Immunotherapy, genomic profiling, and investigating game-changing drug therapies topped the list of most important cancer research and clinical developments at Dana-Farber Cancer Institute in 2014.
Some highlights include:
Some of the most dramatic evidence to date of the potential of immunotherapies was uncovered by Dana-Farber researchers and others this year concerning Hodgkin lymphoma.
In an early-phase clinical trial, research showed nivolumab, a drug that unleashes the immune system to attack cancer cells, achieved complete or partial remissions in Hodgkin lymphoma patients with resistant forms of the disease.
The success of nivolumab in this study prompted the U.S. Food and Drug Administration (FDA) to designate it a "breakthrough therapy" for treating relapsed Hodgkin lymphoma, and a large, multinational Phase 2 trial is now under way.
"What makes these results especially encouraging is that they were achieved in patients who had exhausted other treatment options," said the study's co-senior author, Margaret Shipp, MD, chief, Division of Hematologic Neoplasia at Dana-Farber. "We're also excited by the duration of responses to the drug: the majority of patients who had a response are still doing well more than a year after their treatment."
The study was published in the New England Journal of Medicine and simultaneously presented at the annual meeting of the American Society of Hematology (ASH) in San Francisco.
Research results by Dana-Farber investigators showed a combination drug therapy may be highly effective in recurrent ovarian cancer. This is the first ovarian cancer study to test a combination of drugs that could be taken orally.
A clinical trial compared the activity of the combination of the drug olaparib, which blocks DNA repair, and the blood vessel inhibitor drug cediranib, against olaparib by itself. Trial results showed a near doubling of progression-free survival benefit for the combination therapy over use of the single drug alone.
"The findings of this study are exciting because they support the idea that combining these two targeted oral therapies results in significant activity in ovarian cancer, more so than olaparib alone," said Joyce Liu, MD, MPH, the lead investigator and medical oncologist at the Susan F. Smith Center for Women's Cancers at Dana-Farber. "We are looking forward to further exploring this combination in ovarian cancer and potentially increasing effective treatment options for our patients with this cancer."
The study results were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) meeting in Chicago.
Based on results of a clinical trial led by Dana-Farber scientists, in 2014 the FDA approved a molecularly targeted drug as second-line treatment in advanced stomach cancer that has progressed after standard chemotherapy has failed.
"For years we have looked for new and really effective drugs for stomach cancer," said Charles Fuchs, MD, MPH, director of the Gastrointestinal Cancer Center at Dana-Farber. "We have relied on standard chemotherapies for a long time, and we've needed targeted agents based on the fundamental biology of stomach cancer."
The drug is called Ramucirumab. It is a monoclonal antibody compound that attacks the cancer by preventing it from developing new blood vessels to nourish its growth. Such drugs are known as anti-angiogenesis agents. Ramucirumab molecules latch onto the vascular endothelial growth factor (VEGF) receptor-2 on blood vessel cells, blocking them from receiving signals the cancer cells send in an effort to recruit new blood vessels. Anti-angiogenic treatments can shrink tumors by depriving them of oxygen and other nutrients.
Dramatic results in a multi-center phase 3 trial reported this year should change the way physicians have routinely treated prostate cancer patients for decades.
The study, which was led by scientists at Dana-Farber, showed men with newly diagnosed metastatic, hormone-sensitive prostate cancer lived more than a year longer when they received a chemotherapy drug as initial treatment instead of waiting to for the disease to become resistant to hormone blockers.
"The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy," said Christopher J. Sweeney, MBBS, of Dana-Farber's Lank Center for Genitourinary Oncology and principal investigator for the study.
He presented the results of the trial at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
This year, scientists at Dana-Farber and Brigham and Women's Hospital continued to build the massive cancer genome research project called Profile. The project is generating one of the world's largest databases of genetic abnormalities known to be involved in cancer. It is a resource that will make possible a wealth of studies on the genetic roots of the disease. Every patient at Dana-Farber/Brigham and Women's Cancer Center, and now pediatric cancer patients treated at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, is offered the opportunity to participate in the study.
For each participating patient, Profile scientists are analyzing DNA samples of their cancers, using a new "next-generation" sequencing technology that scans more than 300 cancer-related genes for mutations and other DNA alterations. From the results of these scans, pathologists can determine the particular set of abnormalities that are driving the cancer: a personalized tumor profile.
"The power of Profile lies in the sheer volume of the data it is amassing on the genetics of cancer, and the potential to correlate distinctive DNA abnormalities in a specific person's cancer with its behavior and how it responds to treatment," explained Barrett Rollins, MD, PhD, Dana-Farber's chief scientific officer.
Researchers at Dana-Farber recently developed, and are currently testing, agents that target Epidermal Growth Factor Receptor (EGFR) mutations when current drugs lose their effectiveness. The year marked the 10th anniversary of when researchers at Dana-Farber published a study showing that lung cancer patients whose tumors had a malfunctioning version of EGFR responded dramatically to a drug that specifically targets the EGFR protein. The findings launched the era of precision medicine for lung cancer, transforming the way the disease is treated in many patients.
"Prior to this research, lung cancer treatment had not made much progress for more than a decade," says Bruce Johnson, MD, chief clinical research officer at Dana-Farber, who co-led the 2004 study with colleagues Pasi Jänne, MD, PhD, Matthew Meyerson, MD, PhD, and William Sellers, MD (now of the Novartis Institutes for BioMedical Research). "For the 20 to 40 percent of patients with advanced lung cancer who responded to chemotherapy, remissions usually lasted four to six months, and average survival rates were about a year. Today, patients with EGFR mutations who are treated with targeted drugs have a year of remission and survive an average of two to three years, with some making it to five years or more."
Dana-Farber Cancer Institute