As preparations for ASCO’s annual meeting heat up, a pre-meeting Presscast highlighted four abstracts of special interest to be presented in greater detail at the meeting in Chicago. All four are based on data from Phase III trials:
- In the ELOQUENT-2 trial, a new monoclonal antibody — elotuzumab — extended remission when added to standard therapy for relapsed/refractory multiple myeloma
- A phase 3 double-blind randomized trial showed that daily use of a vitamin B3 pill (nicotinamide) reduces incidence of new non-melanoma skin cancers (basal cell and squamous cell cancers), as well as pre-cancerous actinic keratoses in people at high risk for skin cancer
- Data from two Phase III Children’s Oncology Group Studies show that a specific genetic abnormality enables more intensive therapy to be given to children with Wilms Tumor, thereby improving outcomes in this high-risk group
- Results from STAMPEDE show that docetaxel — but not zoledronic acid — extended overall survival when given with hormone therapy to men with newly diagnosed, metastatic, hormone-naive prostate cancer
“Trials like these are engines of progress for people with cancer of all ages. In just four studies, we see the potential to spare thousands of people the stress and complications of a new cancer diagnosis, and to extend the lives of children and adults facing cancer in its most daunting forms. At ASCO’s meeting in Chicago, we’ll continue to see the transformative power of investments in cancer research and care,” stated ASCO President Peter Paul Yu, MD, FACP, FASCO, in an official press release.
Elotuzumab in Multiple Myeloma
Interim results of a Phase III trial show that adding the monoclonal antibody elotuzumab to standard therapy with lenalidomide/dexamethasone reduced the risk of cancer progression and death by 30% in patients with relapsed/refractory multiple myeloma.
“This therapy combines the precision of a targeted, immune-based therapy with traditional myeloma therapy. The results are very encouraging, giving renewed hope to patients who have relapsed,” stated ASCO President-Elect Julie M. Vose, MD, who was not involved in this trial.
“Elotuzumab acts on the tumor cell and enhances the activity of natural killer cells, providing a sort of ‘double whammy’,” said lead author Sagar Lonial, MD, Winship Cancer Institute of Emory University School of Medicine, Atlanta, GA. “We are excited about the progression-free survival results attributable to this novel first-in-class antibody.”
This is the largest study of a targeted monoclonal antibody in multiple myeloma and the first Phase III study to show the benefit of this approach in multiple myeloma. The study randomized 646 patients with relapsed/refractory multiple myeloma to standard therapy with lenalidomide/dexamethasone or standard therapy plus elotuzumab. At a median follow-up of 24 months, progression-free survival (PFS) was 41% in the triple therapy arm versus 27% in the standard therapy arm (P=.0004).
“It is striking that these curves remain separated at 2 years, which speaks to the power of an immune approach as part of treatment of multiple myeloma,” Dr. Lonial commented.
Importantly, patients at high risk due to genetic abnormalities — del(19p) and t(4;14) — had similar benefit from elotuzumab as in the overall study. These patients typically have less benefit from conventional therapies, Dr. Lonial said.
Overall elotuzumab was well tolerated with no significant increases in adverse events. About 10% of patients experienced a mild infusion reaction with the first few doses of the monoclonal antibody. Elotuzumab has been granted a Breakthrough Designation by the U.S. FDA.
Vitamin B3 Supplement (Nicotinamide) and Skin Cancer
An oral form of vitamin B3 (nicotinamide) taken twice daily for 12 months reduced the rate of new skin cancers by 23% compared to placebo in people at high risk for these cancers. This simple, inexpensive pill is safe, affordable, and available over the counter, making it widely available for people at risk.
“When we stopped treatment, there was no difference between the two arms, suggesting that continuous treatment is needed. I should emphasize that these results pertain to high-risk patients who have had other skin cancers, not the general public,” said lead author Diona Damian, MBBS, PhD, Dermatology University of Sydney, Australia.
“The pill does not take the place of sunscreen use and regular skin check-ups for people at high risk,” she emphasized.
