A randomized phase II trial of everolimus and letrozole or hormonal therapy in women with advanced, persistent or recurrent endometrial carcinoma: A GOG Foundation study.

BACKGROUND: Blocking the PI3K/AKT/mTOR pathway decreases resistance to hormonal therapy in endometrial carcinoma (EC). OBJECTIVE: In this study, the aim was to assess the efficacy and tolerability of everolimus(E)/letrozole (L) or medroxyprogesterone acetate(M)/tamoxifen(T) in the treatment of metastatic EC. STUDY DESIGN: This single stage, open-label two arm randomized phase II trial accrued women with advanced/persistent/recurrent EC. Treatment with E (10 mg daily) and L (2.5 mg daily) or T (20 mg twice daily) and M (200 mg daily alternating weeks) was randomly assigned, and stratified by prior adjuvant therapy. Treatments were administered orally. Primary endpoint was response rate. RESULTS: Between February 2015 and April 2016, everolimus/letrozole (n = 37) or MT (n = 37) was assigned to 74 patients. Median follow-up was 37 months. Eight (22%; 95% CI 11% to 37%) patients responded on EL (one CR) and nine (25%; 95% CI 14% to 41%) patients responded on MT (three CRs). Median PFS for EL and MT arms was 6 months and 4 months, respectively. On EL, chemo-nave patients demonstrated a 28 month median PFS; prior chemotherapy patients had a 4-month median PFS. On MT, patients without prior therapy had a 5-month median PFS; those with prior chemotherapy demonstrated a 3-month PFS. Common grade 3 adverse events were anemia (9 [24%] patients EL vs 2 [6%] MT) and mucositis (2 [5%] vs 0 [0%]). Grade 3/4 thromboembolic events were observed with MT but not with EL (0 [0%] vs 4 [11%]). CONCLUSIONS: EL and MT demonstrated clinically meaningful efficacy in recurrent EC patients. The higher PFS observed in chemo-naïve patients is worthy of confirmation in future studies.

A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS).

OBJECTIVE: Up to 87% of uterine leiomyosarcomas have estrogen receptor positivity. There are no effective adjuvant therapies for LMS. The objective of this study was to determine the efficacy of letrozole in patients with newly diagnosed uterine leiomyosarcoma (uLMS). The primary endpoint of this study was a reduction in the recurrence rate for patients with this disease. METHODS: We performed a randomized, open-label, phase II study of letrozole (experimental arm) administered orally on a daily basis vs. observation (control) in patients with newly diagnosed early stage uLMS. Patient enrollment was to be open to any individual with newly diagnosed uLMS seen in the Gynecologic Oncology Center at M. D. Anderson Cancer Center. Hormone receptor positivity using CLIA approved lab testing was an eligibility requirement. No prior therapy was allowed. RESULTS: Nine patients were randomized. Four patients were in the experimental arm and five patients were in the observation arm. No patients had prior therapy. The median duration of protocol treatment was 43.9 months (range, 6.5-70.2). The median PFS for the experimental arm was not reached (NR) compared to 17.3 months. The percent progression free at 12 and 24 months was 100% for patients receiving letrozole compared to 80% at 12 months and 40% at 24 months for patients in the observation arm. CONCLUSIONS: While no definitive conclusions can be made due to early study closure, these early observations warrant further investigation. We desperately need an effective adjuvant therapy for women with early stage uLMS.

Association Between 2 Measures of Cognitive Instrumental Activities of Daily Living and Their Relation to the Montreal Cognitive Assessment in Persons With Stroke.

OBJECTIVES: To explore the relation between a computer adaptive functional cognitive questionnaire and a performance-based measure of cognitive instrumental activities of daily living (C-IADL) and to determine whether the Montreal Cognitive Assessment (MoCA) at admission can identify those with C-IADL difficulties at discharge. DESIGN: Prospective cohort study. SETTING: Acute inpatient rehabilitation unit of an academic medical center. PARTICIPANTS: Inpatients (N=148) with a diagnosis of stroke (mean age, 68y; median, 13d poststroke) who had mild cognitive and neurological deficits. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Admission cognitive status was assessed by the MoCA. C-IADL at discharge was assessed by the Executive Function Performance Test (EFPT) bill paying task and Activity Measure of Post-Acute Care (AM-PAC) Applied Cognition scale. RESULTS: Greater cognitive impairment on the MoCA was associated with more assistance on the EFPT bill paying task (ρ=-.63; P<.01) and AM-PAC Applied Cognition scale (ρ=-.43; P<.01). This relation was nonsignificant for higher MoCA scores and EFPT bill paying task scores. The AM-PAC Applied Cognition scale and the EFPT bill paying task had low agreement in classifying functional performance (Cohen's κ=.20). A receiver operating characteristic curve identified optimal MoCA cutoff scores of 20 and 21 for classifying EFPT bill paying task status and AM-PAC Applied Cognition scale status, respectively. For values above 20 and 21, sensitivity increased whereas specificity decreased for classifying functional deficits. Approximately one third of the participants demonstrated C-IADL deficits on at least 1 C-IADL measure at discharge despite having a MoCA score of ≥26 at admission. CONCLUSIONS: Questionnaire and performance-based methods of assessment appear to yield different estimates of C-IADL. Low MoCA scores (<20) are more likely to identify those with C-IADL deficits on the EFPT bill paying task. The results suggest that C-IADL should be assessed in those who have mild or no cognitive difficulties at admission.