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AACR Annual Meeting 2020 Highlights: Potential New Treatment Options for Patients with High-Risk Breast Cancers

Researchers present findings on PARP inhibitors and novel immunotherapy combinations at the first of two virtual AACR conferences
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The annual American Association for Cancer Research (AACR) meeting is the largest international cancer conference, attracting more than 25,000 participants every spring. Scientists and physicians from every cancer research discipline join representatives from the pharmaceutical industry, government, patient advocacy organizations, and public and private funders of research.

This year, AACR's annual meeting went virtual this year and was also split into two sessions. Part I (April 27-28) focused on updates from clinical trials. Part II will be held June 22-24 and include presentations on the latest developments in tumor biology and genetics, precision oncology, early detection, and immunotherapies.

Highlights from the first session:

I-SPY2 Trial: Immunotherapy/PARP Inhibitor/Chemotherapy Combination Shows Promising Results​

Reporting for the I-SPY 2 clinical trial group, BCRF investigator Dr. Lajos Pusztai shared data from a trial testing the combination of immunotherapy plus a PARP inhibitor with chemotherapy in patients with HER2-negative breast cancer. In all breast cancer subgroups tested, the combination improved pathological complete response (pCR)—no presence of invasive tumor in the breast or lymph nodes at time of surgery—from 20 percent with chemotherapy alone to 37 percent with the combination.

In patients with triple-negative breast cancer (TNBC), the combination improved pCR from 27 percent with chemotherapy alone to 47 percent with the combination. Patients with hormone receptor-positive breast cancer also benefitted, with a pCR of 28 percent, up from 14 percent with chemotherapy alone.

Patients were randomized to receive standard neoadjuvant (pre-surgical) chemotherapy, or chemotherapy plus the immunotherapy drug durvalumab (Imfinzi®), a PD-L1 inhibitor, and olaparib (Lynparza®), a PARP inhibitor approved for breast, ovarian, and other cancers caused by inherited BRCA mutation. The study results demonstrate that the durvalumab/olaparib/chemotherapy combination is likely to be superior to chemotherapy alone, and researchers will move to the next phase of clinical trial testing. Read more about the study here. The I-SPY 2 trial is supported in part by BCRF.

IMPRIME 1 Trial: Checkpoint Inhibitor/Immunotherapy Combination May Benefit Some Patients with Advanced TNBC

Pembrolizumab (Keytruda®) is another checkpoint (PD-L1) inhibitor. When administered in combination with chemotherapy, PD-L1 inhibitors have been shown to produce a durable response in some patients with advanced TNBC. When used as single agents, however, they have provided limited benefit for most patients. The Phase II IMPRIME 1 study tested the combination of pembrolizumab with an experimental immune-activating drug called Imprime PGG in patients with metastatic TNBC that has progressed on other drugs. In this safety study of 44 patients, the combination of Imprime PGG and pembrolizumab nearly doubled progression-free survival compared to what was reported with pembrolizumab alone in the KEYNOTE-086 study. Of note, a small subset of patients whose primary breast cancer had been estrogen receptor-positive but changed to TNBC in metastasis did extremely well, with 50 percent showing stable disease for more than six months and a median overall survival of 17 months.

EMBRACA Study: Final Analysis of PARP Inhibitor Benefit Inconclusive

The Phase III EMBRACA study compared the PARP inhibitor talazoparib (Talzenna®) with chemotherapy in patients with advanced HER2-negative breast cancer and a germline (inherited) mutation in the BRCA1 or BRCA2 genes. In previous analysis, the investigators reported that talazoparib significantly prolonged progression-free survival compared to chemotherapy from 5.6 months to 8.6 months, which led the FDA to approve talazoparib.

However, in a final analysis reported at the AACR meeting, they did not see a significant improvement in overall survival with talazoparib compared to chemotherapy. The study authors noted that more than half of patients receiving chemotherapy went on to receive the PARP inhibitor. This, they said, may have caused an underestimation of the benefit of the talazoparib. Additionally, patients receiving talazoparib reported better quality of life and less severe side effects than those on chemotherapy. Further analyses are ongoing. Results of the study suggest that talazoparib may be an effective alternative to chemotherapy for this group of patients. Read more about the study here.

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