Megan Veresh Caram

Advanced or metastatic gastrointestinal stromal tumors: Systemic treatment options

Gastrointestinal stromal tumor (GIST), the most common sarcoma arising in the gastrointestinal tract, typically expresses the tyrosine‐kinase receptor, C‐KIT, and contains activating mutation in the c‐kit or platelet‐derived growth factor receptor (pdgfr) gene. Recently, development of small molecules that inhibit the kinase activity of mutant C‐KIT and PDGFR proteins has radically changed treatment and prognosis of patients diagnosed with advanced GIST as this molecularly “targeted” therapy has demonstrated remarkable high‐level of activity in this disease. J. Surg. Oncol. 2011; 104:888–895.

Targeting Androgen Receptor and DNA Repair in Metastatic Castration-Resistant Prostate Cancer: Results From NCI 9012

Purpose To determine whether cotargeting poly (ADP-ribose) polymerase-1 plus androgen receptor is superior to androgen receptor inhibition in metastatic castration-resistant prostate cancer (mCRPC) and whether ETS fusions predict response. Patients and Methods Patients underwent metastatic site biopsy and were stratified by ETS status and randomly assigned to abiraterone plus prednisone without (arm A) or with veliparib (arm B). Primary objectives were: confirmed prostate-specific antigen (PSA) response rate (RR) and whether ETS fusions predicted response. Secondary objectives were: safety, measurable disease RR (mRR), progression-free survival (PFS), and molecular biomarker analysis. A total of 148 patients were randomly assigned to detect a 20% PSA RR improvement. Results A total of 148 patients with mCRPC were randomly assigned: arm A, n = 72; arm B, n = 76. There were no differences in PSA RR (63.9% v 72.4%; P = .27), mRR (45.0% v 52.2%; P = .51), or median PFS (10.1 v 11 months; P = .99). ETS fusions did not predict response. Exploratory analysis of tumor sequencing (80 patients) revealed: 41 patients (51%) were ETS positive, 20 (25%) had DNA-damage repair defect (DRD), 41 (51%) had AR amplification or copy gain, 34 (43%) had PTEN mutation, 33 (41%) had TP53 mutation, 39 (49%) had PIK3CA pathway activation, and 12 (15%) had WNT pathway alteration. Patients with DRD had significantly higher PSA RR (90% v 56.7%; P = .007) and mRR (87.5% v 38.6%; P = .001), PSA decline ≥ 90% (75% v 25%; P = .001), and longer median PFS (14.5 v 8.1 months; P = .025) versus those with wild-type tumors. Median PFS was longer in patients with normal PTEN (13.5 v 6.7 months; P = .02), TP53 (13.5 v 7.7 months; P = .01), and PIK3CA (13.8 v 8.3 months; P = .03) versus those with mutation or activation. In multivariable analysis adjusting for clinical covariates, DRD association with PFS remained significant. Conclusion Veliparib and ETS status did not affect response. Exploratory analysis identified a novel DRD association with mCRPC outcomes.

Androgen-deprivation-associated bone disease.

Purpose of review Androgen deprivation therapy (ADT) remains a common treatment for prostate cancer, even in the nonmetastatic setting and in scenarios without evidence of efficacy. Increasing attention has focused on its adverse effects, of which bone disease in the form of osteoporosis and fractures has been one of the major concerns. Recently published articles are reviewed, focusing on ADT effects on bone and management of ADT-associated bone disease. Recent findings A range of strategies directed at ADT-associated bone disease are available, including antiresorptive agents such as denosumab and bisphosphonates, as well as complementary approaches such as calcium and vitamin D supplementation, exercise regimens, and multifaceted interventions incorporating several approaches. Most interventions used bone mineral density as a surrogate outcome, despite compelling evidence that it inadequately captures fracture risk. Summary The antiresorptive agents are clearly able to preserve bone mineral density in men on ADT, whereas other approaches have modest to no benefits. Unfortunately, despite intense research interest in this area, no approach has yet demonstrated a definitive and convincing reduction in clinically relevant fracture outcomes. This emphasizes the importance of restricting the use of ADT to settings in which its benefits are clearly established, in order to limit unnecessary complications.

Sarcopenia is associated with autologous transplant-related outcomes in patients with lymphoma

Sarcopenia is associated with treatment-related complications and shorter overall survival in patients with cancer. Psoas area indices were calculated for 121 patients with lymphoma who underwent autologous transplant. Controlling for age, body mass index, comorbidities and performance status for the 73 men included, the hazard ratio (95% confidence interval, CI) for non-relapse mortality was 2.37 (1.01, 5.58), p = 0.048 for every 100 unit decrease in total psoas index and 2.67 (1.04, 6.86), p = 0.041 for every 100 unit decrease in lean psoas index. Men with a lower total psoas index experienced more complications (p = 0.001) and spent more days in hospital (p = 0.03) during the transplant admission. A strong association existed between sarcopenia and number of hospital days in the 100 days following transplant among both men (p < 0.0001) and women (p < 0.0001). Sarcopenia may impact negative outcomes after autologous transplant thereby serving as a potentially modifiable predictor of outcomes and aiding in treatment selection.

The implications of baseline bone health assessment at initiation of androgen deprivation therapy for prostate cancer

To assess bone‐density testing (BDT) use amongst prostate cancer survivors receiving androgen‐deprivation therapy (ADT), and downstream implications for osteoporosis and fracture diagnoses, as well as pharmacological osteoporosis treatment in a national integrated delivery system.

Potential Savings in Medicare Part D for Common Urological Conditions

Introduction: Millions of patients take prescription medications each year for common urological conditions. Generic and brand‐name drugs have widely divergent pricing despite similar therapeutic benefit and side effect profiles. We examined prescribing patterns across provider types for generic and brand‐name drugs used to treat 3 common urological conditions, and estimated economic implications for Medicare Part D spending. Methods: We extracted 2014 prescription claims and payments from Medicare Part D and categorized oral medications used to treat 3 urological conditions, namely benign prostatic hyperplasia, erectile dysfunction and overactive bladder. We examined claims and payments for each medication among urologists and nonurologists. Lastly, we estimated potential savings by selecting a low cost or generic drug as a cost comparator for each class. Results: There were significant differences in prescribing patterns across these conditions, with urologists prescribing more brand‐name and expensive medications (p <0.001). The total potential savings related to prescriptions of more expensive and nongeneric drugs in 2014 was

Early National Dissemination of Abiraterone and Enzalutamide for Advanced Prostate Cancer in Medicare Part D

1 billion (benign prostatic hyperplasia

Limitations of Prostate-specific Antigen Testing After a Prostate Cancer Diagnosis.

348,454,910, erectile dysfunction

Cardiovascular and metabolic toxicity of abiraterone in castration-resistant prostate cancer: Post-marketing experience.

10,211,914 and overactive bladder

Treating Advanced Prostate Cancer—the Human Factor

698,130,833). These potential savings comprised 53% of the total spending for these medications in 2014. Conclusions: Within Medicare Part D the potential savings associated with generic substitution for higher cost and nongeneric drugs for 3 common urological conditions surpassed