A practical guide for the safe implementation of early phase drug development and immunotherapy program in gynecologic oncology practice.

The success of targeted and immune therapies in other malignancies has led to an exponential increase in the number of active and pending clinical trials using these therapeutic approaches in patients with gynecologic cancers. These novel investigational agents are associated with unique and potentially life-threatening toxicities and many require special multidisciplinary logistical considerations. The objective of this review is to describe a practical approach for the safe implementation of targeted and immune therapies in academic gynecologic oncology practices based on our experience at M.D. Anderson Cancer Center.

Dabrafenib therapy for advanced melanoma.

OBJECTIVE: To summarize the clinical development of dabrafenib and to highlight the clinically relevant distinct characteristics of dabrafenib in contrast to vemurafenib. DATA SOURCE: An English-language literature search of MEDLINE/PubMed (1966-June 2013), using the keywords GSK2118436, dabrafenib, vemurafenib, selective BRAF inhibitor, and advanced melanoma, was conducted. Data were also obtained from package inserts, meeting abstracts, and clinical registries. STUDY SELECTION AND DATA EXTRACTION: All relevant published articles on dabrafenib and vemurafenib were reviewed. Clinical trial registries and meeting abstracts were used for information about ongoing studies. DATA SYNTHESIS: BRAF(V600E) mutation confers constitutive BRAK kinase activation in melanoma cells, promoting tumor growth. This discovery led to the development of BRAF kinase inhibitors like vemurafenib and dabrafenib. Dabrafenib has been approved to treat patients with BRAF(V600E)-positive unresectable or metastatic melanoma based on its clinical benefit demonstrated in a randomized phase III study. It has also been shown to be safe and effective in patients with BRAF mutant advanced melanoma involving the brain. Dabrafenib is well tolerated, with the most common adverse effects being hyperkeratosis, headache, pyrexia, and arthralgia. Currently, there is no evidence to suggest that one BRAF inhibitor is superior to the other. With similar efficacy, therapy selection will likely be influenced by differential tolerability and cost. CONCLUSIONS: Dabrafenib joins vemurafenib to confirm the superior clinical outcome of the BRAF inhibitors when compared with dacarbazine in patients with BRAF(V600E)-positive advanced melanoma. Active research is ongoing to expand its utility into the adjuvant setting and to circumvent rapid emergence of drug resistance.

New and emerging therapies for advanced or metastatic soft tissue sarcoma.

Soft tissue sarcomas include a rare variety of tumors, which require a multidisciplinary approach to treatment. Patients with advanced or metastatic disease are typically treated with anthracycline-based therapy, but these chemotherapy regimens are associated with poor response rates and average survival duration of one year. Much attention has been turned toward overexpressed gene pathways, and utilizing targeted therapies to inhibit tumor growth. Many new and approved targeted therapies and chemotherapy agents are currently in clinical and preclinical studies for soft tissue sarcoma. As the results of these studies are reported, we hope to see improved response rates and less toxicity, both in the frontline setting and for patients with advanced disease. This article will review the available data for some of the more promising therapies for advanced or metastatic soft tissue sarcomas.

Tools to expedite the development of treatment plans.

Quality improvement strategies can be used to modify existing health care processes to reduce patient wait times. We undertook a quality improvement project to reduce the time between new patients' initial visits and the finalization of their treatment plans. Initiation of treatment of new patients at the MD Anderson Sarcoma Medical Oncology Clinic can take up to 2 weeks from their initial consultation. Treatment delays result in increased costs and anxiety for the patient, adversely affecting the quality of care provided. We performed detailed process mapping and a cause-and-effect analysis to identify and prioritize opportunities for improvement. Process improvements addressed 2 key causes of delay to develop a finalized treatment plan: (1) insufficient data for decision making at the time of new patient visit and (2) delays in obtaining diagnostic imaging. After implementing our process improvements, the median time to develop a treatment plan decreased by 89% from 70.5 to 7.6 hours. Our process changes involved minimal additional work and had the secondary outcome of resulting in time savings for the clinic team.