Adam M. Brufsky, MD, PhD, professor of Medicine, associate chief of Hematology/Oncology, co-director of the Comprehensive Breast Care Center, associate director of Clinical Investigation, University of Pittsburgh, discusses combining cobimetinib (Cotellic) and paclitaxel as a first-line treatment in patients with advanced triple-negative breast cancer (TNBC).

As a MEK inhibitor, cobimetinib may have effectiveness in breast cancer, since there are some growth factor pathways inhibited by MEK, Brufsky explains. Additionally, it is an agent approved by the FDA for patients with melanoma. Therefore, researchers contemplated whether there were possibilities within the basal-2 subtype of TNBC, which has growth factor-differentiating issues.

The COLET trial randomized patients with TNBC to weekly paclitaxel alone or combined with cobimetinib. Overall, there was very little toxicity reported with the combination, he adds. Responses were observed in the first 16 patients, and researchers are still analyzing the remainder of the data. There are approximately 90 patients currently enrolled on the trial.

Results also showed a response rate of around 50%, with a documented 20% to 30% of patients reported to have stable disease.

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Adam M. Brufsky, MD, PhD, professor of Medicine, associate chief of Hematology/Oncology, co-director of the Comprehensive Breast Care Center, associate director of Clinical Investigation, University of Pittsburgh, discusses combining cobimetinib and paclitaxel as a first-line treatment in patients with advanced triple-negative breast cancer.

Dr. Brufsky on Cobimetinib Plus Paclitaxel in TNBC

Adam M. Brufsky, MD, PhD, professor of Medicine, associate chief, Division of Hematology/Oncology, co-director, Comprehensive Breast Cancer Center, associate director, Clinical Investigation, University of Pittsburgh, compares the use of anastrozole to tamoxifen in patients with ductal carcinoma in situ (DCIS).

In a recent study, anastrozole, an aromatase inhibitor, was seen as superior to tamoxifen for the treatment of DCIS. According to prior research, surgical resection of DCIS followed by radiation therapy created a substantial reduction in recurrent DCIS and new cancers. Tamoxifen, Brufsky explains, has demonstrated similar findings. 

Anastrozole had previously been tested as more effective than tamoxifen in invasive cancers. In this study, researchers found that it also decreases recurrence in DCIS by 30-40%, as well as cancers in the opposite breast by another 30-40%. Anastrozole also has less toxicity, Brufsky says, as well as no risk of uterine cancer, and a minimal risk of blood clots.

These findings will likely have a clinical practice, Brusky adds.

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Adam M. Brufsky, MD, PhD, professor of Medicine, associate chief, Division of Hematology/Oncology, co-director, Comprehensive Breast Cancer Center, associate director, Clinical Investigation, University of Pittsburgh, compares the use of anastrozole to tamoxifen in patients with ductal carcinoma in situ (DCIS). 

Dr. Brufsky on Anastrozole Versus Tamoxifen in DCIS

Adam M. Brufsky, MD, PhD, professor of medicine, associate chief, Division of Hematology/Oncology, University of Pittsburgh, discusses whether or not adjuvant bisphosphonates are ready to be a new standard of care in breast cancer.

Brufsky says he believes bisphosphonates are ready to be used in the adjuvant setting. Just as there was a meta-analysis for chemotherapy, there is a meta-analysis for adjuvant bisphosphonates. This analysis showed that 22,000 post-menopausal women experienced a survival benefit and disease-free survival benefit of about 3-4% when taking bisphosphonates. The data from this meta-analysis shows that adjuvant bisphosphonates are as significant as chemotherapy, Brufsky says.

Because of this, Brufsky believes that physicians are ready to use adjuvant bisphosphonates as a standard of care in breast cancer.

Dr. Brufsky on Adjuvant Bisphosphonates for Patients with Breast Cancer

Adam M. Brufsky, MD, PhD, professor of medicine, associate chief, Division of Hematology/Oncology, University of Pittsburgh, discusses future research into bisphosphonates.

The cancer cell itself is incredibly complex, Brufsky says. Much work has been done to understand cancer cells with next-generation sequencing and RNA-based assays.

Drugs like bisphosphonates and denosumab affect the host greatly. Research needs to be conducted focused on the genomics of the host and the factors that allow metastatic disease to come about from the host’s perspective.

