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 potential of novel combination strategies with checkpoint inhibitors in oncology.

Ongoing trials are evaluating PD-L1 inhibitors in combination with novel therapies, such as TIGIT- and LAG-3–directed antibodies, says Burris. Early data have shown improved activity with combination regimens compared with single-agent checkpoint inhibitors. Additionally, these novel therapies appear to improve activity versus single-agent treatment in patients who have received prior checkpoint inhibitors, Burris explains. 

Moreover, these benefits have been observed across a wide section of oncology, including lung cancer, colon cancer, and melanoma, says Burris. As such, the potentially diverse application of these therapies is an exciting research effort to keep an eye on in 2021.

Videos

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses the potential of novel combination strategies with checkpoint inhibitors in oncology.  



Dr. Burris on the Potential for Novel Checkpoint Inhibitor Combinations in Oncology 

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 ​treatment considerations in triple-negative breast cancer (TNBC).

Patients with TNBC should be considered for clinical trials, says Burris. Notably, several emerging agents are showing encouraging data in the relapsed/refractory setting.

Moreover, it’s of critical importance for this group of patients to undergo molecular profiling because it can help identify 

or DNA damage repair mutations, high tumor mutational burden, or PD-L1 overexpression.

​Additionally, molecular information can inform therapy selection; thus, patients are encouraged to undergo molecular profiling, Burris concludes.

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses ​treatment considerations in triple-negative breast cancer.

Dr. Burris on Treatment Considerations in TNBC  

Howard A. "Skip" Burris, III, MD, FASCO, FACP, chief medical officer and president, Clinical Operations, Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care

 in Drug Development, discusses investigational immunotherapy approaches in triple-negative breast cancer (TNBC).

Data from the phase III KEYNOTE-522 trial, which were presented at the 2019 ESMO Congress and 2019 San Antonio Breast Cancer Symposium (SABCS), showed that the addition of the PD-1 inhibitor pembrolizumab (Keytruda) to neoadjuvant chemotherapy increased the pathologic complete response (pCR) rate in patients with TNBC, irrespective of lymph node involvement.

Specifically, data from the 2019 ESMO Congress showed that the pCR rate was 64.8% with pembrolizumab plus chemotherapy versus 51.2% with chemotherapy alone. Although the benefit was observed irrespective of PD-L1 expression, investigators saw greater activity with pembrolizumab in patients with higher PD-L1 expression, says Burris. At the 2019 SABCS, the pCR rate among patients whose disease had spread to the lymph nodes was 64.8% and 44.1% with pembrolizumab and chemotherapy, respectively.

Furthermore, data from the phase I/II TOPACIO/KEYNOTE-162 trial, which combined niraparib (Zejula) with pembrolizumab appear encouraging, adds Burris. Among 60 evaluable patients, the objective response rate was 25%; this rate increased to 45% among the 11 evaluable patients with 

Howard A. "Skip" Burris, III, MD, FASCO, FACP, chief medical officer and president, Clinical Operations, Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses investigational immunotherapy approaches in triple-negative breast cancer (TNBC).

Dr. Burris on Investigational Approaches in TNBC

Howard A. "Skip" Burris, III, MD, FASCO, FACP, chief medical officer and president, Clinical Operations, Sarah Cannon Research Institute, 2019 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses ongoing research with antibody-drug conjugates (ADCs) in triple-negative breast cancer.

ADCs enable patients to receive chemotherapy for a longer period of time and in a better-tolerated fashion, says Burris. As such, patients won’t have to stop treatment due to adverse events. If an antibody binds well to the receptor on a cancer cell, the drug should not require much cytotoxic impact. Such is the case with some of the newer ADCs, adds Burris.

With regard to sacituzumab govitecan, the camptothecin background is attractive, says Burris, although they’ve historically not been used in a large way in breast cancer. Ladiratuzumab vedotin (SGN-LIV1A) is another ADC that has a tubulin inhibitor backbone. In an attempt to further reduce the toxicity of the therapy, investigators may want to look at giving that agent earlier when patients don’t have cumulative toxicity from prior taxane therapy, concludes Burris.

Howard A. "Skip" Burris, III, MD, FASCO, FACP

Articles

Dr. Burris on the Potential for Novel Checkpoint Inhibitor Combinations in Oncology

Dr. Burris on Treatment Considerations in TNBC

Dr. Burris on Investigational Approaches in TNBC

Dr. Burris on Ongoing Research With ADCs in TNBC