Pembrolizumab Improves Response Rates In Women With Early-Stage Breast Cancer

Pembrolizumab added to neoadjuvant chemotherapy improves pathologic complete response (pCR) rates in women with early-stage breast cancer, according to results from the ongoing I-SPY2 trial.

"While we were hoping to see the improvement in estimated pCR rates in women with triple-negative breast cancer (TNBC), that we also saw a more than doubling in the estimated pCR rates in women with Mammaprint high-risk, hormone receptor (HR)+/HER2-breast cancer was very exciting," Dr. Rita Nanda of the University of Chicago told Reuters Health by email.

Pembrolizumab is a highly selective, humanized IgG4 monoclonal antibody specific for programmed cell death protein (PD)-1 that is approved for use in a number of advanced malignant diseases. Studies of its use as monotherapy in breast cancer have yielded mixed results.

Dr. Nanda and colleagues evaluated the efficacy of adding pembrolizumab to standard neoadjuvant chemotherapy in the phase 2 adaptively randomized I-SPY2 trial, which is evaluating multiple investigational arms in parallel and whose primary endpoint is pCR, defined as the absence of invasive tumor in breast and regional nodes at the time of surgery.

This analysis included 69 patients randomized to pembrolizumab and 181 patients randomized to the control arm of the study. Two patients on pembrolizumab and seven patients in the control arm were counted as non-pCR, as they did not proceed to surgery.

Estimated pCR rates for pembrolizumab and control arms were 44% vs 17%, respectively, for ERBB2-negative tumors, 30% vs 13% for HR-positive/ERBB2-negative tumors, and 60% versus 22% for TNBC, the researchers report in JAMA Oncology.

Event-free survival was qualitatively similar between the pembrolizumab and control arms in an exploratory analysis.

Immune-related toxic effects were more common in the pembrolizumab arm than in the control arm, with notable increases in adrenal insufficiency (8% vs. none in the control arm), hepatitis (2.9% vs. none) and thyroid dysfunction (13.0% vs. none).

"Based on the significant improvement in pCR rate observed in the follow-up randomized phase-3 KEYNOTE 522 trial, there is a role for pembrolizumab in the early-stage setting," Dr. Nanda said. "It is my hope that pembrolizumab plus chemotherapy will gain regulatory approval for those with early-stage TNBC. TNBC is associated with a poor prognosis, and pembrolizumab is well-tolerated with manageable side effects."

"The KEYNOTE 756 randomized phase 3 trial of pembrolizumab plus chemotherapy for those with early-stage, high-risk HR+ breast cancer is ongoing, and if this study demonstrates a significant improvement in outcomes, pembrolizumab could very well be incorporated into the early-stage setting for high-risk, HR+ disease as well," she said.

Dr. Nanda and several of her coauthors report ties to Merck, which provided the study drug and was permitted to review the manuscript prior to submission, but played no role in the design and conduct of the study, interpretation of the data, preparation or approval of the manuscript or decision to submit it for publication.

—Will Boggs MD.

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