MedicalResearch.com Interview with:
Dr. Javier Gómez García
Senior Manager. Biostatistics and Data Management
PharmaMar
Madrid Area, Spain
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Multiple myeloma accounts for approximately 1 percent of all cancers and slightly more than 10 percent of all hematologic malignancies. At present, more than 80,000 new cases are reported worldwide each year, and the disease prevalence is increasing.
Plitidepsin is a synthetic cyclic depsipeptide isolated from the marine tunicate Aplidium albicans targeting the proto-oncogene eEF1A2, which is over-expressed in multiple myeloma cells.
In ADMYRE trial 255 relapsed and refractory multiple myeloma patients with at least three but not more than six prior regimens, including at least bortezomib and lenalidomide/thalidomide, were randomized at 2:1 ratio to receive plitidepsin 5 mg/m
2 D1 and 15 plus DXM 40 mg D1, 8, 15 and 22 (P+DXM), or DXM 40 mg D1,8,15 and 22 (DXM) every four weeks.
P+DXM met the primary endpoint, progression-free survival (PFS) assessed by an Independent Review Committee, showing a 35% risk reduction in the probability of progression or death. Indeed, a 20% risk reduction in the probability of death was also observed in spite of the fact that 44% of patients from control arm (DXM) switched to P+DXM arm after progression. Therefore, survival in the control arm might have been extended by the effect of plitidepsin, increasing the post progression survival and overestimating the survival observed in the control arm and consequently underestimating the actual difference between treatment arms.
Several methods were used to assess the impact of crossover and the robustness of the results even when penalizations were applied; PharmaMar believes that strong evidence in terms of survival benefit in favour of P+DXM has been established.
Naoto Tada Ueno, M.D., Ph.D., F.A.C.P.
Executive Director, Morgan Welch Inflammatory Breast Cancer Research Program and Clinic
Section Chief, Section of Translational Breast Cancer Research, Department of Breast Medical Oncology
Division of Cancer Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The best outcome of inflammatory breast cancer (IBC) is dependent on achieving a pathological completed response after neoadjuvant chemotherapy for primary inflammatory breast cancer, which is the most aggressive type of breast cancer.
We have conducted extensive preclinical work, which showed that EGFR is a potential therapeutic targets of IBC.
Based on this preclinical data, we have conducted a phase II study to determine the pathological complete response rate of panitumumab plus neoadjuvant chemotherapy for HER2 negative primary inflammatory breast cancer. 
Rebecca Ivy Hartman, M.D
Instructor in Dermatology
Brigham and Women's Hospital
Boston MA 02115
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Organ transplant recipients (OTR) are at 100-fold higher risk to develop certain skin cancers compared to the general population due to immunosuppression, and thus preventing skin cancer in this population is critical.
Our study found that in a high-risk Australian OTR population, only half of patients practiced multiple measures of sun protection regularly.
However, after participating in a research study that required dermatology visits, patients were over 4-times more likely to report using multiple measures of sun protection regularly. Patients were more likely to have a positive behavioral change if they did not already undergo annual skin cancer screening prior to study participation.
Dr. Jerusalem[/caption]
Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.
The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).
A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design. 
