Miranda Peeples

Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison

PURPOSE Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). METHODS A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naïve and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross-trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. FINDINGS The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. IMPLICATIONS After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV.

Real-World Survival Outcomes and Prognostic Factors Among Patients Receiving First Targeted Therapy for Advanced Renal Cell Carcinoma: A SEER-Medicare Database Analysis

Background The real‐world survival outcomes and prognostic factors among patients receiving first‐line targeted therapy for advanced renal cell carcinoma (aRCC) are not well known. Patients and Methods Adult patients diagnosed with RCC and treated with first‐line targeted therapy were identified from the Surveillance, Epidemiology, and End Results–Medicare database (January 1, 1993 to December 31, 2012). The patients were grouped into early (2006‐2009) or late (2010‐2012) targeted therapy era cohorts by the year of the first‐line targeted therapy initiation. Overall survival (OS) was measured from first‐line targeted therapy initiation and compared between the 2 cohorts using Kaplan‐Meier analyses. The prognostic factors for OS were assessed using a multivariable‐adjusted Cox model. Results A total of 604 and 641 aRCC patients (mean age, 68 years; ˜60% male in both cohorts) initiated first‐line targeted therapy during the early and late targeted therapy eras, respectively. OS was significantly longer in the late than in the early targeted therapy era. Higher tumor grades (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.31‐2.00) and lung (HR, 1.27; 95% CI, 1.06‐1.53), bone (HR, 1.37; 95% CI, 1.13‐1.66), and liver (HR, 1.42; 95% CI, 1.10‐1.84) metastases were associated with significantly shorter OS. Previous nephrectomy (HR, 0.55; 95% CI, 0.42‐0.72) and pazopanib as first‐line targeted therapy relative to sorafenib (HR, 0.56; 95% CI, 0.37‐0.85) or sunitinib (HR, 0.65; 95% CI, 0.44‐0.95) were associated with significantly longer OS. Conclusion The results of these real‐world analyses suggest progress in aRCC management and identified positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bone, or liver metastasis) prognostic factors among patients receiving first‐line targeted therapy. Micro‐Abstract Using the Surveillance, Epidemiology, and End Results–Medicare database, we assessed overall survival (OS) among renal cell carcinoma patients who had initiated first‐line targeted therapy. OS was significantly longer in the late (2010‐2012) versus early (2006‐2009) targeted therapy era. Positive (nephrectomy, pazopanib vs. sunitinib or sorafenib) and negative (higher tumor grade and lung, bong, or liver metastases) OS prognostic factors were identified.

Real-world palbociclib dosing patterns and implications for drug costs in the treatment of HR+/HER2- metastatic breast cancer

ABSTRACT Background: This study described real-world palbociclib dosing patterns and associated impacts on treatment costs for HR+/HER2- metastatic breast cancer (mBC) in the US. Methods: Postmenopausal women with HR+/HER2- mBC who initiated palbociclib-based therapy (initiation date = index date) between 02/03/2015 (palbociclib approval) and 02/29/2016, and continuous quarterly activity 1 year before and 6 months after the index date, were identified in the Symphony Health Solutions database. Rates of 1) dose reduction (≥25 mg dose decrease/daily), and 2) reduction or interruption (>60 day gap in continuous drug supply) were assessed using Kaplan-Meier analyses. Drug wastage cost was estimated based on overlapping days between two prescription fills: the last original dose fill and the first reduced dose fill. Results: 1,242 patients initiated palbociclib-based therapy (mean age = 62.7 years, median follow-up = 8.7 months). During the 12-month post-index period, across the first four lines, dose reduction rates were 31.9–33.7% and dose reduction/interruption rates were 63.5–80.9%. A total of 411 (33.1%) patients changed dose, among whom 128 (31.1%) experienced prescription fill overlap (average = 11.1 days). Mean potential drug wastage cost among patients with fill overlap was

Time on treatment of everolimus and chemotherapy among postmenopausal women with hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative metastatic breast cancer: a retrospective claims study in the US

5,471. Conclusions: Most patients receiving palbociclib experienced dose reduction or interruption early in treatment; the associated drug wastage may lead to considerable costs.

Real-world utilization of molecular diagnostic testing and matched drug therapies in the treatment of metastatic cancers

Abstract Objective: This study aimed to compare time on treatment (TOT) among patients treated with everolimus and chemotherapy, two commonly used treatments for hormone-receptor-positive/human-epidermal-growth-factor-receptor-2-negative (HR+/HER2-) metastatic breast cancer (mBC). Methods: Postmenopausal women with HR+/HER2- mBC who initiated ≥1 new line of therapy for mBC during 20 July 2012–31 March 2014 after a non-steroidal aromatase inhibitor were identified from MarketScan and PharMetrics databases (2002Q1–2014Q2) using a claims-based algorithm. Patients were classified into treatment groups by regimen and line of therapy, and were followed until discontinuation of therapy, end of insurance eligibility, or data cut-off (30 June 2014). Discontinuation was defined as a treatment gap of ≥60 days; patients who did not discontinue were censored at the end of follow-up. TOT was compared between everolimus, chemotherapy, and capecitabine monotherapy using Kaplan–Meier analyses and multivariable Cox models adjusting for line of therapy, age, insurance, de novo mBC diagnosis, prior use of chemotherapy for mBC, sites of metastases, and Charlson comorbidity index. Results: Across the first four lines of therapies for mBC, a total of 940 everolimus, 3410 chemotherapy, and 721 capecitabine monotherapy regimens were included. Based on the different lines of therapies, the median TOT ranged from 5.5 to 7.2 months for everolimus, 4.3 to 4.7 months for chemotherapy, and 3.5 to 6.0 months for capecitabine monotherapy. Pooling all lines of therapies, everolimus was associated with significantly longer TOT compared to chemotherapy (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.62–0.76) or capecitabine monotherapy (multivariable-adjusted HR = 0.73, 95% CI: 0.64–0.83). Longer TOT was consistently observed for everolimus for each line of therapy. Limitations: Proxies used for identifying HR + /HER2- mBC and treatment line, lack of certain clinical factors in claims data, generalizability limited to commercially insured patients in the US. Conclusions: This study found that HR+/HER2- mBC patients receiving everolimus experienced significantly longer TOT than those receiving chemotherapy overall or capecitabine monotherapy.

