Type 1 insulin like growth factor receptor (IGF-1R) targeted therapies showed compelling pre-clinical evidence; however, to date, this has failed to translate into patient benefit in Phase 2/3 trials in unselected patients. This was further complicated by the toxicity, including hyperglycemia, which largely results from the overlap between IGF and insulin signaling systems and associated feedback mechanisms. This has halted the clinical development of inhibitors targeting IGF signaling, which has limited the availability of biopsy samples for correlative studies to understand biomarkers of response. Indeed, a major factor contributing to lack of clinical benefit of IGF targeting agents has been difficulty in identifying patients with tumors driven by IGF signaling due to the lack of predictive biomarkers. In this review, we will describe the IGF system, rationale for targeting IGF signaling, the potential liabilities of targeting strategies, and potential biomarkers that may improve success.

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Aims: Clinical decision making is challenging in men with metastatic prostate cancer (mPC), as heterogeneity in treatment options and patient characteristics have resulted in multiple scenarios with little or no evidence. The South East Asia Expert Panel 2019 addressed some of these challenges. Methods: Based on evidence in the literature and expert interviews, 19 statements were formulated for key challenges in the treatment of men with castration-sensitive and -resistant prostate cancer in clinical practice. A modified Delphi process was used to reach consensus among experts in the panel and develop clinical practice recommendations. Results: The majority of the panel preferred a risk-based stratification and recommended abiraterone or enzalutamide as first-line therapy for symptomatic chemotherapy naïve patients. Abiraterone is preferred over enzalutamide as a first-line treatment in these patients. However, the panel did not support the use of abiraterone in high risk lymph-node positive only (N+M0) or in non-metastatic (N0M0) patients. In select patients, low dose abiraterone with food may be used to optimize clinical outcomes. Androgen receptor gene splice variant status may be a useful guide to therapy. In addition, generic versions of approved therapies may improve access to treatment to a broader patient population. The choice of treatment, as well as sequencing are guided by both patient and disease characteristics, preferences, drug access, cost, and compliance. Conclusion: Expert recommendations are key to guidance for the optimal management of mPC. Appropriate choice, timing, and sequence of treatment options can help to tailor therapy to maximize outcomes in men with mPC.

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