a large academic medical center.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens. METHODS: This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron. RESULTS: A total of 268 eligible patients were included in the study. Eighty-eight patients received palonosetron and 180 patients received granisetron as their 5-HT3 receptor antagonist between October 31, 2014 and October 31, 2016. There were no statistically significant differences between the two antiemetic groups for the primary outcome of presence of any change in day 1 intravenous prophylactic antiemetics. Nine (10.23%) palonosetron patients and 15 (8.33%) granisetron patients required a change in their day 1 intravenous prophylactic antiemetics (P = 0.610). CONCLUSIONS: Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.

Preclinical and Dose-Finding Phase I Trial Results of Combined Treatment with a TORC1/2 Inhibitor (TAK-228) and Aurora A Kinase Inhibitor (Alisertib) in Solid Tumors.

PURPOSE: The purpose of this study was to evaluate the rational combination of TORC1/2 inhibitor TAK-228 and Aurora A kinase inhibitor alisertib in preclinical models of triple-negative breast cancer (TNBC) and to conduct a phase I dose escalation trial in patients with advanced solid tumors. EXPERIMENTAL DESIGN: TNBC cell lines and patient-derived xenograft (PDX) models were treated with alisertib, TAK-228, or the combination and evaluated for changes in proliferation, cell cycle, mTOR pathway modulation, and terminal cellular fate, including apoptosis and senescence. A phase I clinical trial was conducted in patients with advanced solid tumors treated with escalating doses of alisertib and TAK-228 using a 3+3 design to determine the maximum tolerated dose (MTD). RESULTS: The combination of TAK-228 and alisertib resulted in decreased proliferation and cell-cycle arrest in TNBC cell lines. Treatment of TNBC PDX models resulted in significant tumor growth inhibition and increased apoptosis with the combination. In the phase I dose escalation study, 18 patients with refractory solid tumors were enrolled. The MTD was alisertib 30 mg b.i.d. days 1 to 7 of a 21-day cycle and TAK-228 2 mg daily, continuous dosing. The most common treatment-related adverse events were neutropenia, fatigue, nausea, rash, mucositis, and alopecia. CONCLUSIONS: The addition of TAK-228 to alisertib potentiates the antitumor activity of alisertib in vivo, resulting in increased cell death and apoptosis. The combination is tolerable in patients with advanced solid tumors and should be evaluated further in expansion cohorts with additional pharmacodynamic assessment.

Evaluation of fosaprepitant-associated hypersensitivity reactions at a National Cancer Center.

INTRODUCTION: At our institution, an increased incidence of hypersensitivity reactions was reported following standardization of fosaprepitant as the preferred agent for the prophylaxis of chemotherapy induced nausea and vomiting (CINV) caused by highly emetogenic therapies. The purpose of this evaluation was to assess the incidence of systemic hypersensitivity reactions (HSRs) to fosaprepitant infusions compared to available literature. METHODS: This evaluation is a retrospective review of electronic health records of adult patients who received their first dose of fosaprepitant for CINV prophylaxis beginning January 1, 2017 through June 30, 2017 at the University of Colorado Cancer Center outpatient infusion center. Subjects were identified using medication administration reports. Individual chart reviews were performed for all patients who received fosaprepitant during the specified timeframe and had a reaction reported on the same date. RESULTS: A total of 868 patients received fosaprepitant in the outpatient infusion center during the study time period. Four patients (0.461%) had a systemic HSR attributed to fosaprepitant. Two of the reactions were reported as HSRs in the adverse reaction reporting system and two were found in provider notes during chart review. Due to the small sample size, risk factors for HSRs to fosaprepitant were not able to be determined. CONCLUSION: The incidence of HSRs to fosaprepitant at our institution was found to be consistent with the <1% incidence currently noted in literature. Based on these findings, opportunities have been identified for education on fosaprepitant-associated HSRs, proper documentation and patient-specific precautions.

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer.

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan. Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for 'sacituzumab govitecan' and 'clinical trial'. Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.

Apalutamide: A new agent in the management of prostate cancer.

