The results from the I-SPY 2 TRIAL investigating Keyytruda (pembrolizumab), in combination with standard therapy as a pre-operative (neoadjuvant) treatment for patients with locally advanced breast cancer were released at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.  The estimated pathologic complete response (pCR) rate increased nearly threefold in patients with triple-negative breast cancer (TNBC).

Approximately 12% of all breast cancers are TNBC, meaning that they are estrogen-receptor negative (ER-), progesterone-receptor negative (PR-), and human epidermal growth factor receptor 2-negative (HER2-). This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.

Unfortunately, many available and effective treatment options for the majority of breast cancers block the growth stimulating effects of ER, PR and/or HER2; therefore, TNBC has had limited therapeutic options.

In addition, TNBC tends to be an aggressive type of cancer, is often diagnosed at a more advanced stage, and proportionately affects younger women more often than other breast cancers. Novel treatment options for TNBC have lagged behind that of other types of breast cancers.

The cancer immunotherapy strategy known as programmed cell death 1 (PD-1) has generated great excitement for its ability to help the immune system recognize, and attack cancer. PD-1 is a protein that inhibits certain types of immune responses. Drugs that block PD-1 are called checkpoint inhibitors and may enhance the ability of the immune system to fight cancer.  Keytruda is a fully humanized monoclonal antibody that binds with high-affinity to the PD-1 receptor.

Clinical evidence to date in other cancers is impressive and suggests that Keytruda® and other checkpoint inhibitors such Opdivo (nivolumab), and Yervoy® (ipilimumab) are very effective in melanoma, lymphoma and lung cancer.2-5

The I-SPY 2 clinical trial, sponsored by Quantum Leap Healthcare Collaborative, is a standing Phase 2 clinical trial for women with newly diagnosed, locally advanced breast cancer (Stage II/III), and is designed to screen promising new treatments and identify which therapies are most effective in specific patient subgroups based on molecular characteristics (biomarker signatures).

The trial is an adaptive study design assessing the combination of biologically targeted investigational drugs with standard chemotherapy in the neoadjuvant setting, compared to standard chemotherapy alone. The primary endpoint is to determine whether the combination of certain therapies increases the probability of pCR in the breast and the lymph nodes at the time of surgery.

In the trial patients were treated with standard weekly chemotherapy; paclitaxel for 12 weeks, combined with or without Keytruda, followed by doxorubicin and cyclophosphamide (AC) every 3 weeks for four cycles. Currently 69 patients were treated with Keytruda and 46 have undergone surgery, while the other 23 had an on-therapy MRI assessment or response to treatment.

Overall patients with TNBC had an estimated pCR of 60%.  All HER2 negative patients had a response rate of 46% and HER2 negative hormone receptor positive patients had a response rate of 34%.

Individuals with TNBC achieved an absolute increase in the estimated response of 40% with the addition of Keytruda over the historical experience of 20% with standard therapy alone.

Keytruda in combination with standard therapy tripled the rate of pathologic complete responses in HER2- patients The regimen indicates a new and important treatment pathway and gives us well-grounded hope for new options for patients with these aggressive breast cancers – and that’s potentially very good news.


  2. [1] Robert C, Long GV, Brady B, et al. Nivolumab in Previously Untreated Melanoma without BRAF Mutation. New England Journal of Medicine [early online publication]. November 16, 2014.
  3. [2] Topalian SL, Sznol M, McDermott DF, et al. Survival, Durable Tumor Remission, and Long-Term Safety in Patients With Advanced Melanoma Receiving Nivolumab. Journal of Clinical Oncology [early online publication]. March 3, 2014. doi: 10.1200/JCO.2013.53.0105.
  4. [3] Study Comparing Opdivo (nivolumab) to Chemotherapy in Treatment Naïve Advanced Melanoma Patients Marks First PD-1 Immune Checkpoint Inhibitor to Demonstrate a Survival Benefit in a Phase 3 Trial [press release]. Bristol-Myers Squibb website. Available at:
  5. Ansell S, Lesokhin A, Borrello I, et al. PD-1 Blockade with Nivolumab in Relapsed or Refractory Hodgkin’s Lymphoma. The New England Journal of Medicine. December 6, 2014DOI: 10.1056/NEJMoa1411087

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