Two new drugs show promise for patients with aggressive breast cancer

August 12, 2016

Patients with aggressive subtypes of locally-advanced breast cancer may have new treatment options on the horizon, according to two reports published in July in the New England Journal of Medicine. Results of two different investigational arms of a multi-drug phase II trial conducted in part by researchers at the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, show that use of new targeted therapies neratinib or a combination of veliparib and carboplatin improves outcomes, when used in addition to standard chemotherapy before surgery for patients with HER2-positive and triple-negative breast cancer, respectively. The results are part of the multi-institutional I-SPY 2 study.

"Compared to standard therapies alone, the drugs tested in the trial substantially reduced the presence of residual disease in the breast tissue and lymph nodes (known as achieving pathological complete response, or "pCR") when administered before surgery," said Angela DeMichele, MD, MSCE, a professor of Hematology-Oncology and Epidemiology at the Perelman School of Medicine at the University of Pennsylvania, a co-investigator and Chair of Trial Operations for the study, known as I-SPY 2. "pCR strongly predicts prevention of later recurrence of incurable metastatic disease. These results suggest that neratinib and veliparib-carboplatin are very promising treatment options for patients with HER2-positive and , respectively. In addition, the platform used for the I-SPY 2 trial allows the research team to test these and other new therapies simultaneously, targeting tumor subtypes that would be most likely to benefit from the therapies, minimizing the exposure of patients to treatments that are not likely to work for their disease subtype and accelerating drug development"

The data presented in the two NEJM articles shows that when added to standard, neoadjuvant chemotherapy, the combination of the molecularly targeted experimental drug veliparib plus carboplatin showed sufficient improvement to meet the pre-specified threshold for "graduation" from the trial, signifying a high likelihood for success in a modest, confirmatory phase 3 neoadjuvant trial in the triple negative subset. Likewise, the experimental drug neratinib was found to have sufficient improvement in the pCR rate for patients in the HER2-positive/HR-negative subset, that it too was "graduated" from the I-SPY 2 trial.

"Because there are so many subtypes of , and because we always test drugs in the metastatic and then adjuvant setting, finding effective therapies is a very difficult and long process. The I-SPY 2 platform allows therapies to be tested and evaluated in more expeditious, cost-effective ways," said Laura J. Esserman, MD, MBA, a professor of Surgery and Radiology and director of the Carol Franc Buck Breast Care Center at UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, Principal Investigator on the I-SPY 2 trial and a senior author on the reports. "These results provide valuable information on which drugs should proceed to confirmatory trials to improve outcomes for patients with extremely aggressive cancers that put women at risk for early recurrence and death. For these patients, time is of the essence. In particular, finding drug combinations that are effective and less toxic is extremely important. The new studies show that by using the I-SPY 2 model to match therapies with biomarker subsets, we can create trials that are more focused, smaller, and faster, thereby exposing more patients to effective treatments."

A major achievement in the progression of I-SPY 2 has been significantly reducing the time it takes to move forward from initiation of discussions with drug companies to enrollment of the first patients. I-SPY 2 has compressed this timeline from an average timeframe of 18 - 36 months to five months. The I-SPY 2 study start-up period takes approximately 45-60 days, with more than 50 percent of the sites opening and enrolling patients, as opposed to the traditional study start-up timing of 10 to 13 months, with less than 25 percent of the sites opening and enrolling.

More than 45 investigators, from the nation's most prestigious and innovative cancer research centers, co-authored the two NEJM articles, with hundreds of staff and investigators involved in I-SPY 2 overall. In addition to Dr. Esserman, the Principal Investigators for I-SPY 2 is Donald A. Berry, PhD, a professor in the department of Biostatistics at The University of Texas MD Anderson Cancer Center, and founder of Berry Consultants. A complete list of the participating centers and investigators is provided in a Supplementary Appendix available at

Explore further: Neratinib active in HER2-positive, HR-negative breast cancer

Related Stories

Neratinib active in HER2-positive, HR-negative breast cancer

July 7, 2016
(HealthDay)—Neratinib and veliparib-carboplatin appear to be effective in women with specific subtypes of breast cancer, according to two studies published online July 6 in The New England Journal of Medicine.

Innovative trials produce promising breast cancer drugs

July 7, 2016
(HealthDay)—An innovative set of clinical trials have identified two drugs that could provide a fighting chance for women with advanced breast cancer.

New presurgery combination therapy may improve outcomes for women with triple-negative breast cancer

December 13, 2013
The I-SPY 2 trial, an innovative, multidrug, phase II breast cancer trial, has yielded positive results with the first drug to complete testing in the trial. Adding the chemotherapy carboplatin and the molecularly targeted ...

Study shows new paradigm in breast cancer research

December 13, 2013
The first investigator results from an unprecedented nationwide effort to test promising new breast cancer drugs before the tumor is removed were presented during the 2013 San Antonio Breast Cancer Symposium.

Evidence show new drug combination may improve outcomes for women with advanced breast cancer

April 18, 2016
Results from the I-SPY 2 trial show that giving patients with HER2-positive invasive breast cancer a combination of the drugs trastuzumab emtansine (T-DM1) and pertuzumab before surgery was more beneficial than the combination ...

Two groundbreaking studies reflect new paradigm in breast cancer research

July 7, 2016
In a new paradigm of breast cancer research, physicians are fast-tracking promising new experimental drugs for further study, while immediately dropping drugs and drug combinations that don't work.

Recommended for you

Researchers discover specific tumor environment that triggers cells to metastasize

November 21, 2017
A team of bioengineers and bioinformaticians at the University of California San Diego have discovered how the environment surrounding a tumor can trigger metastatic behavior in cancer cells. Specifically, when tumor cells ...

New study points the way to therapy for rare cancer that targets the young

November 21, 2017
After years of rigorous research, a team of scientists has identified the genetic engine that drives a rare form of liver cancer. The findings offer prime targets for drugs to treat the usually lethal disease, fibrolamellar ...

Clinical trial suggests new cell therapy for relapsed leukemia patients

November 20, 2017
A significant proportion of children and young adults with treatment-resistant B-cell leukemia who participated in a small study achieved remission with the help of a new form of gene therapy, according to researchers at ...

Cell-weighing method could help doctors choose cancer drugs

November 20, 2017
Doctors have many drugs available to treat multiple myeloma, a type of blood cancer. However, there is no way to predict, by genetic markers or other means, how a patient will respond to a particular drug. This can lead to ...

Researchers discover a new target for 'triple-negative' breast cancer

November 20, 2017
So-called "triple-negative" breast cancer is a particularly aggressive and difficult-to-treat form. It accounts for only about 10 percent of breast cancer cases, but is responsible for about 25 percent of breast cancer fatalities.

Study reveals new mechanism used by cancer cells to disarm attacking immune cells

November 20, 2017
A new study by researchers at The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute (OSUCCC - James) identifies a substance released by pancreatic cancer cells that protects ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.