Abstract 5236: Complete response to selpercatinib (LOXO-292), a highly selective RET inhibitor, in a patient with <i>RET</i> fusion-positive breast cancer
Authors: Masayuki Takeda, Satomi Watanabe, S. Michael Rothenberg, Jennifer Kherani, Pearl P. French, Elizabeth Olek
Journal: Cancer Research (2020)

Abstract Background: Activating RET gene fusions have been reported in diverse solid tumors but &amp;lt;0.1% of breast cancers. Selpercatinib (LOXO-292), an investigational, highly selective and potent small molecule RET kinase inhibitor, has demonstrated significant anti-tumor activity in diverse RET fusion-positive solid tumor patients in an ongoing clinical trial (LIBRETTO-001, NCT03157128). Here we describe the first patient with RET fusion-positive breast cancer treated with selpercatinib. Case summary: A 46-year-old Japanese woman presented with FDG-avid right axillary, right neck and mediastinal lymphadenopathy on PET-CT imaging. Ultrasound identified a hypoechoic nodule in the right breast; biopsy revealed malignant cells, ER(+), PgR(-), and HER2(-). She was diagnosed with stage IV adenocarcinoma of the right breast. Genomic testing results of a lymph node specimen identified a CCDC6-RET fusion with no other reported alterations, including none in BRCA1 or BRCA2. Consistent with local standard of care, she received treatment with tamoxifen plus goserelin from March through June 2019, but these were discontinued for progression in the right breast and new lesions in the left lower lung. Re-biopsy revealed that the molecular biology changed into triple-negative at the time of progression. On 10-Jul-19 she started treatment with selpercatinib at the recommended Phase 2 dose of 160 mg twice daily in the ongoing Phase 1/2 trial of selpercatinib. She experienced rapid clinical improvement, with resolution of right breast and neck pain and erythema. Spiral CT imaging on 31-Jul-2019 and 4-Sep-2019 demonstrated a partial response by RECIST 1.1 (tumor reductions -30% and -30%), with reduction in multiple right breast masses, axillary, neck and mediastinal lymphadenopathy and left lung metastases; repeat imaging on 30-Oct-19 demonstrated a complete response. At the time of this writing, she remains in response and on treatment for &amp;gt;150 days, with all adverse events grades 1-2, and most recovered and none requiring dose interruption or modification. Conclusion: Selpercatinib demonstrated anti-tumor activity in a patient with RET fusion-positive breast cancer. To our knowledge, this is the first report of a breast cancer patient with a sustained response to selective, RET-targeted therapy and adds to the diversity of RET fusion-positive tumor types that may benefit from selective RET inhibition. Citation Format: Masayuki Takeda, Satomi Watanabe, S. Michael Rothenberg, Jennifer Kherani, Pearl P. French, Elizabeth Olek. Complete response to selpercatinib (LOXO-292), a highly selective RET inhibitor, in a patient with RET fusion-positive breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5236.