ASCO 2015 Highlights – Drug and Device Digest

ASCO  ASCO Annual Mtg

The 51st ASCO Annual Meeting took place in Chicago May 29 – June 2, brought together more than 30,000 oncology professionals from a broad range of specialties from around the world. This year’s Annual Meeting was focused on the theme of Innovation and Illumination, pointing to the potential for integrating cancer science and health information technology to achieve more rapid improvements in patient care. Along with new research,

ASCO President Peter Yu, MD stated at the meeting, “We are in an information age and there is a lot of data coming at us. We need to become smarter and more nimble about how we look at data and derive knowledge, and then that drives actual decision-making that improves patient outcomes.”

Prostate Cancer Foundation’s a few highlights for patients

Upfront Therapy with Docetaxel Prolongs Overall Survival in Men with Hormone-Naïve Metastatic Prostate Cancer Commencing Androgen Deprivation Therapy: First survival results from STAMPEDE: Dr. Nicholas James, University of Warwick and Queen Elizabeth Hospital Birmingham.

Dr. Nicholas James presented the first survival results released from the STAMPEDE clinical trial, which tested the outcome of adding various therapies to standard of care (SOC) consisting of androgen deprivation therapy (ADT) with or without radiotherapy (RT), in hormone-naïve patients either presenting with metastatic disease or relapsing after prostatectomy or RT. Results were presented from four randomized study arms: SOC (1184 patients), SOC + zoledronicacid (593 patients), SOC + docetaxel + prednisolone (592 patients), and SOC + zoledronicacid + docetaxel + prednisolone (593 patients). No benefits to failure free survival (FFS) or overall survival (OS) were observed with addition of zoledronicacid, a bisphosphonate that reduces bone fractures and pain from bone metastases. The addition of docetaxel + prednisolone to SOC extended median FFS from 21 months to 37 months and extended median OS from 67 months to 77 months. These results supported previous results from the CHAARTED trial where a median overall survival (OS) improvement from 44 to 57.6 months with the addition of docetaxel to ADT in hormone-sensitive metastatic prostate cancer patients was observed. Collectively, these results supported a paradigm change in clinical practice. Docetaxel in combination with ADT should now be considered much earlier in the treatment regimen for men with hormone-naïve metastatic prostate cancer.

Neoadjuvant Chemotherapy Combined with ADT and IMRT Shows Survival Benefit in Localized High-Risk Prostate Cancer Patients: Results from RTOG 0521. Dr. Howard Sandler, Cedars-Sinai Medical Center

Dr. Howard Sandler presented results from RTOG 0521, a Phase III trial testing the addition of docetaxel + prednisone to ADT+ Intensity-Modulated RT (IMRT) in treatment-naïve high-risk localized prostate cancer. At a median of 6 years of follow up, 563 patients were evaluable. The addition of docetaxel + prednisone to ADT + IMRT improved the 4-year overall survival (OS) rate from 89% to 93% of patients and improved 6-year disease-free survival rates from 55 to 65%. These studies indicated that neoadjuvant chemotherapy in combination with ADT and IMRT may benefit patients with localized high-risk prostate cancer and should be considered as the first line of therapy. These studies indicate that neoadjuvant chemotherapy in combination with ADT and IMRT may benefit patients with localized high-risk prostate cancer and should be considered as the first line of therapy.

Genomic Analysis of Circulating Cell-free DNA Identifies Mechanisms of Primary and Acquired Resistance to Enzalutamide in Metastatic Castration-Resistant Prostate Cancer (mCRPC). Dr. Arun Azad, BC Cancer Agency, Vancouver, Canada

Dr. Arun Azad (BC Cancer Agency, Vancouver, Canada) and colleagues assessed genomic alterations in cfDNAfrom metastatic castrate resistant prostate cancer (mCRPC) patients prior to and following the development of resistance to treatment with enzalutamide.Poorer median progression-free survival (mPFS) in response to enzalutamide was associated with pre-existing copy-number amplifications of the oncogenes AR, MYC and MET, mutations in AR, or copy-number losses of the tumor-suppressor gene RB1. Ten of 44 patients acquired new copy-number changes during enzalutamide treatment. Acquired AR or MYC amplifications or RB1-loss were associated with poorer mPFSduring treatment with enzalutamide. Five patients acquired new AR mutations during enzalutamide treatment and also had significantly reduced mPFS. Ongoing studies are assessing tumor genomic alterations in patients enrolled in clinical trials with other therapies. These studies will lead to the establishment of Precision Medicine treatment models, in which tumor genomic profiles are used to select treatments most likely to provide benefit and avoid treatments for which benefit is unlikely.

Statin Use at the Time of Initiation of Androgen Deprivation Therapy Delays Time to Progression in Patients with Hormone-Sensitive Prostate Cancer. Dr. Lauren Harshman, Dana-Farber Cancer Institute, Harvard Medical School.

Dr. Lauren Harshman and colleagues hypothesized that the use of statins may boost the efficacy of androgen deprivation therapy (ADT) by competing with DHEAS for SLCO2B1 uptake and thereby further limiting the amount of androgens available to fuel prostate cancer cells. In a retrospective analysis of 926 analyzable patients who initiated ADT between 1996 and 2013, statin use at the time of ADT initiation was associated with a significantly increased median time to progression on ADT (27.5 months for statin users vs. 17.4 months for non-statin users). These differences were observed regardless of whether patients had radiographic evidence of metastasis or only biochemical relapse at the time of ADT initiation. These results require validation in a prospective study and further studies are needed to definitively define the mechanisms involved. Nevertheless, statins have an established safety profile and may be an effective anti-cancer therapeutic in combination with ADT

Other Hightights

The Saturday, May 30, Education Session of “Introduction to Methods in Comparative Effectiveness Research,” chaired by Sharon H. Giordano, MD, MPH, of The University of Texas MD Anderson Cancer Center, provided an overview of a variety of approaches to comparative effectiveness research (CER).

“A lot more people are starting to conduct research in this area,” Dr. Giordano said. “There has been a general realization that, although it would be ideal to do a randomized clinical trial for every situation in every population, it is not realistic, and because of those gaps in knowledge, people are interested in using comparative effectiveness research to help determine the best way to treat their patients. The purpose of CER is to assist consumers, clinicians, purchasers, and policy makers to make informed decisions that will improve health care at both the individual and population levels.”

Natasha K. Stout, PhD, of Harvard Medical School and Harvard Pilgrim Health Care Institute, discussed the use of disease simulation modeling in CER. Disease simulation modeling is an Institute of Medicine -endorsed methodology that helps to fill evidence gaps left by clinical trials or observation studies. According to Dr. Stout, models can often be used in cases in which a decision needs to be made immediately but for which traditional research would take years to produce an outcome of interest. Modeling can project both near- and long-term outcomes in a timely manner, and, in some cases, can project the value of conducting more research in a given area.

PK poster presentation:

PK of the chimeric anti-GD2 (ch14.18) antibody in children with high-risk neuroblastoma: Children’s Hospital of Philadelphia, PA and United Therapeutic Corp,, RTP, NC

Ch14.18 is a Chimeric Monoclonal Antibody (cMoAb), improves survival in high-risk neuroblastoma according previously reported study. Ch14.18 disposition was highly variable in children. Infusion dose was of 25 mg/m2 over 10 h to male (n-6) and female (n=4) children of 1 to 7 yr old. Mean Cmax, half-life (HL) clearance (CL) and volume distribution (Vd) were 14 mcg/mL, 260 hr, 11 mL/h/m2 and 2.8 L/m2, respectively. C14.18 CL, Vd and HL in children were similar to those in adults at same dose level.


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