Apalutamide is a competitive inhibitor of the androgen receptor and binds directly to the ligand-binding domain. The US Food and Drug Administration approved apalutamide on 14 February 2018 for use in patients with nonmetastatic castration-resistant prostate cancer based upon results from the phase III SPARTAN trial demonstrating significantly longer metastasis-free survival over placebo. The SPARTAN trial evaluated 1207 patients with nonmetastatic castration-resistant prostate cancer who were randomized 2:1 to apalutamide or placebo in combination with androgen deprivation therapy. Patients who received apalutamide experienced statistically significantly longer metastasis-free survival (40.5 versus 16.2 months, hazard ratio 0.28 (95% confidence interval = 0.23-0.35); P < 0.0001), which was the major efficacy outcome. Rash, hypothyroidism, and fracture were reported to occur more frequently with apalutamide than placebo. Based upon these results, apalutamide was deemed a safe and effective treatment option for patients with nonmetastatic castration-resistant prostate cancer. Clinical trials are ongoing to expand its indication in the metastatic setting, and identify additional roles for apalutamide in the management of prostate cancer such as in the castrate-sensitive metastatic setting.

Gemtuzumab Ozogamicin: Back Again.

Despite the recent onslaught of approved medications in oncology, acute myeloid leukemia (AML) has been a disease state bereft of pharmaceutical development for decades. The long-standing first-line regimen, 7 + 3, was developed in 1973. A group of four physicians at Roswell Park Memorial Institute built upon prior combinations of daunorubicin and cytarabine to find the optimal combination of 7 days of cytarabine and 3 days of daunorubicin (Lichtman, 2013). This regimen has undergone multiple modifications and patient performance status-based stratifications, but has remained the first-line therapy for AML for the past 45 years. In September 2017, gemtuzumab ozogamicin returned to market and shortly thereafter was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for AML, to be administered in combination with 7 + 3, and as monotherapy for both newly diagnosed and relapsed patients with acute myeloid leukemia (NCCN, 2018; US Food & Drug Administration, 2017). Gemtuzumab ozogamicin continues to be explored in various leukemia settings and is a welcomed addition to the currently available treatment options for AML.

Pilot Prehabilitation Program for Patients With Esophageal Cancer During Neoadjuvant Therapy and Surgery.

BACKGROUND: Locally advanced esophageal cancer is often treated with neoadjuvant therapy followed by surgery. Many patients present with or experience clinical deconditioning during neoadjuvant therapy. Prehabilitation programs in other areas of surgery have demonstrated improved postoperative outcomes. The aims of this study were to evaluate the feasibility of a pilot prehabilitation program and determine preliminary effects on surgical and cancer-related outcomes. METHODS: A retrospective review of patients treated at a single institution with resectable esophageal cancer was performed (n = 22). Patients in the prehabilitation group received protocol-structured intervention in several clinical domains including nutrition, psychosocial support, and physical exercise. RESULTS: Clinical stage and comorbidities were well matched between groups. The structured prehabilitation program was feasible and well received by participants. Fewer patients required admission during neoadjuvant therapy in the prehabilitation group (27.3% versus 54.5%). Percentage weight loss during treatment was 3.0% in the prehabilitation group versus 4.3% in the control group. Compared with the control group, the prehabilitation group demonstrated 0.0% versus 18.2% 30-d postoperative readmission rate and 18.2% versus 27.3% 90-d postoperative readmission rate. There were no statistically significant differences between groups in regard to complications or mortality. CONCLUSIONS: The pilot prehabilitation program demonstrated feasibility of implementing a structured program for patients receiving neoadjuvant therapy for esophageal cancer. Although the small population limits evaluation of statistical significance, trends in the data suggest a potential benefit of the prehabilitation program on neoadjuvant hospital admission rates, postsurgical readmission rates, and nutritional status.

A Review of PI3K Inhibitors in B-Cell Malignancies.

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.

