Pembrolizumab activity in patients with Fanconi anemia repair pathway competent and deficient tumors.

BACKGROUND: Given the observed antitumor activity of immune-checkpoint-inhibitors in patients with mismatch-repair deficient (MSI-H) tumors, we hypothesized that deficiency in homologous-recombination-repair (HRR) can also influence susceptibility. METHODS: Patients with disease progression on standard of care and for whom pembrolizumab had no FDA approved indication received pembrolizumab. Patients with MSI-H tumors were excluded. Objectives included immune-related objective response rate (iORR), progression-free survival (PFS) and 20-weeks-PFS. Pembrolizumab was given every 3 weeks and scans performed every six. We evaluated a triple-stain (FANCD2foci/DAPI/Ki67) functional assay of the Fanconi Anemia (FA) pathway: FATSI, in treated patients' archived tumors. The two-stage sample size of 20/39 patients evaluated an expected iORR≥20% in the whole population vs. the null hypothesis of an iORR≤5%, based on an assumed iORR≥40% in patients with functional FA deficiency, and < 10% in patients with intact HRR. An expansion cohort of MSI stable endometrial cancer (MS-EC) followed. Exploratory stool microbiome analyses in selected patients were performed. RESULTS: Fifty-two patients (45F,7M;50-evaluable) were enrolled. For the 39 in the two-stage cohort, response evaluation showed 2CR,5PR,11SD,21PD (iORR-18%). FATSI tumor analyses showed 29 competent (+) and 10 deficient (-). 2PR,9SD,17PD,1NE occurred among the FATSI+ (iORR-7%) and 2CR,3PR,2SD,3PD among the FATSI(-) patients (iORR-50%). mPFS and 20w-PFS were 43 days and 21% in FATSI+, versus 202 days and 70% in FATSI(-) patients. One PR occurred in the MS-EC expansion cohort. CONCLUSIONS: Pembrolizumab has meaningful antitumor activity in malignancies with no current FDA approved indications and FA functional deficiency. The results support further evaluation of FATSI as a discriminatory biomarker for population-selected studies.

Activity of combination chemotherapy, docetaxel and epirubicin as neoadjuvant therapy for women with breast cancer.

BACKGROUND: This study assesses the efficacy of epirubicin and docetaxel as neoadjuvant therapy for women with breast cancer. PATIENTS AND METHODS: This is a single institution, single arm, phase II study of epirubicin given at 75 mg/m(2) and docetaxel at 75 mg/m(2) every three weeks for four cycles prior to surgical excision in women with large breast cancers. Pegfilgrastim was routinely administered as primary prophylaxis against febrile neutropenia. RESULTS: Out of the 18 patients enrolled on the study, 12 (66.7%) had a clinical response and 13 (72.2%) had a pathologic response, with a pathologic complete response of 5.6%. Pre-menopausal women and patients with estrogen receptor positive tumors had a higher response rate. One patient died due to sepsis and febrile neutropenia. CONCLUSION: Combination chemotherapy with epirubicin and docetaxel is highly active against breast cancer. With close monitoring for toxicity, this combination can be safely administered with mild side-effects.

Coronary artery bypass grafting surgery in Oklahoma: processes and outcomes of care.

Coronary artery bypass grafting (CABG) is a commonly performed operation on Oklahoma Medicare beneficiaries. In 1994, the Centers for Medicare & Medicaid Services funded a project to evaluate process-oriented quality improvement activities for this surgery. Structured medical record review was performed on the charts of 2,312 Oklahoma Medicare patients who had a CABG surgery between July 1, 1995, and June 30, 1996, and on 926 patients who had their surgery from July 1 through December 31, 1998. Demographic, procedural and outcome variables were abstracted from each medical record. In addition to summarizing the clinical and demographic characteristics, we evaluated inter-hospital variations in both processes and outcomes of care. Significant variations in care were demonstrated for the 13 Oklahoma hospitals in which this operation was performed. The results of this project suggest that there are substantial opportunities to improve the quality of care for CABG in Oklahoma.

Screening mammography for Oklahoma Medicare beneficiaries: a national priority for quality improvement.

Breast cancer is one of the most common malignancies diagnosed in women in the United States. It is estimated that more than 2,700 new cases of female breast cancer will be diagnosed in Oklahoma this year. Using the Medicare mammography denominator file and Medicare claims data (October 1999 through September 2001), we assessed the utilization of mammography for this population. The overall biennial mammography rate for Oklahoma Medicare patients was 46.9% (95% CI 46.7-47.1) and was 54.7% (95% CI 54.3-55.2) for Medicare patients aged 50-67 years. There were significant racial disparities in utilization of mammography. In addition, there was substantial county-to-county variation in the utilization of mammography in Oklahoma. When compared to other states and territories, Oklahoma mammography rates for this population were in the lowest quartile nationally, ranking 47th in the nation. Increasing the use of mammography services for Medicare patients is a national priority for healthcare quality improvement.