New Drug Shows Promise for Metastatic Triple-Negative Breast Cancer Patients Who Have Already Taken Previous Treatments

The gist: A drug called sacituzumab govitecan has shown promising results in a clinical trial in patients with metastatic triple-negative breast cancer (TNBC) who have taken previous treatments. In the trial, patients generally experienced a longer period of time without their cancer worsening when they took sacituzumab govitecan compared to when they took their last treatment for TNBC.

Immunomedics, Inc. , (Nasdaq:IMMU) today announced that sacituzumab govitecan, the Company’s novel investigational antibody-drug conjugate (ADC), continues to produce a partial response (PR) rate of 30% and a 70% clinical benefit rate (CBR), defined as PR and stable disease, in patients with metastatic triple-negative breast cancer (TNBC) who had been heavily pretreated. For patients with PR or stable disease longer than 6 months, the CBR was 40%. Significantly, PRs ranging from 30% to 70% tumor shrinkage as best response were reported. Responses are measured by computed tomography (CT) based on RECIST 1.1 criteria.

“Dr. Aditya Bardia of Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, presented the Phase 1/2 study at the San Antonio Breast Cancer Symposium in San Antonio, TX. Commenting on the results, Dr. Bardia stated, ‘TNBC patients in this late-stage setting have limited treatment options that are effective. We are quite encouraged with this experience with sacituzumab govitecan, especially the time-to-progression results, which showed that the duration of response for the responding patients was generally longer than their last prior therapy for TNBC.’ ”

“As the name implies, TNBC represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women. Despite the fact that initial responses with chemotherapy are high, TNBC characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. According to a published report, the median survival for patients with metastatic triple-negative breast cancer is estimated to be 13 months. 1 Currently, there are no targeted treatments available for TNBC.”


Weekly Paclitaxel or Docetaxel Every 3 Weeks Improves Survival in Breast Cancer

The gist: A different treatment schedule after surgery might increase survival and time without cancer worsening for women with axillary node-negative or high-risk node-negative breast cancer. A clinical trial found that these women might benefit from taking the drug paclitaxel once per week or docetaxel once every three weeks, instead of paclitaxel once every three weeks. The same trial found that women with triple negative breast cancer (TNBC) also benefit from weekly paclitaxel. But docetaxel once every three weeks showed better results for women with ER-positive, HER2–negative breast cancer.

“Women with axillary node-negative or high-risk node-negative breast cancer achieved prolonged DFS and marginally improved OS when they received adjuvant paclitaxel every week or docetaxel every 3 weeks compared with paclitaxel every 3 weeks, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

“Further, weekly paclitaxel extended DFS and OS in women with triple-negative breast cancer, whereas docetaxel administered every 3 weeks improved DFS in women with ER-positive, HER-2–negative disease.

“Joseph A. Sparano, MD, professor of medicine and women’s health at Albert Einstein College of Medicine, and colleagues evaluated various regimens in 4,954 women with axillary node-positive or high-risk node-negative breast cancer. Previously released results, based on a median 5.3 years of follow-up, showed those who received adjuvant weekly paclitaxel (HR=0.73; P=.0006) or docetaxel every 3 weeks (HR=0.77; P=.02) demonstrated longer DFS than women who received paclitaxel every 3 weeks.

“The current analysis occurred after a median 12.1 years of follow-up. The numbers of DFS events (1639 vs. 1048) and deaths (1283 vs. 686) in the current analysis vs. the previous report were substantially higher.”


Prostate Cancer Drug Xtandi Shows Promise for Treating Advanced, AR+ Triple-Negative Breast Cancer

The gist: A prostate cancer drug called Xtandi (aka enzalutamide) might also help treat women with advanced, androgen receptor-positive triple-negative breast cancer (TNBC). More research will need to be done to see whether Xtandi outperforms standard chemotherapy for these patients.

“Preliminary results from a Phase II trial of Astellas’ Xtandi (enzalutamide) show positive benefits for the prostate cancer drug when used as a single therapy to treat women with advanced androgen-receptor positive, triple-negative breast cancer.

“But Novartis’ bid to prove benefits for Afinitor (everolimus) as a first-line treatment for women with HER2-positive advanced breast cancer failed, after a Phase III trial found no benefit in this group of patients. [See more here.]

“The data from both studies were presented at the San Antonio Breast Cancer Symposium in Texas. The trial involving Xtandi is the largest to date in patients with androgen-receptor positive triple-negative breast cancer, and the first to report objective responses to a hormonal therapy.

“The study found that out of 26 women evaluated, 11 showed a clinically significant benefit after 16 weeks and 9 showed benefit after 24 weeks. More data is due in 2015 from a further 76 women enrolled in the study, but so far researchers have observed positive responses in one woman and partial positive responses in three more women in this group.”


What's Intriguing And Concerning About Early Results For Keytruda In Breast Cancer

Note: This is an opinion piece about the recent news that the drug Keytruda has shown promise for treating triple-negative breast cancer (TNBC). It does not necessarily reflect the views of Cancer Commons.

“At first glance, it’s hard to get excited about the preliminary results of an early phase trial study of pembrolizumab (Keytruda, MK-3475) in women with triple-negative breast cancer (TNBC). The non-randomized study has, so far, yielded an overall response rate of 18.5 percent – only 5 among 27 evaluable patients.

“The findings drew attention at the San Antonio Breast Cancer Symposium, in part because TNBC is a notoriously hard-to-treat form of the disease. The work* was presented by Dr. Rita Nanda, of the University of Chicago, who led a multinational list of authors including academics and several Merck employees.

