Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

BACKGROUND: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status. MATERIALS AND METHODS: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA). All patients were treated with neoadjuvant trastuzumab (n = 765) in combination with pertuzumab (n = 328), lapatinib (n = 187) or without a second anti-HER2 drug (n = 250). Event-free survival (EFS) and overall survival (OS) outcomes were available in a combined series of 268 patients (i.e. NEOHER and PAMELA) with a pCR (n = 118) and without a pCR (n = 150). Cox models were adjusted to evaluate whether HER2DX can identify patients with low or high risk beyond pCR status. RESULTS: HER2DX pCR score was significantly associated with pCR in all patients [odds ratio (OR) per 10-unit increase = 1.59, 95% confidence interval 1.43-1.77; area under the ROC curve = 0.75], with or without dual HER2 blockade. A statistically significant increase in pCR rate due to dual HER2 blockade over trastuzumab-only was observed in HER2DX pCR-high tumors treated with chemotherapy (OR = 2.36 (1.09-5.42). A statistically significant increase in pCR rate due to multi-agent chemotherapy over a single taxane was observed in HER2DX pCR-medium tumors treated with dual HER2 blockade (OR = 3.11, 1.54-6.49). The pCR rates in HER2DX pCR-low tumors were ≤30.0% regardless of treatment administered. After adjusting by pCR status, patients identified as HER2DX low-risk had better EFS (P < 0.001) and OS (P = 0.006) compared with patients with HER2DX high-risk. CONCLUSIONS: HER2DX pCR score and risk score might help identify ideal candidates to receive neoadjuvant dual HER2 blockade in combination with a single taxane in early-stage HER2+ breast cancer.

Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors.

BACKGROUND: To establish the maximum tolerated dose, determine safety/tolerability and evaluate the pharmacokinetics and preliminary efficacy of olaparib in combination with cisplatin in patients with advanced solid tumors. PATIENTS AND METHODS: Patients aged ≥ 18 years with advanced solid tumors, who had progressed on standard treatment, were assigned to a treatment cohort and received oral olaparib [50-200 mg twice daily (bid); 21-day cycle] continuously or intermittently (days 1-5 or 1-10) in combination with cisplatin (60-75 mg/m(2) intravenously) on day 1 of each cycle. RESULTS: Dose-limiting toxicities (DLTs) of grade 3 neutropenia (cisplatin 75 mg/m(2) with continuous olaparib 100 mg bid or 200 mg bid; n = 1 each) and grade 3 lipase elevation (cisplatin 75 mg/m(2) with olaparib 100 mg bid days 1-10 or 50 mg bid days 1-5; n = 1 each) were reported. Olaparib and cisplatin doses were subsequently reduced to 50 mg bid days 1-5 and 60 mg/m(2), respectively; no DLTs were reported for patients receiving this regimen. The most frequent grade ≥ 3 adverse events were neutropenia (16.7%), anemia (9.3%) and leucopenia (9.3%). Thirty patients (55.6%) received colony-stimulating factors for hematologic support. The overall objective response rate was 41% for patients with measurable disease, and 43% and 71% among patients with a BRCA1/2 mutation who had ovarian and breast cancer, respectively. CONCLUSIONS: Olaparib in combination with cisplatin 75 mg/m(2) was not considered tolerable; intermittent olaparib (50 mg bid, days 1-5) with cisplatin 60 mg/m(2) improved tolerability. Promising antitumor activity in patients with germline BRCA1/2 mutations was observed and warrants further investigation.

Accuracy of the health information system on malaria surveillance in Vietnam.

The health information system (HIS) is a key component of control programs and its accuracy is necessary for the assessment of disease risks, the formulation of priorities and the evaluation of the cost-effectiveness of different interventions. In order to assess the quality of the HIS in estimating malaria morbidity in Vietnam, we compared data obtained by a 2-year active (ACD) and passive case detection (PCD) study with those routinely collected at the local commune health centres (CHC) at three sites having different malaria epidemiology. The majority of malaria cases (80-95%) detected by ACD were missed by the HIS. Similarly, most malaria cases (50-90%) detected by PCD were also missed by the HIS, and this was proportional to the number of active private practitioners. Reasons for this low sensitivity are low CHC attendance, high attendance at private health facilities, widespread self-medication and attendance at central health facilities. In conclusion, although malaria has sharply decreased in Vietnam over the past 10 years, the current HIS greatly underestimates the malaria burden. Involvement of the private sector and the establishment of sentinel sites might improve the quality of data and the relevance of HIS in malaria control.

Malaria epidemiology in a rural area of the Mekong Delta: a prospective community-based study.

Over the past 10 years, the Mekong Delta region in Vietnam has experienced fast socio-economic development with subsequent changes in malaria vectors ecology. We conducted a 2-year prospective community-based study in a coastal rural area in the southern Mekong Delta to re-assess the malaria epidemiological situation and the dynamics of transmission. The incidence rate of clinical malaria, established on 558 individuals followed for 23 months by active case detection and biannual cross-sectional surveys, was 2.6/100 person-years. Over the 2-year study period, the parasite rate and malaria seroprevalence (Plasmodium falciparum and P. vivax) decreased significantly from 2.4% to almost 0%. Passive case detection (PCD) of clinical cases and serological follow-up of newborns carried out in a larger population confirmed the low and decreasing trend of malaria transmission. The majority of fever cases were seen in the private sector and most were unnecessarily treated with antimalarials. Training and involvement of the private sector in detection of malaria cases would greatly improve the quality of health care and health information system.

Acute myelogenous leukemia: current treatment and future directions.

Acute myelogenous leukemia (AML), although an uncommon disorder, is a useful prototype for the treatment of malignancies in general. Significant advances have been made in both the understanding and treatment of this disease. In particular, clinically relevant molecular mechanisms of disease in AML are being defined that hold future therapeutic promise. We review the classification and biology of AML and the current treatment controversies in the use of chemotherapy and bone marrow transplantation, and suggest directions for future research.