Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, and a 2014 Giant of Cancer Care® in Drug Development, discusses ​the utility of sacituzumab govitecan-hzi​y (Trodelvy) in metastatic triple-negative breast cancer (TNBC).

granted accelerated approval on April 22, 2020

, sacituzumab govitecan has been used safely and effectively in ​the clinical setting for this patient ​population, says Burris​. However, premedication with antiemetics is often necessary. 

Additionally, the agent has demonstrated several encouraging ​efficacy signals, such as improved liver function ​tests and cancer-related symptoms​, Burris explains.

Notably, the camptothecin toxin in sacituzumab govitecan has always been an agent of interest due to its active payload in irinotecan. ​As such, the mechanism of linking the toxin to an antibody suggests that patients will benefit significantly from this therapy, Burris concludes.

Videos

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses ​the utility of sacituzumab govitecan-hzi​y in metastatic triple-negative breast cancer.

Dr. Burris on the Utility of Sacituzumab Govitecan in Metastatic TNBC  

Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer (TNBC).

In the phase 3 IMpassion130 trial, investigators are examining atezolizumab (Tecentriq) in combination with paclitaxel in patients with TNBC. The biomarkers used in this study are helping the field to understand which patients might benefit from immunotherapy plus chemotherapy, says Burris.

There are now several opportunities to think about PD-L1 overexpression, tumor mutational burden, and microsatellite instability in this setting; this brings up the idea of cell death. It is known that chemotherapy works fairly well in TNBC, although adverse effects and how long the combination therapy can be administered are questions that still need to be addressed, concludes Burris. 

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer.

Dr. Burris on Predictive Biomarkers for Chemoimmunotherapy in TNBC

Howard A. “Skip” Burris, MD president of Clinical Operations and chief medical officer at Sarah Cannon Research Institute, discuses the MARIANNE trial in advanced HER2-positive breast cancer.  

In the overall study results, patients with locally advanced or untreated metastatic HER2-positive disease were randomized to receive T-DM1 plus pertuzumab (Perjeta), T-DM1 alone, or trastuzumab (Herceptin) plus a taxane-based agent. Phase III results of the trial showed that neither T-DM1 arm was associated with improved outcomes compared with the trastuzumab/taxane arm.

However, in patient-reported outcomes of the trial, patients with advanced HER2-positive breast cancer who received treatment with trastuzumab emtanzssine were found to have a lower incidence of treatment-related adverse events.

These means that trastuzumab emtanzssine is still a good option for patients with advanced HER2-positive breast cancer, says Burris.

Dr. Howard Burris on Patient-Reported Outcomes of MARIANNE

Howard Burris, III, MD, Giant of Cancer Care in Drug Development, chief medical officer and executive director of Drug Development at the Sarah Cannon Research Institute, discusses the importance of the ASCO annual meeting, taking place May 29 - June 2.

One of the biggest benefits of ASCO’s annual meeting is the world’s thought-leaders coming together to present, discuss, and debate the latest results and research in cancer, says Burris. However, the ‘hallway conversations’ that happened amongst attendees and presenters off of the podium are just as meaningful. A lot of ideas and collaborations throughout the industry occur this way, he says.

At this year’s conference, Burris is most looking forward to research regarding the harnessing of the immune system to fight cancer. This is an area that has been discussed abstractly for many years, but only recently became a topic in which concrete data was presented at ASCO, says Burris.

View more from the 2015 ASCO Annual Meeting

Howard Burris, III, MD, chief medical officer and executive director of Drug Development at the Sarah Cannon Research Institute discusses the importance of the ASCO annual meeting, taking place May 29 - June 2.

Dr. Burris on the Impact of the ASCO Annual Meeting 

Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses the mammalian target of rapamycin (mTOR) inhibitor everolimus (Afinitor) for patients with HER2-negative breast cancer.

Burris believes that the addition of everolimus to the endocrine therapy combination strategy is going to be very important for managing patients with breast cancer. A substantial uptake in its use in the clinic has already been observed, since the FDA approval in July.

