News from ASCO: Prostate and Colorectal Cancers

Prostate Cancer Research Produces Two New Therapies

Prostate cancer has seen its share of progress over the past few years, including several new drugs that have been approved for patients with metastatic disease. Two clinical studies were announced at ASCO’s Genitourinary Cancers Symposium in early February that foreshadow additional therapies that will help further extend survival and improve quality of life.

Alpharadin (radium-223) uses alpha particles, a type of ionizing radiation that penetrates only a few layers of cells and avoids injury to nearby tissue, to kill cancer cells that have spread to the bone, while MDV3100 works by preventing the tumor cells from using testosterone that can spur cancer growth.

The Alpharadin trial included 922 patients with castration-resistant prostate cancer (CRPC) with bone metastases who had previously received Taxotere (docetaxel), were Taxotere ineligible or had refused Taxotere. The patients were randomized to Alpharadin or placebo, with all patients receiving best supportive care. It prolonged survival by 25 percent (14 months versus 11.2 months) and delayed the time to a patient’s first skeletal-related event, such as spinal cord compression or bone fracture, from 8.4 months to 13.6 months. Side effects were minimal and included neutropenia and diarrhea.

The MDV3100 trial included 1,199 patients with advanced CRPC who had progressed after treatment with Taxotere and hormone therapy. The drug increased survival by 35 percent over placebo (18.4 months versus 13.6 months), lowered PSA levels and delayed cancer growth by an average of five months. Side effects included diarrhea, fatigue and hot flashes.

Nicholas Vogelzang, MD, chairman and medical director of the Developmental Therapeutics Committee of the US Oncology Network, a division of McKesson Specialty Health, calls the results unprecedented. “This is going to definitely change the way we take care of patients every day in the office.”

IMRT Edges Out Proton Beam Therapy for Prostate Cancer

A study examining three types of radiation therapy in early-stage prostate cancer found the standard of treatment is better than a more expensive, newer form of radiation using proton beams instead of X-rays. Researchers examined data from more than 12,000 Medicare patients with early-stage prostate cancer who were treated with one of three forms of radiation: intensity-modulated radiation therapy (IMRT), conformal radiation therapy (CRT, an older form of radiation) or proton-beam therapy. Patients who received IMRT had fewer occurrences of bowel problems and hip fractures than CRT. While CRT costs the least, it was associated with a higher rate of recurrence. Patients who received proton-beam therapy, which is the most costly of the three, had a higher rate of gastrointestinal side effects but a recurrence risk similar to patients who received IMRT.

Brachytherapy Better Than Surgery and External-Beam Radiation, Yet Least Used

In a study comparing prostate cancer treatments, researchers compared prostatectomy, external-beam radiation therapy (EBRT) and brachytherapy, a form of radiation where radioactive wires or seeds are implanted near the prostate tumor. More than 130,000 patient records were reviewed for cost, toxicity and further treatment for side effects. After a median of more than five years, the study found that brachytherapy had the lowest cost per patient-year. EBRT was found to be the most expensive per patient-year and the most toxic, with gastrointestinal problems and bladder bleeding. Although brachytherapy came out on top, it’s the least utilized treatment of the three, with only 12 percent of the patient population studied undergoing brachytherapy.

The American Society of Clinical Oncology (ASCO) hosted annual symposia in January and February that brought together thousands of cancer researchers, oncologists, industry professionals, advocates and survivors to report on advances in genitourinary (GU) and gastrointestinal (GI) cancers.

Exercise Affects Gene Expression and Prostate Cancer Mortality

When researchers found that men who exercised after a prostate cancer diagnosis fared better, the next step was to learn why.

Past research showed that patients who exercised at least three hours a week lowered their risk of death by about half, and reduced the risk of death specifically from prostate cancer by 61 percent.

In a new study, researchers from the University of California, San Francisco and Duke University examined 70 men with earlystage, low-risk prostate cancer who were under watchful waiting instead of active treatment. Patients were grouped into two categories: those who exercised vigorously at least three hours a week and those who did not. Exercises included jogging, tennis and swimming laps.

After looking at changes in gene expression and pathways between the two groups, researchers found 184 genes were different, including those that are involved in tumor suppression.

“This was a small study with provocative findings that should be interpreted cautiously and warrant confirmation in a larger study,” says June Chan, ScD, the study’s senior author. “These preliminary data suggest that DNA repair in the prostate gland is one mechanism through which vigorous physical activity may protect against prostate cancer progression, and there are potentially more.”

The next steps include a larger study of men on watchful waiting and an examination of the effects of exercise in men after a cancer recurrence. In the future, this information could be used to predict, monitor and prevent prostate cancer progression.

New Drug Successful in Advanced Colorectal Cancer

Patients with advanced colorectal cancer appear to do better when treated with a new type of multi-targeted therapy called regorafenib. The phase 3 trial, called CORRECT, showed that regorafenib improved survival by a median of 1.4 months, increasing the survival rate from 5 months with placebo to 6.4 months. Although it represents a small bump in median survival, it’s a 29 percent increase in overall survival in a hard-to-treat patient population.

“This is one of those things that I hope we can educate people about, that it implies that every patient lives a month longer. That’s not true,” says Axel Grothey, MD, of the Mayo Clinic in Rochester, Minn., and lead author of the trial who presented the results at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium in San Francisco on Jan. 21. “Some patients don’t benefit at all. One patient lived almost a year.” Researchers typically look at the median number, not the average, when analyzing study results. The median is the middle number of a rather large range.

Jason Faris, MD, a medical oncologist who specializes in gastrointestinal cancers at Massachusetts General Hospital Cancer Center, says the fact that the drug demonstrated a statistically significant benefit in survival is exciting. “This excitement must, of course, be weighed against the magnitude of the absolute gain in overall survival that those patients experienced compared to placebo-treated patients, which was only 1.4 months. Nonetheless, demonstrating an overall survival benefit in a population who largely—more than 80 percent— have been exposed to three or more prior regimens is impressive.”

The trial randomized 760 patients, with two-thirds receiving regorafenib, a third of patients receiving placebo, and both receiving best supportive care. The drug stabilized the disease in nearly half of patients, delaying or reducing tumor growth in 44.8 percent of patients as opposed to 15.3 percent in the placebo arm. This shows the drug may have a future as a maintenance therapy, Grothey says. Common side effects reported included hand-foot rash, fatigue and diarrhea.

The next step will be to examine quality-of-life aspects and determine patient and tumor characteristics that may help predict which patients would benefit from the drug. Biomarker analysis results are expected this summer. Bayer, the drug’s maker, is working on an early access study, which would allow patients to receive the drug while also monitoring its side effects further.