Impact of Polypharmacy Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Older Adults.

Polypharmacy is common in older adults with cancer, but there is little evidence evaluating the impact of polypharmacy and other medication hazards on allogeneic hematopoietic cell transplantation (alloHCT) outcomes. A small number of prior studies have evaluated the impact of potentially inappropriate medication (PIM) use in the setting of alloHCT, with mixed results. We evaluated the effects of pre-alloHCT polypharmacy, PIM use, and drug-drug interactions (DDIs) on post-alloHCT outcomes, including overall survival (OS), progression-free survival (PFS), non-relapse mortality (NRM), hospital length of stay (LOS), number of non-hematologic grade ≥3 adverse events (AEs) within 100 days after alloHCT, and number of readmissions within the first 100 days after alloHCT. The study population was a single-center prospective cohort of 148 patients ≥ 50 years of age. Pre-alloHCT medication lists were retrospectively collected from the electronic medical record, including both scheduled and as-needed medications. PIMs were defined by a modified 2019 American Geriatrics Society Beers Criteria. DDIs were analyzed using Lexi-Interact. Polypharmacy was common in this population; the median number of medications was seven (range, 0 to 23). Fifty-two patients (35%) were prescribed nine or more medications, and 73 patients (49%) had at least one PIM prescribed. The median number of DDIs was three (range, 0 to 31), and the most common severity was major (48%). After adjusting for age and Hematopoietic Cell Transplant Comorbidity Index (HCTCI), both the number of all medications and number of scheduled medications were associated with inferior OS, with hazard ratios (HRs) of 1.07 (95% confidence interval [CI], 1.01 to 1.12; P = .02) and 1.08 (95% CI, 1.00 to 1.15; P = .04), respectively. Receipt of nine or more scheduled medications was associated with inferior OS (HR, 1.92; 95% CI, 1.11 to 3.32; P = .02). The number of PIMs was also significantly associated with OS (HR, 1.24; 95% CI, 1.00 to 1.54, P = .05). After adjusting for age, HCTCI, and total number of medications, a greater number of DDIs were significantly associated with longer hospital length of stay (difference, 0.74 days; 95% CI, 0.09 to 1.40, P = .03). In adjusted analyses, there were no significant polypharmacy-related predictors of NRM, LOS, or non-hematologic grade ≥3 AEs. These data demonstrate the utility of pre-alloHCT polypharmacy, PIM use, and DDIs as important prognostic factors and support routine pre-alloHCT medication review by physicians and pharmacists with a goal of appropriate de-prescribing where possible.

Cost-effectiveness of ribociclib plus endocrine therapy versus placebo plus endocrine therapy in HR-positive, HER2-negative breast cancer.

BACKGROUND: The 2015 American Society of Clinical Oncology guidelines recommend first-line treatment of hormone receptor (HR)-positive breast cancer with endocrine therapy plus or minus palbociclib, a selective cyclin-dependent kinase (CDK)4/6 inhibitor. In 2018, the U.S. Food and Drug Administration approved ribociclib, a new orally available selective CDK4/6 inhibitor. While gains in progression-free survival (PFS) and overall survival (OS) from ribociclib are important for clinical and treatment outcomes, trade-offs in adverse events (AEs) and additional costs necessitate cost-effectiveness analysis (CEA) to assist consideration by third-party payer systems, physicians, and patients. OBJECTIVES: To (a) develop a Markov model and (b) determine the cost-effectiveness of ribociclib plus endocrine therapy versus endocrine therapy alone as treatment for premenopausal and perimenopausal patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A lifetime 3-state Markov model ("stable," "progressed," and "dead" health states) was developed using a U.S. payer perspective. Transition probabilities were calculated based on OS and PFS outcomes from the randomized controlled phase 3 trial MONALEESA-7. These Kaplan-Meier curves were extended to lifetime by estimating best-fit distributions using loglogistic distribution for ribociclib curves and Weibull distribution for placebo curves. Costs were obtained from national data sources using 2019 U.S. dollars (USD) and discounted by 3%. Utilities were obtained via published breast cancer literature and were included for each health state and for time spent with each AE. Results were expressed as an incremental cost-effectiveness ratio (ICER) expressed as USD per quality-adjusted life-year (QALY) saved. Treatments were assumed to be cost-effective based on a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Base-case, 1-way sensitivity tornado diagrams and probabilistic sensitivity analyses demonstrated changes in the ICER and were driven by the cost of ribociclib and the utility of remaining in the stable health state. RESULTS: Ribociclib plus endocrine therapy was cost-effective at an ICER of $124,513 per QALY when compared with endocrine therapy alone at a WTP threshold of $150,000. The ribociclib plus endocrine therapy arm had an effectiveness of 5.28 QALYs and a total cost of $385,112, while placebo plus endocrine therapy provided only 2.46 QALYs at a lower total cost of $67.246. The model was sensitive to the cost of ribociclib and the utility of time spent in the stable health state. Probabilistic sensitivity analysis demonstrated that endocrine therapy alone was cost-effective until a WTP of $125,000 and was cost-effective 72% of the time at the WTP threshold. CONCLUSIONS: Ribociclib plus endocrine therapy is more cost-effective than endocrine therapy alone. Professionals in managed care settings should consider the pharmacoeconomic benefits of ribociclib for the treatment of HR-positive, HER2-negative breast cancer as they make value-based formulary decisions. Further CEAs should be considered as direct treatment comparison trials between CDK4/6 inhibitors are completed in the future. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.