Julia Tchou, MD, PhD, on Triple-Negative Breast Cancer: Radiation Boost Plus Pembrolizumab
Julia Tchou, MD, PhD, of the University of Pennsylvania, discusses preliminary results of the phase Ib/II BreastVax study, which suggested a single preoperative pembrolizumab dose plus a tumor-targeting radiation boost may result in pathologic response in patients with early-stage triple-negative breast cancer (Abstract 644).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The reason why we think a single dose of Pembrolizumab plus a tumor-targeted radiation may work in patients with early-stage breast cancer is that we know that immune checkpoint inhibitor alone or as monotherapy does not work in breast cancer. We also know that we have to combine pembrolizumab with an immune stimulant such as chemotherapy, but because we really want to try to omit chemotherapy to deescalate treatment in this special population, which is early-stage breast cancer, we think that a single fraction of radiation boost may be effective as a combination with a single dose of Pembrolizumab prior to surgery.
The study is a window of opportunity study. We are evaluating three treatment arms prior to surgery. The arms one and two to examine the combination of radiation boost plus pembrolizumab. The difference between arm one and two is the sequence of the timing of the radiation versus pembrolizumab.
Arm one is radiation boosts first followed by pembrolizumab. Arm two is Pembrolizumab first, followed by radiation boost. And then the third arm is to evaluate pembrolizumab alone. That's the treatment. The three arms that we want to evaluate. And we want to look at this in patients with early-stage breast cancer without high risk features so that we can test whether this radiation combination with immunotherapy may be effective in this patient population.
So far, 13 patients have completed the study and 10 patients have triple-negative breast cancer. Among the 10 patients with triple-negative breast cancer, we observe that three patients have major response defined as tumor shrinkage. Of the three patients with significant tumor shrinkage, the tumor shrunk by about 80% or more. And in the three patients, one patient had complete pathologic response after a single dose of Pembrolizumab and one single tumor-targeting radiation given prior to surgery.
The next step is to continue to enroll patients into this study because this is considered still a very small sample size. We want to enroll more patients so that we can confirm our preliminary results, and we want to do additional molecular analysis to identify biomarkers associated with treatment response so that we can get to the next step to open a second study that look at patients with even earlier-stage disease.
Kishu Ranjan, PhD, of Yale University School of Medicine, discusses his study findings, which identified a deficiency in the biomarker TAP2 as a prominent immune evasion mechanism in patients whose non–small cell lung cancer has resisted immunotherapy (Abstract 148).
Antoni Ribas, MD, PhD, of the University of California, Los Angeles, discusses a phase I study that used CRISPR gene editing to simultaneously “knock out” endogenous T-cell receptors and replace them with personalized neoantigen T-cell receptors in patients with solid tumors. The edited TCR T-cell products were safely infused and trafficked to the tumor lesions (Abstract 1478).
Jonathan Chen, MD, PhD, of Massachusetts General Hospital, discusses “immunity hubs” that interact with a reservoir of stem-like CD8 T cells and appear to be associated with subsequent response to anti–PD-1 blockade in patients with non–small cell lung cancer. Hybrid hubs, Dr. Chen says, are a favorable class of immunity hub notable for CD8-positive and TCF7-positive cells, as well as CCL19 expression (Abstract 956).
Michael B. Atkins, MD, of Georgetown Lombardi Comprehensive Cancer Center, explores recent clinical trials in immuno-oncology in which the phase III trial produced markedly different results from the phase II trial. To help understand the potential value to patients of late-stage trials of treatment combinations, the Society for Immunotherapy of Cancer has developed a checklist for investigators, applicable to any regimen in which immune modulation is an important component of the antitumor effect.
Wade T. Iams, MD, of Vanderbilt University Medical Center, discusses phase II efficacy results from the first-line non–small cell lung cancer cohort of the TACTI-002 study. The results suggest that when combined with pembrolizumab, eftilagimod alpha yielded encouraging efficacy across all PD-L1 levels, including patients with PD-L1 low and PD-L1 negative disease (Abstract 1470).