The San Antonio Breast Cancer Symposium (SABCS), held on December 10th to the 14th, welcomed thousands of physicians, researchers, patient advocates, and healthcare professionals from around the world. In the field of cancer research, SABCS is among three major annual meetings that provide a forum for researchers across all disciplines to present new and emerging data to the scientific community for open discussion, feedback, and debate.
Here we present updates on the use of immunotherapy for breast cancer.
Atezolizumab, a PD-L1 (checkpoint) inhibitor, was approved in combination with chemotherapy for advanced triple negative breast cancer (TNBC) in March 2019. Efforts are ongoing to determine the efficacy of adding checkpoint inhibitor therapy earlier in treatment—for instance, during neoadjuvant (pre-surgical) therapy. In this setting, patients who achieve a pathological complete response (pCR, or no evidence of tumor at the time of surgery) typically have a better prognosis. For this reason, pCR is a primary outcome in neoadjuvant trials. Updates from two such clinical trials were presented at SABCS.
Preliminary report from NeoTRIPaPDL1 (NCT02620280).
NeoTRIPaPDL1 is a phase III open-label, multicenter trial to test the combination of atezolizumab plus chemotherapy in the neoadjuvant setting in patients with early high-risk and locally advanced or inflammatory TNBC. In preliminary results, the study investigators did not see a significant improvement in pCR with the combination therapy. However, as in the IMPASSION 130 study, which led to the approval of atezolizumab in advanced TNBC, the presence of the PD-L1 protein was the most significant predictor of response. Presenting the results for the study investigators, BCRF researcher Luca Gianni, MD, stressed that while the difference in pCR did not meet certain pre-defined criteria, the benefit of adding atezolizumab may be seen in further analysis.
Findings from KEYNOTE-522 (NCT03036488).
This is a randomized Phase III study evaluating the efficacy and safety of pembrolizumab—another PD-L1 targeted immunotherapy drug—plus chemotherapy compared to chemotherapy plus placebo in newly diagnosed patients with TNBC, also in the neoadjuvant setting. Chemotherapy is standard treatment for TNBC, and studies have shown that TNBC patients who respond well to neoadjuvant chemotherapy have a better prognosis with less likelihood of recurrence than patients with tumors who do not respond.
Results on pCR from KEYNOTE were presented at the European Society for Medical Oncology (ESMO) Congress in 2019. Researchers reported a more than 13 percent improvement with pembrolizumab plus chemotherapy versus chemotherapy alone after approximately 15 months of patient follow-up. Results presented at SABCS were consistent with the ESMO report, showing a significant improvement in pCR across stages of disease including patients with locally advanced disease. The study is ongoing.
Discussion of new immunotherapy studies, including two funded by BCRF.
As we strive to see the same results with immunotherapy in breast cancer that have been reported in other cancers, understanding how patients on immunotherapy are responding will be important. Elizabeth Mittendorf, MD, PhD, from Brigham and Women’s Hospital, discussed the future of immunotherapy in breast cancer and emphasized the BCRF-funded TRIBUTE study. The TRIBUTE study will establish a repository of clinical data, biospecimens, and imaging results that will allow researchers to better understand how immunotherapy is working in the context of routine clinical care and how best to optimize responses to improve immunotherapy in breast cancer.
In the same discussion, Dr. Mittendorf mentioned another BCRF-funded study called AVIATOR. This study is funded through the BCRF Drug Research Collaborative and led by Ian Krop, MD, PhD, at Harvard Medical School. AVIATOR is bringing immunotherapy to other subtypes of cancer, in particular HER2-positive breast cancer. This trial is the first to combine targeted HER2 therapy with immunotherapy and will provide important predictive biomarker data.
In 2019-2020, BCRF is supporting 55 projects, more than $14.5 million, aiming to advance immunotherapy in breast cancer.
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