“Keytruda is a monoclonal antibody given by infusion. When it binds PD-1, as it’s engineered to do with high affinity, it can unleash the body’s normal immune cells to fight a tumor. Recently, the FDA approved Keytruda for use in advanced melanoma. Last week, at the annual meeting of the American Society of Hematology, investigators reported preliminary findings that the drug is well-tolerated and may be helpful in Hodgkin’s lymphoma.”


Phase III Results Demonstrate Significant Pathological Complete Response for Nab-Paclitaxel in Neoadjuvant Breast Cancer–

The gist: The drug nab-paclitaxel (aka Abraxane) has shown promise for patients with early-stage, high-risk breast cancer. Nab-paclitaxel is an injectable version of the chemotherapy drug paclitaxel. In a clinical trial, tumors disappeared in 38% of the patients who took nab-paclitaxel, compared to 29% of patients who took conventional paclitaxel. Learn more about the treatment, and its side effects, here.

“The German Breast Group (GBG) said nab-paclitaxel (ABRAXANE®) demonstrated significant benefit for patients with early high risk breast cancer when compared to conventional solvent-based paclitaxel. The findings are from the GeparSepto clinical trial sponsored by GBG and conducted together with the German AGO-B study group involving over 1200 patients, which is the largest randomized Phase III study ever completed with nab-paclitaxel and the first one completed in high risk early breast cancer. The results were presented by the coordinating investigator Michael Untch, M.D., Berlin in General Session 2 on December 10th, at the 2014 San Antonio Breast Cancer Symposium.

“The study found a statistically significant and clinically meaningful 9% absolute improvement from 29% to 38% (p=<0.001) in the pCR (pathological complete response) rate, when neoadjuvant (preoperative) chemotherapy was started with nab-paclitaxel instead of conventional solvent-based paclitaxel followed by epirubicin/cyclophosphamide given all before surgery. Pathological complete response after neoadjuvant treatment for breast cancer is a surrogate marker for long-term efficacy.

“ ‘The phase III study provided a head-to-head comparison of weekly nab-paclitaxel with weekly conventional paclitaxel followed by epirubicin/cyclophosphamide in both arms before surgery. Our findings clearly demonstrate nab-paclitaxel is superior to paclitaxel in achieving pCRs in early high risk breast cancer,’ Prof. Dr. Michael Untch.”


Early Trial of New Drug Shows Promise for Patients with Triple-Negative Breast Cancer

The gist: A drug called pembrolizumab (aka Keytruda or MK-3475) has shown promise for people with metastatic triple-negative breast cancer (TNBC) whose tumors have high levels of a protein called PD-L1.  It was recently tested in patients in a clinical trialPembrolizumab is already approved by the U.S. Food and Drug Administration (FDA) for treating melanoma. It is an immunotherapy, meaning that it boosts a patient’s own immune system to fight cancer. More research will determine just how well pembrolizumab might work for TNBC.

“In patients with metastatic triple-negative breast cancer—a disease with no approved targeted therapies—infusion of pembrolizumab produced durable responses in almost one out of five patients enrolled in a phase-Ib clinical trial, according to data presented Dec. 10, at the 2014 San Antonio Breast Cancer Symposium.

“The multi-center, non-randomized trial was designed to evaluate the safety, tolerability and antitumor activity of bi-weekly infusions of pembrolizumab (MK-3475, marketed as Keytruda®). The researchers enrolled 27 patients, aged 29 to 72 years, who had metastatic triple-negative breast cancer that either relapsed after treatment for early stage disease or progressed on therapy for advanced disease.

” ‘For this group of patients our treatment options are limited to chemotherapy,’ said study director Rita Nanda, MD, assistant professor of medicine and associate director of the breast medical oncology program at the University of Chicago.

“All patients in the study had triple-negative tumors with high levels of a protein called programmed death-ligand 1 (PD-L1). This protein can suppress the immune system’s efforts to eliminate cancer cells. Pembrolizumab is a monoclonal antibody designed to help reactivate a person’s own immune system to help fight the tumor.”


Toughest Breast Cancer May Have Met Its Match

The gist: This article discusses a potential way to improve chemotherapy treatment for triple-negative breast cancer (TNBC), but it has only been tested in mice so far, so it is not yet known whether it would work for humans. The method would use drugs called HIF inhibitors to make breast cancer cells more responsive to chemotherapy. HIF inhibitors are already being used in humans with other conditions, so clinical trials may soon be able to show whether they work for TNBC.

“Triple-negative breast cancer is as bad as it sounds. The cells that form these tumors lack three proteins that would make the cancer respond to powerful, customized treatments. Instead, doctors are left with treating these patients with traditional chemotherapy drugs that only show long-term effectiveness in 20 percent of women with triple-negative breast cancer. Now, researchers at The Johns Hopkins University have discovered a way that breast cancer cells are able to resist the effects of chemotherapy—and they have found a way to reverse that process.

“A report of their findings was published online in the journal Proceedings of the National Academy of Sciences on Dec. 1.

“Triple-negative breast cancers account for about 20 percent of all breast cancers in the United States, and 30 percent of all breast cancers in African-American women. In addition to being resistant to chemotherapy, they are known to include a high number of breast cancer stem cells, which are responsible for relapses and for producing the metastatic tumors that lead to the death of patients with cancer. Previous research revealed that triple-negative breast cancer cells show a marked increase in the activity of many genes known to be controlled by the protein hypoxia-inducible factor (HIF). Given these past results, a research team directed by Gregg Semenza, M.D., Ph.D., decided to test whether HIF inhibitors could improve the effectiveness of chemotherapy.”