Single-agent anti-PD-1 or combined with ipilimumab in patients with mucosal melanoma: an international, retrospective, cohort study.

BACKGROUND: Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology and poor prognosis. Data on the efficacy of immune checkpoint inhibitors (ICIs) are limited. We determined the efficacy of ICIs in MM, analyzed by primary site and ethnicity/race. PATIENTS AND METHODS: A retrospective cohort study from 25 cancer centers in Australia, Europe, USA and Asia was carried out. Patients with histologically confirmed MM were treated with anti-programmed cell death protein 1 (PD-1) ± ipilimumab. Primary endpoints were response rate (RR), progression-free survival (PFS), overall survival (OS) by primary site (naso-oral, urogenital, anorectal, other), ethnicity/race (Caucasian, Asian, Other) and treatment. Univariate and multivariate Cox proportional hazards model analyses were conducted. RESULTS: In total, 545 patients were included: 331 (63%) Caucasian, 176 (33%) Asian and 20 (4%) Other. Primary sites included 113 (21%) anorectal, 178 (32%) urogenital, 206 (38%) naso-oral and 45 (8%) other. Three hundred and forty-eight (64%) patients received anti-PD-1 and 197 (36%) anti-PD-1/ipilimumab. RR, PFS and OS did not differ by primary site, ethnicity/race or treatment. RR for naso-oral was numerically higher for anti-PD-1/ipilimumab [40%, 95% confidence interval (CI) 29% to 54%] compared with anti-PD-1 (29%, 95% CI 21% to 37%). Thirty-five percent of patients who initially responded progressed. The median duration of response (mDoR) was 26 months (95% CI 18 months-not reached). Factors associated with short PFS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3 (P < 0.01), lactate dehydrogenase (LDH) more than the upper limit of normal (ULN) (P = 0.01), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). Factors associated with short OS were ECOG PS ≥1 (P < 0.01), LDH >ULN (P = 0.03), lung metastases (P < 0.01) and ≥1 previous treatments (P < 0.01). CONCLUSIONS: MM has poor prognosis. Treatment efficacy of anti-PD-1 ± ipilimumab was similar and did not differ by ethnicity/race. Naso-oral primaries had numerically higher response to anti-PD-1/ipilimumab, without difference in survival. The addition of ipilimumab did not show greater benefit over anti-PD-1 for other primary sites. In responders, mDoR was short and acquired resistance was common. Other factors, including site and number of metastases, were associated with survival.

Emergency contraception update: a Canadian perspective.

Barriers to hormonal emergency contraceptive (EC) access in Canada and the United States led professional and lay groups to lobby for levonorgestrel (LNG) (PLAN B, Barr Pharmaceuticals, Pomona, New York) to be made available over-the-counter. In December 2000, British Columbia, Canada, granted EC prescriptive authority to pharmacists, followed by Quebec in December 2001 and Saskatchewan in September 2003. In April 2005, Health Canada placed LNG on non-prescription, behind-the-pharmacy-counter status with no age restriction. After much controversy, in August 2006, the Food and Drug Administration (FDA) approved over-the-counter access to LNG by adults in the United States. Results of our experience in Canada and recent information regarding mechanisms of action, effectiveness, adverse effects, and the effect of increased availability on reproductive health outcomes are presented here to help inform clinical practice.

Assessment of an adverse drug reaction monitoring program in nursing homes.

An adverse drug reaction monitoring program was developed in ten geriatric nursing care facilities with a population of 826 patients. Over a two year period, the incidence of moderate to severe adverse reactions was decreased from 27 to 20 percent. Digitalis glycosides, antipsychotics, sedatives and hypnotics, diuretics, and anti-inflammatory agents were responsible for more than three quarters of the reactions. Elderly females receiving large numbers of drugs and patients having a history of a previous reaction were found to be at high risk of experiencing an adverse effect. A substantial reduction in the number of drug-related acute care hospital admissions and a decrease in drug consumption demonstrated the cost effectiveness of the program. The response of other health care professionals to the program was excellent. A Patient Assessment Form was developed to assist in the quarterly review of patient medications. Guidelines for monitoring adverse drug reactions in nursing care facilities are suggested to aid other pharmacists in the implementation of similar clinical services.

Developing an adverse drug reaction program in nursing homes.

The study of 826 geriatric nursing home patients was undertaken by a pharmacist to determine the incidence of adverse reactions to drugs. A formalized adverse drug reaction reporting program was used as the basis for the detection of unwanted drug effects. Approximately 27% of patients experienced a moderate to severe adverse effect. Five groups of drugs accounted for three-quarters of the reactions detected. The majority of these reactions were predictable and preventable. Females over the age of 70 on large quantities of drugs were significantly more susceptible to experiencing an adverse reaction. Physicians implemented 76% of pharmacist initiated recommendations for the treatment of adverse effects and were appreciative of increased pharmacy involvement. The implementation of such recommendations was felt to have substantially reduced the incidence of drug-induced acute hospitalizations. Although the information was generated in nursing homes, it may be generalized to other geriatric specialty areas such as medical wards and extended care units. Several recommendations are provided on how other pharmacists can implement similar clinical services in their areas of professional practice.