February 2016, Vol. 5, No. 1

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Early Results with Immunotherapy in Breast Cancer

Hope S. Rugo, MD

San Antonio Breast Cancer Symposium

Immunotherapy is a hot topic in cancer right now, with approved checkpoint inhibitors for melanoma and non–small cell lung cancer. Checkpoint inhibitors are also making inroads in other solid tumors.

Separate preliminary studies of checkpoint inhibitors in the treatment of breast cancer had less impressive results, but these are early studies, and investigators believe that subsets of patients may benefit from this approach. The following 2 studies were presented at the 2015 San Antonio Breast Cancer Symposium (SABCS).


The JAVELIN trial evaluated the investigational programmed death-1 ligand 1 (PD-L1) inhibitor avelu­mab in patients with locally advanced or metastatic breast cancer. Overall response rate (ORR) was low (4.8%), but it appears that there may be a benefit in the subset of patients with triple-negative breast cancer (TNBC); of the 8 patients who responded in this trial, 5 had TNBC.

Overall, tumor shrinkage of 30% or more was observed in 16 patients (9.5%).

“Despite the modest overall response rate in unselected metastatic breast cancer patients, there were signs of greater clinical activity among patients with triple-negative breast cancer and patients expressing PD-L1. Further analysis of PD-L1 expression and clinical activity of avelumab is ongoing,” according to Luc Dirix, MD, Sint-Augustinus Hospital, Antwerp, Belgium, who presented results.

The 168 patients enrolled in the trial were unselected for PD-L1 expression. Fifty-eight had TNBC, 72 had estrogen receptor–positive (ER+)/HER2-negative or progesterone receptor–positive disease, and 26 had HER2-positive disease; another 12 patients had unknown molecular subtype.

Avelumab 10 mg/kg was administered intravenously every 2 weeks until disease progression.

Response to avelumab appeared to be related to PD-L1 expression on immune cells within the tumor: 33% for those with positive PD-L1 expression versus 2.4% for tumors that were PD-L1 negative. Four of the 5 TNBC responders had PD-L1–positive immune cells.

Safety was acceptable. Grade ≥3 treatment-related adverse events were reported in 13.7% of patients. Immune-related side effects (ie, hypothyroidism, thrombocytopenia, and/or autoimmune hepatitis) were reported in 17 patients. Eight patients (4.8%) discontinued treatment with avelumab. Treatment-related deaths were reported in 2 patients (1.2%). At the time of data cutoff, 9 patients remained on avelumab.


Rugo,Hope98pxPembrolizumab was evaluated in a “basket” trial that included patients with several types of advanced, heavily pretreated solid tumors screened for PD-L1. Of 261 patients in the breast cancer cohort, 48% were PD-L1 positive; among 25 evaluable patients with ER+/HER2-negative PD-L1–positive breast cancers, ORR was 12% (3 partial responders), with another 4 patients (16%) having stable disease. Five patients (60%) progressed on pembrolizumab, and 3 (22%) were not evaluable at the time of SABCS. The clinical benefit rate was 20%.Responses were durable, ranging from 8.7 weeks to more than 44 weeks.

At the time of data cutoff, all 3 partial responders remained on therapy with pembrolizumab.

Lead author Hope Rugo, MD, University of California San Francisco, was upbeat about the study: “Based on these data, we believe that further investigation of immune therapies in HER2-positive, ER-negative breast cancer is warranted, particularly if combination therapies can expand the T-cell compartment,” she told listeners.

Rugo and other investigators at SABCS believe that standardization of PD-L1 assays is very important. Right now, different assays with various cut points are used by different drug companies, confounding interpretation of results. She also pointed out that some PD-L1–negative patients do respond to checkpoint inhibitors, so it is still questionable whether PD-L1 will be a useful biomarker.

Grade 3/4 adverse events were reported in 4 of 25 patients; 4 immune-related grade 3 events occurred, and there was 1 grade 4 event. No treatment-related deaths occurred at a median follow-up of 7.3 months.

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