The study included 386 patients who had at least two non-melanoma skin cancers over the past 5 years and were therefore deemed high risk. Patients were randomized to daily nicotinamide or placebo for 12 months. Dr. Damian said the patient mix reflected those seen in a typical skin cancer clinic. Average age was 66 years and two thirds were men, many with ongoing chronic comorbidities.
Nicotinamide reduced the rates of new basal cell cancer and squamous cell cancer diagnoses by 23% compared with placebo. Nicotinamide reduced the rates of actinic keratoses (pre-cancers) by 11% at 3 months and by 20% at 9 months of treatment compared with placebo.
This preventive treatment has no side effects, Dr. Damian said.
High-Risk Wilms Tumor
Intensifying therapy for children with Wilms Tumor improves outcome in patients with a chromosomal abnormality associated with poorer prognosis, according to results of two Phase III trials conducted by the Children’s Oncology Group.
Previous studies of patients with the genetic abnormality treated with conventional regimens showed 4-year relapse-free survival rates of 74.9% for stage I/II disease and 65.9% for stage III/IV disease. Intensified, or augmented therapy, increased the rates to 83.9% and 91.5%, respectively.
“Augmentation of therapy for favorable histology Wilms Tumor with LOH improves outcomes, particularly for stage III/IV disease. We are encouraged that augmentation can overcome a known adverse biomarker,” said lead author David B. Dix, MD, British Columbia Children’s Hospital, Vancouver, Canada.
The AREN0533 and ARENO532 studies evaluated whether augmenting therapy would improve event-free survival for patients with favorable Wilms histology and the genetic abnormality (tumor-specific loss of heterozygosity [LOH] of chromosomes 1p and 16q). Augmentation strategies were as follows:
At a median follow-up of 3.6 years, of a total of 1134 patients, 35 stage I/II patients and 52 stage III/IV patients had combined LOH 1p and 16q; these patients formed the basis of the analysis. Grade 3 or higher hematologic toxicity was the most common adverse event observed with the augmented regimen given to stage III/IV patients, occurring in 60%. The analysis did not establish superiority of either augmented regimen.
LOH 1p, 16q testing is considered the standard of care at the Children’s Oncology Group Biopathology Center and several other centers, Dr. Dix noted.
Docetaxel for Hormone-Naive Advanced Prostate Cancer
The STAMPEDE trial found that the addition of docetaxel to standard hormone therapy improved overall survival (OS) by a median of 10 months in men with newly diagnosed advanced prostate cancer who were previously naive to hormone therapy; however, the addition of zoledronic acid to standard therapy had no effect on survival in this group of men and the combination of docetaxel plus zoledronic acid was not superior to docetaxel alone.
“Docetaxel chemotherapy should be routine in men with newly diagnosed metastatic prostate cancer about to start hormones for the first time. There is some uncertainty regarding the survival benefit in men with non-metastatic prostate cancer, but docetaxel should be offered upfront to these men to prolong failure free survival,” said lead author Nicholas David James, MD, PhD, University of Warwick in Coventry, U.K. ” It’s clear that zoledronic acid does not benefit these patients and should not be offered as upfront treatment for advanced prostate cancer.”
STAMPEDE is the largest randomized clinical trial conducted to date of treatment for prostate cancer, including more than 6500 men enrolled since 2005. The innovative, ongoing, multi-arm study has an adaptive trial design, modifying the standard of care (SOC) control, arm as new patients are continuously enrolled. Ineffective treatments are dropped and new arms are added to assess the efficacy of newer treatments. The control, or standard of care (SOC) arm, has evolved over time.
Results to be presented at ASCO 2015 focus on 2962 hormone-naive men assigned to one of 4 of STAMPEDE’S 9 different treatment arms: SOC, SOC with docetaxel for 6 cycles, SOC with zoledronic acid for 2 years, and SOC with both docetaxel and zoledronic acid.
By Don Sharpe