Clinical pharmacy academic career transitions: Viewpoints from the field.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation, and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the fieldPart 1: Understanding feedback, evaluation, and advancement.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is a three-part commentary series that explores select challenges: 1) feedback, evaluation and advancement; 2) understanding and balancing of distribution of effort; 3) learning how and when to say yes. Faculty, or those interested in pursuing a career in pharmacy academia, can refer to this commentary series as a reference. Schools of pharmacy may utilize this as a tool for new faculty members during orientation in order to ensure smooth integration into the academic environment.

Clinical pharmacy academic career transitions: Viewpoints from the field Part 2: Understanding and balancing the distribution of effort.

INTRODUCTION: The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. The authors represent faculty members teaching within a large, state-funded, research-intensive School of Pharmacy located within a large academic health center. The authors have various backgrounds and represent individuals making transitions at various points in their careers (from residency into academia, from a non-academic environment into academia, and from one academic environment to another). COMMENTARY: This is Part 2 of a three-part commentary series that focuses on understanding and balancing the distribution of effort. Parts 1 and 3 of this commentary series explore feedback, evaluation and advancement; and learning when and how to say yes, respectively. While the entire series is intended to be read in continuity, faculty, or those interested in pursuing a career in pharmacy academia, can refer to Part 2 as a reference to aid in understanding and balancing the different components and the distribution of effort associated with a position in academic pharmacy, specifically. IMPLICATIONS: Schools of Pharmacy may utilize this as a tool for new faculty members during orientation in order to help ensure faculty success.

Clinical pharmacy academic career transitions: Viewpoints from the field part 3: Learning when and how to say yes.

The six authors of this commentary series, who have recently transitioned into or within an academic career, discuss challenging aspects of an academic career change. This is Part 3 of a three-part commentary series that focuses on when and how to say yes to the multitude of opportunities available to pharmacy practice faculty. Part 1 discusses feedback, evaluation, and advancement. Part 2 explains distribution of effort (DOE) and how to marry the different components of teaching, research, and service. While the entire series is intended to be read in continuity, faculty, or those interested in pursuing a career in pharmacy academia, can refer to Part 3 as a reference on how to screen opportunities within academia to maximize professional and personal growth and minimize career burnout. Schools of pharmacy may utilize this as a tool for new faculty members during orientation to help ensure faculty success.

Ublituximab for the treatment of CD20 positive B-cell malignancies.

INTRODUCTION: Non-Hodgkin lymphoma (NHL) is the most common adult hematologic malignancy. Conventional methods of treatment are chemotherapy and radiation, which were associated with toxicities and lack of specificity. Potential cell surface targets for treatment of B-cell NHL (B-NHL) include CD19, CD20, and CD22 which are highly expressed on malignant B-cells. The development of monoclonal antibody (mAb) therapy directed against CD20 had the most clinical impact in the treatment of B-NHL. Early clinical trials with rituximab (RTX), the first chimeric mAb against CD20, showed efficacy and minimal toxicities. RTX was later approved as first line in combination with CHOP chemotherapy for Diffuse Large B-NHL (DLBCL). The emergence of resistance to RTX prompted the development of the next-generation of mAbs targeting CD20 (e.g. obinituzumab, ofatumumab), and includes ublituximab (Ub), with higher complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) against malignant B-cells. Areas covered: Herein, we discuss clinical trials of Ub, highlighting efficacy, tolerability and an expert opinion on drug development in B-NHL. A pubmed search was conducted to evaluate all Ub clinical trials. Expert opinion: Ub demonstrated efficacy in patients with high-risk CLL and B-NHL in both first line, subsequent lines, and in rituximab refractory patients.

Collaboration Leads to Oral Chemotherapy Education.

The Association of Community Cancer Centers (ACCC), Hematology/Oncology Pharmacy Association (HOPA), National Community Oncology Dispensing Association (NCODA), and Oncology Nursing Society (ONS) partnered together to create a resource for providers, and patients and caregivers on oral chemotherapy agents. The patient education sheets include information on medication names and pronunciation, approved uses, dose and schedule, drug and food interactions, the best practice guidelines for safe handling, administration, and disposal of oral chemotherapy agenzts by patients and caregivers; management strategies for the most common side effects; and pregnancy, sexual activity, and contraception information. Each sheet also has an area to list from which pharmacy the patient will receive the medication. The document and the website also provide the link to the individual product website, prescribing information, and product resources, if available.

