June 10, 2014
MD Anderson discoveries presented at ASCO meeting
BY MD Anderson staff
Findings presented at the American Society of Clinical Oncology’s recent annual meeting offer new hope for preserving fertility in a select group of young women with early-stage breast cancer.
An international study found that hormone receptor-negative breast cancer patients who received the drug goserlin in addition to standard chemotherapy were 64% less likely to develop premature ovarian failure — a common side effect of chemotherapy — compared to women who received chemotherapy alone. They also were more likely to have successful pregnancies. In addition, those receiving goserlin were 50 percent more likely to be alive four years after treatment, compared to those who received chemotherapy alone.
Goserelin is a hormone-suppressing agent that works by temporarily shutting down ovarian function, putting the patient into a postmenopausal state. The drug is widely used to control ovulation timing in infertility procedures. It’s also approved as a hormonal therapy in advanced breast and prostate cancers.
For the study, 257 premenopausal women with early-stage hormone receptor-negative breast cancer were randomized to receive cyclophosphamide-based chemotherapy alone, or chemotherapy plus goserelin. Goserelin was given monthly, with injections beginning one week before the first dose of chemotherapy.
The Phase III study was conducted at sites around the world, including MD Anderson. Sharon Giordano, M.D., chair of Health Services Research, was the study’s discussant and spoke to the Associated Press about the results:
“The findings are quite provocative,” said one independent expert, Dr. Sharon Giordano, a breast cancer specialist at the University of Texas MD Anderson Cancer Center in Houston. “Using goserelin is an option I would discuss with selected patients” but it doesn't guarantee fertility preservation.
Giordano went on to say that women may want to consider other fertility options, including creating and freezing embryos post-treatment.
— Laura Sussman
New combination therapy benefits metastatic colon cancer patients
In an aggressive disease known for poor response rates, researchers from MD Anderson Cancer Center found that patients with advanced colorectal cancer responded well to a combination of the drugs vermurafenib, cetuximab and irinotecan.
The Phase I trial, presented in a poster discussion at the American Society of Clinical Oncology’s 2014 Annual Meeting in Chicago, examines a specific mutation in the BRAF gene, which is present in 5 to 10% of colorectal cancer patients.
Previous research identified this mutation as a target for therapy, but response rates to vemurafenib alone were poor, leading researchers to inquire about combining it with different drugs.
“Patients with a BRAF mutation in colorectal cancer are recognized for having aggressive disease that doesn’t typically respond to standard chemotherapy,” said David Hong, M.D., associate professor in Investigational Cancer Therapeutics and lead author. “So when BRAF inhibitors initially started, there was excitement this could become the new standard of care; however, we found they didn’t work very well.”
In the trial, researchers combined escalating doses of vermurafenib (V), along with cetuximab (C) and irinotecan (I), two drugs previously used in the treatment of metastatic colorectal cancer. Twelve patients were enrolled at two dose levels, including seven at dose level one (V-480 mg, C-250 mg and I-180 mg) and five at dose level two with vemurafenib increased to 720 mg.
Radiographic images were evaluated every four cycles over the course of a 14-day cycle of treatment. Patients were assessed for adverse events, with the most common being rash, diarrhea and nausea.
Results show improved responses
Of the nine evaluable patients, partial responses or stable disease was seen in all eight patients with colorectal cancer who underwent restaging scans following the beginning of their treatment. The response rate for the eight colorectal patients was 50%, whereas response rates with single agent vemurafenib were less than 10%.
“What’s promising is the fact that we’re seeing these high response rates in early studies, which suggests this could become a new standard of care down the line,” Hong said. “There’s clearly some kind of synergistic activity with the combination.”
A U.S. cooperative randomized Phase II trial of this combination in BRAF-mutated colorectal cancer will begin later this summer, and led by Scott Kopetz, M.D., Ph.D., assistant professor in Gastrointestinal Medical Oncology, the senior author on the Phase I study.
“While early, the exciting aspect is that we’re seeing substantial response rates. But questions remain about
the duration of these responses and what the mechanisms of resistance are,” Kopetz said. “By expanding on our initial findings and moving to the cooperative group network we’ll be able to rapidly perform studies that could lead to getting this combination approved.”
Hong, Kopetz and Funda Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics, receive research support from Genentech. Overman receives research support from Genentech and Roche.
In addition to Hong and Kopetz, other authors on the MD Anderson study are Michael Overman, M.D., Van Morris, M.D., Brian Kee, M.D., Sarina Piha-Paul, M.D., Ralph Zinner, M.D., David Fogelman, M.D., Imad Shureiqi, M.D., and Funda Meric-Bernstam, M.D.
— Will Fitzgerald
Less bisphosphonates may not compromise care
Women with metastatic breast cancer to the bone may be able to receive bisphosphonates, the bone-targeting class of drugs like zoledronic acid, less often after the first year of monthly administration. With that practice change, they may also reduce their risk of serious side effects, according to a study led by researchers at MD Anderson Cancer Center.
The research was presented at the American Society of Clinical Oncology 2014 Annual Meeting by MD Anderson’s Gabriel Hortobagyi, M.D., professor in Breast Medical Oncology. The study found that receiving zoledronic acid every 12 weeks after one year of monthly administration was as efficacious as continuing to receive it monthly.
