Olaparib in Patients With Metastatic Prostate Cancer With BRCA1/2 Mutation: Results From the TAPUR Study.

PURPOSE: The TAPUR Study is a phase II basket trial that aims to evaluate activity of approved targeted agents in patients with advanced cancers with potentially actionable genomic variants. Data from a cohort of patients with metastatic castrate-resistant prostate cancer (mCRPC) and BRCA1/2 mutations treated with olaparib are reported. METHODS: Eligible patients with measurable mCRPC were matched to treatment according to protocol-specified genomic matching rules. Patients had no remaining standard treatment options, Eastern Cooperative Oncology Group performance status 0-2, and adequate organ function. Simon's two-stage design was used with a primary end point of disease control, defined as objective response or stable disease of at least 16-week duration. Secondary end points include radiographic progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Thirty patients with mCRPC with BRCA1/2 mutations were treated with olaparib. The disease control rate was 69% (95% CI, 51 to 81), and the objective response rate was 58% (95% CI, 37 to 77). The median radiographic progression-free survival and the median overall survival were 38.4 (95% CI, 16.3 to 52.1) weeks and 76.4 (95% CI, 49.3 to 106.0) weeks, respectively. Six of 30 (20%) patients experienced grade 3-4 adverse or serious adverse events including anemia, aspiration, decreased WBC count, and fatigue. CONCLUSION: Olaparib has antitumor activity in patients with mCRPC with BRCA1/2 mutations and warrants further study to determine how to best integrate it into the standard treatment of patients with BRCA1/2-mutated prostate cancer.

Coexistence of Chronic Myelomonocytic Leukemia and Ulcerative Colitis With Rapid Progression to Acute Myelomonocytic Leukemia: A Case Report.

Chronic myelomonocytic leukemia (CMML) is a clonal myeloid neoplasm characterized by sustained peripheral blood monocytosis and variable dyspoiesis. We present a case of a 64-year-old male who presented with severe non-bloody diarrhea, peripheral blood neutrophilia, and monocytosis. He was diagnosed with myeloproliferative CMML type 0 and ulcerative colitis (UC). Next-generation DNA sequencing of a bone marrow sample demonstrated mutations of the TET2, ASXL1, NRAS, and SRSF2 genes along with low-level JAK2^V617F mutation. Both TET2 and SRSF2 mutations are associated with systemic inflammatory and autoimmune disease (SIAD), which includes UC. The patient's UC was managed successfully with vedolizumab infusions. The patient's concurrent CMML was monitored with a "wait and watch" approach. After five months, the patient asymptomatically tested positive for coronavirus disease 2019 (COVID-19). Seven months after his diagnosis of CMML, the patient presented in severe respiratory distress with acute left upper quadrant pain, splenomegaly, and multiorgan failure. A peripheral blood smear demonstrated marked leukocytosis (283 x 10^9 /L) with 39% blasts/promonocytes without Auer rods. The patient was diagnosed with acute myeloid leukemia with myelomonocytic features (AMML). In this report, we discuss the diagnosis of combined CMML and SIAD, mechanisms of immunoregulatory dysfunction that have been suggested to result in CMML progression, and the clinicopathologic significance of the patient's molecular abnormalities.