Phase 1b clinical trial of ado-trastuzumab emtansine and ribociclib for HER2-positive metastatic breast cancer.

Patients with HER2+ metastatic breast cancer are often treated with a multitude of therapies in the metastatic setting, and additional strategies to prolong responses to anti-HER2 therapies are needed. Preclinical evidence suggests synergy between cyclin-dependent kinase 4 and 6 (CDK 4/6) inhibitors and anti-HER2 therapies. We conducted a phase 1b study of ribociclib and ado-trastuzumab emtansine (T-DM1) in patients with advanced/metastatic HER2-positive breast cancer previously treated with trastuzumab and a taxane in any setting, with four or fewer prior lines of therapy in the metastatic setting. A standard 3 + 3 dose-escalation design was used to evaluate various doses of ribociclib in combination with T-DM1, starting at 300 mg. The primary objective was to determine the maximum tolerated dose and/or recommended phase 2 dose (RP2D) of ribociclib in combination with T-DM1. A total of 12 patients were enrolled. During dose-escalation, patients received doses of ribociclib of 300 mg (n = 3), 400 mg (n = 3), 500 mg (n = 3), and 600 mg (n = 3). No dose-limiting toxicities were observed. The majority of toxicities were Grade 1 and 2, and the most common Grade 3 toxicities were neutropenia (33%), leukopenia (33%), and anemia (25%). After a median follow-up of 12.4 months, the median PFS was 10.4 months (95% confidence interval, 2.7-19.3). Based on the pharmacokinetic analysis, adverse events, and dose reductions, 400 mg was determined to be the RP2D for ribociclib given on days 8-21 of a 21-day cycle with T-DM1.

Sacituzumab Govitecan for Metastatic Triple-Negative Breast Cancer: Clinical Overview and Management of Potential Toxicities.

Patients with metastatic triple-negative breast cancer have a poor prognosis. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate that contains the irinotecan active metabolite, SN-38, linked to a humanized monoclonal antibody targeting trophoblast cell surface antigen 2, which is overexpressed in many solid tumors. In a basket design phase I/II study, sacituzumab govitecan demonstrated promising single-agent therapeutic activity in multiple cancer cohorts, leading to accelerated approval by the U.S. Food and Drug Administration of sacituzumab govitecan-hziy (TRODELVY) for the treatment of patients with metastatic triple-negative breast cancer who had received at least two prior therapies in the metastatic setting. Recently, results of the phase III trial, ASCENT, were confirmatory. There is limited available information on the adverse event management with sacituzumab govitecan needed to maximize the dose and duration of effective therapy while maintaining patient quality of life. This review summarizes the clinical development and the practical management of patients receiving sacituzumab govitecan. Sacituzumab govitecan has a well-defined and manageable toxicity profile, and rapid recognition and appropriate early and proactive management will allow clinicians to optimize sacituzumab govitecan treatment for patients. IMPLICATIONS FOR PRACTICE: Sacituzumab govitecan (TRODELVY) is a novel antibody-drug conjugate composed of the active metabolite of irinotecan (SN-38) conjugated to a monoclonal antibody targeting trophoblast cell surface antigen 2, an epithelial cell surface antigen overexpressed in many cancers. Because of the rapid approval of sacituzumab govitecan, there is limited available information on adverse event (AE) management with this agent. As such, this article reviews the clinical development of the drug, the AE profile, and provides recommendations regarding AE management to help optimize therapy with sacituzumab govitecan.

Cutaneous Metastases: A Case Study on Clinical Care for Patients.

Cutaneous metastases (CMs) signal the spread of a primary tumor to the skin and dermis, particularly in patients with melanoma or with breast, lung, or gastrointestinal cancers. Although these lesions may present as superficial and painless, some CMs may lead to ulceration, drainage, and discomfort, causing distress to patients. Oncology nurses require knowledge about the clinical presentation of CMs, including incidence, pathophysiology, diagnostic evaluation, and complex symptomatology, as well as standard treatment and care for patients. In addition, nurses can provide psychosocial interventions to assist patients experiencing distress from CM lesions.

Pilot Study of a Brief Behavioral Intervention for Dyspnea in Patients With Advanced Lung Cancer.

CONTEXT: Dyspnea is a common symptom in patients with advanced cancer that interferes with functional ability and quality of life (QOL). Although few evidence-based treatments for dyspnea exist, prior studies show support for nonpharmacological interventions that include elements of cognitive-behavioral therapy. OBJECTIVES: To examine the feasibility and utility of delivering a brief behavioral intervention for dyspnea in patients with lung cancer. METHODS: For this single-group pilot study, eligible patients included those with advanced lung cancer (Stage III or IV non-small cell or extensive-stage small cell lung cancer) receiving outpatient cancer treatment who reported at least moderate breathlessness. The manualized intervention consisted of two sessions in which nurse practitioners taught participants breathing and relaxation techniques within the infusion clinic and encouraged home practice. Participants completed measures of breathlessness (Modified Medical Research Council Dyspnea Scale), QOL (Functional Assessment of Cancer Therapy-Lung Trial Outcome Index), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale) at baseline and within six weeks after enrollment. RESULTS: Of the 32 patients enrolled in the study (56.3% females; mean age 63.34 [SD] = 7.96 years), 84.4% (N = 27) completed all study procedures. Comparing the baseline to postassessments, we found significant improvements in Modified Medical Research Council Dyspnea Scale (P < 0.001), Functional Assessment of Cancer Therapy-Lung Trial Outcome Index (P = 0.01), and Hospital Anxiety and Depression Scale-depression subscale (P < 0.001) scores. CONCLUSION: In this sample of patients with advanced lung cancer and dyspnea, we observed a high completion rate for the two-session behavioral intervention. Patients also reported improvements in dyspnea, QOL, and mood. Follow-up randomized controlled trials are needed to examine the efficacy of brief behavioral interventions for cancer-related dyspnea.

Phase II trial of thalidomide and carmustine for patients with recurrent high-grade gliomas.

PURPOSE: The use of thalidomide as an antiangiogenic agent has met with only limited success in the treatment of malignant gliomas. On the basis of preclinical data demonstrating synergistic antitumor activity when antiangiogenic agents are combined with cytotoxic agents, we explored the clinical activity of the combination of thalidomide and carmustine (BCNU) in patients with recurrent high-grade gliomas. PATIENTS AND METHODS: Patients with a histologic diagnosis of high-grade glioma and radiographic evidence of tumor progression after standard surgery, radiation, and chemotherapy were eligible for the study. Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of thalidomide that was escalated to a maximal dose of 1,200 mg/d as tolerated. RESULTS: A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were accrued to the study. The combination of thalidomide and BCNU was well tolerated; mild myelosuppression and mild to moderate sedation were the most common side effects. The median progression-free survival (100 days) and the objective radiographic response rate (24%) for patients with glioblastoma compared favorably with data from historical controls. CONCLUSION: This is one of the first clinical trials to evaluate the strategy of combining a putative antiangiogenic agent with a cytotoxic agent in patients with primary brain tumors. Our data demonstrate that thalidomide in combination with BCNU is well tolerated and has antitumor activity in patients with recurrent high-grade gliomas. Although the combination seems to be more active than either agent alone, such conclusions await confirmatory trials.