Findings from the OPTIMIZE-2 study could have an impact not just in the setting of metastatic breast cancer, but other solid tumors, as well as multiple myeloma, where monthly intravenous bisphosphonates are used to prevent skeletal-related events and the loss of bone mass.
According to the American Cancer Society, 232,670 women will be diagnosed with breast cancer in 2014 and 40,000 will die from the disease. The overwhelming majority of metastatic breast cancer patients will develop a bone metastasis at some point during their care, said Hortobagyi.
MD Anderson has a long history of research discoveries with bisphosphonates. In the 1990s, Hortobagyi and Richard Theriault, D.O., authored the practice-changing publications in metastatic breast cancer showing pamidronate’s association with fewer skeletal-related events (SRE) — including bone fractures and bone pain, and spinal cord compression — leading to the incorporation of the drug class into the metastatic disease management.
“With those findings, it became standard of care to continue bisphosphonates for the life of the metastatic breast cancer patient. Yet there were no definitive studies or guidelines confirming this clinical practice or looking at long-term side effects,” said Hortobagyi, the study’s national principal investigator.
“The OPTIMIZE-2 trial is the largest study designed to date looking at the frequency of bisphosphonate delivery. The study determined that giving the therapy less often after a year of earlier treatment was non-inferior than receiving the therapy monthly, and we found that less frequency is likely associated with a reduced toxicity,” he explained.
The Phase III prospective, double-blind study enrolled 403 metastatic breast cancer patients, with MD Anderson enrolling more patients than any other site. All had previously received nine or more doses of bisphosphonates in their first 10-15 months of therapy. Patients were randomized (1:1) to receive an additional year of 4 mg IV of zoledronic acid, either every month (Q4 wk) or every three months (Q12 wk) for an additional year. Median age was 59 years old, and baseline disease characteristics were similar in both arms. The study’s primary endpoint was the number of participants with no more than one SRE. Primary analysis was non-inferiority, with a pre-defined margin of 10%.
The researchers found that the SRE rate was comparable in both groups of patients — 22% in the monthly arm, and 23.2% in the every-three-month arm — indicating less treatment wasn’t inferior. The researchers also found similar overall safety profiles in both arms. However, more kidney-related adverse events were reported in the monthly arm — 9.6%, compared to 7.9 % in the every-three-month arm. Two patients in the monthly arm developed osteonecrosis of the jaw.
The research lets both patients and physicians know that in this case, less may be better than more; a lesson that may extend beyond these findings, said Hortobagyi.
“In general in breast cancer, we’re getting to the point where our patients are doing well enough that we can begin to start reducing the treatments they receive, as we’re likely over-treating the majority of our patients — and this study is an example of that,” said Hortobagyi.
Hortobagyi noted that the study is not without limitations. It focused on patients for one year post-initial bisphosphonates treatment, whereas many patients receive bisphosphonates for the length of their treatment for metastatic disease, even if they develop an SRE.
In addition to Hortobagyi, authors on the study include: Allan Lipton, M.D., Penn State Hershey Medical Center; Helen Chew, M.D., University of California-Davis; William J. Gradishar, M.D., Northwestern University Feinberg School of Medicine; Ming Zheng, Ph.D., Novartis Pharmaceuticals Corporation; and Catherine Van Poznak, M.D., University of Michigan.
Novartis supported the trial with funding; Hortobagyi served as member and chair of the OPTIMIZE-2 Steering Committee and was compensated for that activity.
— Laura Sussman
Long-used chemo drug extends survival for prostate cancer patients
Using a decades-old chemotherapy drug in combination with standard hormone therapy can extend the lives of men with metastatic prostate cancer by more than a year, according to research presented at the recent meeting of the American Society of Clinical Oncology in Chicago.
A study showed those given the chemo drug docetaxel lived nearly 58 months, compared to 44 months for those who weren't.
“This is the first study to identify a strategy that prolongs survival in newly diagnosed metastatic prostate cancer,” said Christopher Sweeney, M.B.B.S, an oncologist at Dana Farber Cancer Institute and the study’s lead author. “The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy.”
More than 230,000 new cases of prostate cancer are diagnosed each year in the U.S., and the disease kills close to 30,000 here annually. It’s the most common cancer in men.
Androgen deprivation therapy (ADT) is the standard initial treatment for prostate cancer, which is fueled by the hormone. Docetaxel is used only after the disease develops a resistance to the therapy and continues to grow. The 790 men with newly diagnosed metastatic prostate cancer enrolled in the study were treated with ADT alone or ADT and docetaxel combined.
In an interview with the Houston Chronicle, Christopher Logothetis, M.D., chair of Genitourinary Medical Oncology at MD Anderson, agreed the findings were “practice changing,” but pointed out the Phase III study didn't benefit every patient.
“This (addition of chemotherapy) is not for all patients,” said Logothetis, director of the David H. Koch Center for Applied Research of Genitourinary Cancers. “The challenge will be for doctors to resist the temptation to broaden the chemotherapy pool to everyone because of the study. Patients should get to experienced doctors who know how to tailor treatment to the individual.”
At a 29-month follow-up, there were 136 deaths among the ADT-alone group, compared to 101 in the group that received combination therapy. At that time, patients whose cancer had metastasized to other organs and/or spread to their bones showed the most relative improvement, living 17 months longer if treated with the combination.
The study, which was funded by the National Cancer Institute, showed docetaxel delayed progression of the cancer as well.