Rising Cost of Cancer Pharmaceuticals: Cost Issues and Interventions to Control Costs.

The rising cost of pharmaceuticals and, in particular, cancer drugs has made headline news in recent years. Several factors contribute to increasing costs and the burden this places on the health care system and patients. Some of these factors include costly cancer pharmaceutical research and development, longer clinical trials required to achieve drug approval, manufacturing costs for complex compounds, and the economic principles surrounding oncology drug pricing. Strategies to control costs have been proposed, and some have already been implemented to mitigate cancer drug costs such as the use of clinical treatment pathways and tools to facilitate cost discussions with patients. In this article, we briefly review some of the potential factors contributing to increasing cancer pharmaceutical costs and interventions to mitigate costs, and touch on the role of health care providers in addressing this important issue.

Dronabinol for chemotherapy-induced nausea and vomiting unresponsive to antiemetics.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common symptoms feared by patients, but may be prevented or lessened with appropriate medications. Several antiemetic options exist to manage CINV. Corticosteroids, serotonin receptor antagonists, and neurokinin receptor antagonists are the classes most commonly used in the prevention of CINV. There are many alternative drug classes utilized for the prevention and management of CINV such as antihistamines, benzodiazepines, anticonvulsants, cannabinoids, and dopamine receptor antagonists. Medications belonging to these classes generally have lower efficacy and are associated with more adverse effects. They are also not as well studied compared to the aforementioned agents. This review will focus on dronabinol, a member of the cannabinoid class, and its role in CINV. Cannabis sativa L. (also known as marijuana) contains naturally occurring delta-9-tetrahydrocannibinol (delta-9-THC). The synthetic version of delta-9-THC is the active ingredient in dronabinol that makes dronabinol an orally active cannabinoid. Evidence for clinical efficacy of dronabinol will be analyzed in this review as monotherapy, in combination with ondansetron, and in combination with prochlorperazine.

Ramucirumab: A vascular endothelial growth factor receptor-2 inhibitor with activity in several malignancies.

PURPOSE: The pharmacology, pharmacokinetics, safety, dosage and administration, current and potential roles in therapy, and cost considerations of ramucirumab are reviewed. SUMMARY: Ramucirumab is a recombinant monoclonal antibody that selectively inhibits vascular endothelial growth factor receptor-2. Ramucirumab has been approved for the treatment of gastric cancer, non-small-cell lung cancer (NSCLC), and metastatic colorectal cancer. Ramucirumab displays similar pharmacokinetics in patients with gastric cancer, NSCLC, and metastatic colorectal cancer. The most common adverse effects of any grade with ramucirumab monotherapy included fatigue, decreased appetite, abdominal pain, hypertension, anemia, hemorrhage, and diarrhea. For ramucirumab monotherapy in patients with gastric cancer, ramucirumab 8 mg/kg should be administered by i.v. infusion every two weeks. For combination therapy, ramucirumab should be administered at the same dose with weekly paclitaxel 80 mg/m(2) i.v. on days 1, 8, and 15 every 28 days. When treating NSCLC, the recommended ramucirumab dose is 10 mg/kg i.v. with docetaxel 75 mg/m(2) i.v. on day 1 every 21 days. For combination therapy with FOLFIRI (fluorouracil, leucovorin, and irinotecan) for metastatic colorectal cancer, ramucirumab 8 mg/kg should be administered by i.v. infusion every two weeks. The average wholesale prices of ramucirumab are $1224 and $6120 for the 100- and 500-mg single-dose vials, respectively. CONCLUSION: Ramucirumab has demonstrated benefit in a variety of cancers, supporting the role of antiangiogenic agents in the management of malignancies. However, the clinical benefit in certain malignancies may be offset by the high cost of ramucirumab and the duration of treatment.