Dr. Brufsky Discusses Future Research into Bisphosphonates

Adam M. Brufsky, MD, PhD, professor of medicine, associate chief, Division of Hematology/Oncology, University of Pittsburgh, discusses the results of a phase II study that looked at the effect of prior trastuzumab on eribulin mesylate in combination with trastuzumab as first-line treatment for HER2-positive locally recurrent or metastatic breast cancer.

Eribulin has demonstrated a survival advantage in HER2-negative metastatic breast cancer. In this phase II trial, 52 patients received eribulin and trastuzumab for a median treatment duration of about 30 weeks. Though some patients received prior trastuzumab (n = 21), Brufsky says, objective response rates were high, regardless of treatment with prior trastuzumab (ORR = 62%) or not (ORR = 77%).

Activity has been demonstrated in the first-line, though Brufsky anticipates there will be activity across all lines of therapy.

Adam M. Brufsky, MD, PhD, discusses the effect of prior trastuzumab on eribulin mesylate in combination with trastuzumab as first-line treatment for HER2-positive locally recurrent or metastatic breast cancer.

Dr. Brufsky on Trastuzumab and Eribulin for HER2+ Metastatic Breast Cancer

Adam Brufsky, MD, PhD, FACP, professor of medicine, associate division chief, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, discusses the tnAcity trial, which is aimed to clarify how best to use existing drugs in patients with triple-negative breast cancer (TNBC).

Brufsky says the idea of the tnAcity trial is that while most physicians use gemcitabine and carboplatin, there is not much evidence to support that that is the optimal form of treatment. This trial will measure the efficacy of combinations, such as gemcitabine and carboplatin, carboplatin and nab-paclitaxel (Abraxane), and gemcitabine and nab-paclitaxel. The phase II trial, which has about 80 patients enrolled, will randomize the patients to receive one of the three combinations.

Based on the results of the phase II trial, Brufsky says, the two combinations that prove to be the most effective will be tested. The phase III portion will begin in about a year. Brufsky says the trial will answer a very important question while also investigating biomarkers that will help physicians figure out how to optimally treat patients with TNBC.

Adam Brufsky, MD, PhD, FACP, discusses the tnAcity trial, which is aimed to clarify how best to use existing drugs in patients with triple-negative breast cancer.

Dr. Brufsky Discusses the tnAcity Trial in TNBC

Adam Brufsky, MD, PhD, professor of medicine, associate chief of hematology-oncology, and co-director of the Comprehensive Breast Center at the University of Pittsburgh School of Medicine, discusses the use of bevacizumab (Avastin) for breast cancer patients.

Brufsky explains that the most important advice he can give to other doctors is to use their clinical judgment and do what is right for their patients. Doctors should not succumb to pressure from the community or insurance companies and should do what is best for the patient.

While bevacizumab should not be given to every breast cancer patient it does hold benefits for some. HER2-neu triple-negative breast cancer has limited treatment options and using bevacizumab may be the best therapy available. Reimbursement may become an issue now that the indication has been revoked.

In closing Brufsky adds that doctors should not be scared away by a governmental organization, which he describes as having a different agenda than doctors.

Dr. Adam Brufsky from the University of Pittsburgh School of Medicine Advises Doctors on Bevacizumab (Avastin) for Breast Cancer

Dr. Brufsky Advises Doctors on Avastin for Breast Cancer

Adam Brufsky, MD, PhD, professor of medicine, associate chief of hematology-oncology, and co-director of the Comprehensive Breast Center at the University of Pittsburgh School of Medicine, discusses the benefits of second-line bevacizumab (Avastin) when added to standard chemotherapy in metastatic triple-negative breast cancer (TNBC) patients.

The RIBBON-2 trial examined 684 HER2-negative locally advanced or metastatic TNBC patients. These patients were given bevacizumab in addition to the physician's choice of a second-line chemotherapy.

The median progression-free survival for the bevacizumab arm of the trial was 6.0 months compared to 2.7 months for patients on chemotherapy alone. The reduction in risk was 51% with an objective response rate of 41% for those receiving bevacizumab.

Dr. Adam Brufsky from University of Pittsburgh School of Medicine, Discusses Bevacizumab Benefits in TNBC

Adam M. Brufsky, MD, PhD

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