Talimogene Laherparepvec: An Oncolytic Virus Therapy for Melanoma.

OBJECTIVE: To review the efficacy and safety of talimogene laherparepvec (T-VEC) as well as its pharmacology, pharmacokinetics, drug-drug interactions, handling procedures, cost considerations, and place in therapy. DATA SOURCES: Searches of PubMed (1966 to February 2017) and Cochrane Library (1999 to February 2017) were conducted using the terms talimogene laherparepvec, T-VEC, OncoVEX, immunotherapy, melanoma, and oncolytic virus. Additional information was determined from bibliographies, manufacturer product labeling and website, meeting abstracts, Food and Drug Administration website, and clinicaltrials.gov. STUDY SELECTION AND DATA EXTRACTION: A total of 79 English-language publications were identified. Articles that assessed T-VEC's pharmacokinetics, pharmacodynamics, mechanism, dosing, safety, and efficacy were included as well as narrative reviews that provided practical information. DATA SYNTHESIS: Clinical trials have confirmed the safety and efficacy of T-VEC as monotherapy for the treatment of advanced melanoma, with an overall response rate (ORR) of 26%. Relative to granulocyte-macrophage colony-stimulating factor, T-VEC significantly increased durable response rate (DRR; 16.3% vs 2.1%, P < 0.001); however, median overall survival was not improved (23.3 vs 18.9 months, P = 0.051). Phase 1b trials have combined T-VEC and immunotherapies with promising results. T-VEC's adverse effects are generally considered mild to moderate in severity. CONCLUSION: T-VEC is the first approved oncolytic virus for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in melanoma recurrent after initial surgery. T-VEC improves ORR and DRR as a single agent, shows promise in combination therapy, and is well tolerated. Ongoing trials will determine if T-VEC has a role in early treatment or in combination therapy for melanoma or other malignancies.

Evaluation of empiric antibiotic de-escalation in febrile neutropenia.

INTRODUCTION: Up until 2010, the recommended duration of empiric broad-spectrum antibiotics for febrile neutropenia was until absolute neutrophil count (ANC) recovery. An updated guideline on the use of antimicrobial agents in neutropenic patients with cancer indicates that patients who have completed an appropriate treatment course of broad-spectrum antibiotics, with resolution of signs and symptoms of infection but persistent neutropenia, can be de-escalated to oral fluoroquinolone prophylaxis until ANC recovery. METHODS: The primary objective of this retrospective investigation was to evaluate the safety and efficacy of de-escalating broad-spectrum antibiotics in patients remaining neutropenic after at least 14 days of empiric broadspectrum antibiotics for febrile neutropenia compared to patients continuing broad-spectrum antibiotics until ANC recovery. RESULTS: There were 16 patients (61.5%) in the comparator group who met the primary endpoint of remaining afebrile and without escalation of antibiotics for at least 72 hours after 14 days of broad-spectrum antibiotics and 21 patients (80.7%) in the de-escalation group who met the primary endpoint of remaining afebrile and without reinitiation of broad-spectrum antibiotics for at least 72 hours after de-escalation to levofloxacin therapy (p = 0.11). Mean total duration of broad-spectrum antibiotic therapy was 23.5 ± 1.5 days in the comparator group versus 22.2 ± 1.43 days in the de-escalation group (p = 0.39). CONCLUSIONS: Results of this investigation indicate that broad-spectrum antibiotics can be safely de-escalated to levofloxacin prophylaxis prior to ANC recovery in select patients. This practice may decrease the duration of broad-spectrum antibiotic exposure and associated complications.

Ado-trastuzumab emtansine: a HER2-positive targeted antibody-drug conjugate.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug-drug interactions, dosage and administration, and formulary considerations for ado-trastuzumab emtansine. DATA SOURCES: Sources of information were identified through a PubMed search (1966 to June 2014) using the key terms ado-trastuzumab emtansine, trastuzumab-DM1, trastuzumab-MCC-DM1, and T-DM1. Other information was obtained from clinicaltrials.gov, product labeling, and press releases. STUDY SELECTION AND DATA EXTRACTION: All English-language clinical trials and abstracts evaluating ado-trastuzumab emtansine in humans were reviewed for inclusion. DATA SYNTHESIS: Overexpression or amplification of human epidermal growth factor receptor 2 (HER2) occurs in approximately 20% of breast cancers and is associated with more aggressive tumors and poorer prognosis in the absence of treatment. Although effective therapies for the initial management of HER2-positive metastatic breast cancer (MBC) exist, many patients will experience disease progression. Most second-line therapies are associated with either significant toxicities or limited improvements in overall survival (OS). Ado-trastuzumab emtansine is a HER2-positive directed antibody drug conjugate (ADC) approved in February 2013. In phase III clinical trials comparing the efficacy and safety of ado-trastuzumab emtansine with lapatinib-capecitabine or physician's choice, ado-trastuzumab emtansine had a better tolerability profile and improved progression-free survival compared with lapatinib-capecitabine or physician's choice and increased OS compared with lapatinib-capecitabine. CONCLUSION: Ado-trastuzumab emtansine is a novel ADC effective for HER2-positive MBC in patients previously treated with trastuzumab, lapatinib, and a taxane. Further studies will determine its use in the adjuvant and neoadjuvant setting and in combination with pertuzumab.