Targeting mTOR has caused a great deal of enthusiasm and sparked new clinical trials, Burris explains. He adds that everolimus will likely be the go-to therapy for patients receiving aromatase inhibitors who have progressed slowly or have not experienced a visceral crisis.

As more research is conducted, Burris expects everolimus will eventually move forward in many sequences as its efficacy is demonstrated both in the clinic and trials.

Dr. Howard Burris, from the Sarah Cannon Research Institute, Discusses the mTOR Inhibitor Everolimus for HER2-Negative Breast Cancer.

Dr. Howard Burris Discusses the mTOR Inhibitor Everolimus

Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses the correlation between pathological complete response (pCR) and Oncotype DX recurrence scores (RS).

A phase II study that examined ixabepilone and cyclophosphamide as neoadjuvant therapy in HER2-negative breast cancer patients found that patients with a high RS (greater than 31) or rapidly proliferating tumors responded better to chemotherapy, with 26% demonstrating a pCR. None of the patients in the trial with a low to intermediate RS experienced pCR.

The trial demonstrated that rapidly proliferating tumors are more susceptible to chemotherapy. Biologics may make a difference and still needs to be explored further in future clinical trials.

Dr. Howard Burris from Sarah Cannon Research Institute Discusses Recurrence Scores Predicting pCR

Dr. Burris on Using Recurrence Scores to Predict pCR

Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses the need for patient population stratification in breast cancer trials.

HER2-positive breast cancer has a tendency to grow very rapidly with each case presenting similar growth characteristics, whereas hormone-receptor sensitive, or ER-positive, breast cancer comes in many different shapes and sizes. Some types of ER-positive breast cancers grow very rapidly and others contain bone complications or visceral metastases. These populations represent unique disease types and each reacts to treatment differently.

In the case of mTOR inhibitors, Burris explains that a retrospective analysis of the original first-line temsirolimus (Torisel) phase III trial shows that it contained a very heterogeneous group of patients.

The stratification of a patient population creates a more homogenous group, which provides a more exact patient profile and aids the discovery of the most beneficial treatment. Burris believes it is best to stratify ER-positive patients into various groups, since the disease has a tendency to be very heterogeneous.

Dr. Howard Burris, from the Sarah Cannon Research Institute, Discusses the Stratification of Clinical Trials

Dr. Burris Discusses the Stratification of Clinical Trials

Howard A. "Skip" Burris, III, MD, chief medical officer and executive director, Drug Development Program, Sarah Cannon Research Institute in Nashville, Tennessee, discusses successful clinical applications for the inhibition of the mammalian target of rapamycin (mTOR) pathway.

Temsirolimus was the first mTOR inhibitor to gain approval for metastatic renal cell carcinoma (RCC). The inhibitors ability to affect the cell cycle, angiogenesis, and proliferation allows it to play multiple roles in the treatment process.

The mTOR agent everolimus (Afinitor), which is also approved for RCC, demonstrated positive results in endocrine cancers. The BOLERO-2 trial demonstrated the efficacy of everolimus for hormone receptor-positive metastatic breast cancer when used in combination with exemestane.

Burris notes that recent studies have shown that blocking more than one pathway is an attractive option, especially for breast cancer. The PI3K/AKT/mTOR pathway plays an important role because the mutation, upregulation and overexpression of PI3K and AKT and the loss of PTEN sets this pathway up as a driver for breast cancer proliferation.

Other pathways work alongside mTOR, including HER2 and hormonal pathways. Dual blockade of mTOR and its neighboring pathways has demonstrated benefits in clinical trials. Burris suggests that blocking the PI3K/AKT/mTOR stream with an mTOR inhibitor is a reasonable opportunity to improve treatment.

Dr. Howard Burris, from the Sarah Cannon Research Institute, Discusses Targeting the mTOR Pathway

Howard A "Skip" Burris, III, MD

Articles