Analysis by region of outcomes for patients with advanced renal cell carcinoma treated with cabozantinib or everolimus: a sub-analysis of the METEOR study.

INTRODUCTION: METEOR was a phase 3 trial (NCT01865747) of cabozantinib versus everolimus in adults with advanced or metastatic clear cell RCC previously treated with VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs). This post hoc analysis of METEOR compared outcomes for patients recruited from European and non-European countries. MATERIAL AND METHODS: Adults with advanced/metastatic clear cell RCC who had received ≥ 1 prior VEGFR-TKI treatment were randomized 1:1 to receive cabozantinib or everolimus. Patients were categorized by recruitment region: Europe or outside of Europe (rest of world [RoW]). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and adverse events (AEs) were compared between regional subgroups. RESULTS: In total, there were 320 eligible patients from Europe (cabozantinib, 167; everolimus, 153) and 338 from RoW (North America, 240 patients; Asia-Pacific, 86; Latin America, 12; randomized as cabozantinib, 163; everolimus, 175). PFS and OS were longer with cabozantinib than with everolimus and similar for the Europe and RoW subgroups. For PFS, the hazard ratio (HR) for cabozantinib versus everolimus was 0.54 for the Europe subgroup (p < .001) and 0.50 for the RoW subgroup (p < .001). For OS, the HR was 0.75 for the Europe subgroup (p = .034) and 0.69 for the RoW subgroup (p = .006). ORR in the Europe subgroup was 15% for cabozantinib and 3.9% for everolimus (p < .001). For the RoW subgroup, ORR was 20% for cabozantinib and 2.9% for everolimus (p < .001). Incidence of grade 3/4 AEs were similar for the Europe (cabozantinib, 74%; everolimus, 58%) and RoW subgroups (cabozantinib, 69%; everolimus, 64%). CONCLUSION: In the METEOR trial, efficacy outcomes for patients recruited from European and non-European countries favored cabozantinib over everolimus. The efficacy and safety results for the regional subgroups were consistent with those of the overall METEOR population.

High-dose chemotherapy plus stem cell transplantation in advanced germ cell cancer: a review.

CONTEXT: High-dose chemotherapy (HDCT) with stem cell transplantation (SCT) has been investigated as a treatment strategy for advanced germ cell cancer (GCC) for >2 decades. In an effort to improve on the overall cure rates of 80% achievable with conventional chemotherapy, researchers have investigated this therapeutic option as a first-line therapy for those with poor-prognosis disease and as a salvage therapy for those with relapsed or refractory disease. OBJECTIVE: The primary objective of this review is to define the role of HDCT plus SCT in advanced GCC. Prognostic indicators for this group of patients are also presented. EVIDENCE ACQUISITION: A Medline search of English-language literature was performed to identify studies published in the last 20 yr relating to the use of HDCT plus SCT in advanced GCC. Phase 1, phase 2, and phase 3 trials were included, as were retrospective reviews and meta-analyses. EVIDENCE SYNTHESIS: Phase 2 trials investigating HDCT plus SCT as a therapeutic option for advanced germ cell cancer have indicated a survival advantage over conventional chemotherapy. This has not been confirmed in the phase 3 setting. Alternative chemotherapeutic strategies and options following failure of HDCT plus SCT are discussed. CONCLUSIONS: Studies to date have not indicated a survival advantage for the use of HDCT plus SCT in advanced germ cell cancer. Many questions, however, remain unanswered, and further research is required to identify whether optimising the strategy of HDCT plus SCT will improve outcome in this predominantly young group of patients.

Optimal therapy for oesophageal cancer.

Oesophageal carcinoma is one of the commonest cancers in the world and has an increasing incidence in Western civilisation. As the epidemiology of the disease has changed so too has our treatment strategies. The present standard of care is surgery but this is associated with disappointing survival figures. The role of chemotherapy and radiation is now established in inoperable disease. How best to deliver these modes of therapy has yet to be defined. Extrapolation of data from previous trials is difficult as these trials have many deficiencies and do not account for recent advances in therapeutics or techniques of delivery. The role of chemo-radiotherapy in operable disease is even more controversial. A number of prospective randomised trials of trimodality therapy versus surgery alone suggests a benefit for multimodal therapy. These trials also reveal evidence to support the use of chemo-radiotherapy alone in a subset of patients with resectable disease. The appropriate application of these varied therapeutic interventions remains unanswered. Further progress in diagnostic techniques and predictive markers may allow us to stratify patients into different treatment groups. Continued investigation is required to keep pace with the evolution of oesophageal cancer and its therapy. This will facilitate a better understanding of the disease and optimise the treatment offered to patients.