Patterns of Disease Monitoring and Treatment Among Patients With Tuberous Sclerosis Complex-related Angiomyolipomas

Abstract Aims: To assess the frequency of biopsies and molecular diagnostic testing (human DNA/RNA analysis), anti-cancer drug use (genomically-matched targeted therapy [GMTT], unmatched targeted therapy [UTT], endocrine therapy [ET], and chemotherapy [CT]), and medical service costs among adults with metastatic cancer. Methods: Adults diagnosed with metastatic breast, non-small cell lung (NSCLC), colorectal, head and neck, ovarian, and uterine cancer (2010Q1–2015Q1) were identified in the OptumHealth Care Solutions claims database and followed from first metastatic diagnosis for ≥1 month and until the end of data availability. Utilization was assessed for each cancer cohort (all and patients aged ≥65 years); per-patient-per-month (PPPM) medical service costs were assessed for all patients. Testing frequency estimates were applied to Surveillance, Epidemiology, and End Results Program data to estimate the number of untested patients (2010–2014). Results: Patients with metastatic cancer (n = 8,193; breast [n = 3,414], NSCLC [n = 2,231], colorectal [n = 1,611], head and neck [n = 511], ovarian [n = 275], and uterine [n = 151]) were 63 years old (mean), with 11.1–22.2 months of observation. Biopsy and molecular diagnostic testing frequencies ranged from 7% (uterine) to 73% (ovarian), and from 34% (head and neck) to 52% (breast), respectively. Few were treated with GMTT (breast, 11%; NSCLC, 9%; colorectal, 6%). Treatment with UTT ranged from 0.7% (uterine) to 21% (colorectal). Biopsy, diagnostic testing, and anti-cancer drug therapy were less frequent for those ≥65 years. Medical service costs (PPPM, mean) ranged from

First-line treatment disruption among post-menopausal women with HR+/HER2– metastatic breast cancer: a retrospective US claims study

6,618 (head and neck) to

Treatment patterns and factors associated with the use of everolimus among post-menopausal women with HR+/HER2- metastatic breast cancer: a retrospective US claims study

9,940 (ovarian). The estimated number of untested new patients with metastatic cancer was 636,369 (all) and 341,397 (≥65). Limitations: In addition to the limitations of claims analyses, diagnostic testing frequency may be under-estimated if patients underwent testing prior to study inclusion. Conclusions: The low frequency of molecular diagnostic testing suggests there are opportunities to better inform management of patients with advanced cancer, particularly decisions to treat with GMTT.

Epilepsy treatment patterns among patients with tuberous sclerosis complex

OBJECTIVE To use the tuberous sclerosis complex (TSC) Natural History Database to describe monitoring and treatment patterns among patients with TSC-related angiomyolipomas (AMLs). METHODS This study used the TSC Natural History Database, which contains demographics, affected areas, diagnosis, and treatments for more than 1300 patients with TSC enrolled in 16 participating clinics during 2006-2013. Patient characteristics, AML monitoring tests, and AML treatments were assessed. RESULTS Among the 621 patients with TSC-related AMLs, 54% were female; 77% were Caucasian. Median age at TSC diagnosis was <1 year, whereas median age at AML diagnosis was 9.8 years. Most patients (84%) had at least 1 monitoring test following AML diagnosis. The most commonly used tests were magnetic resonance imaging (MRI; 65% of patients), ultrasound (62%), and computed tomography (41%). Between 2000 and 2012, MRI made up an increasingly large proportion of the total number of monitoring tests. Once diagnosed, 155 (25%) of patients received treatment for AML. The median time from diagnosis to first treatment was 3.8 years. The most common treatments were embolization (10%), everolimus (9%), sirolimus (6%), and nephrectomy (6%). The rate of nephrectomies declined over time, with none conducted during 2011 and 2012. No subsequent surgeries were reported among the 71 patients who received mTOR inhibitor as first-line therapy. CONCLUSION The use of MRIs increased between 2000 and 2012 among patients with TSC-AML. The majority of these patients did not receive treatment for AML. Use of nephrectomy decreased over the study period and was particularly rare in patients who received an mTOR inhibitor.

Comparison of medical costs and healthcare resource utilization of post-menopausal women with HR+/HER2- metastatic breast cancer receiving everolimus-based therapy or chemotherapy: a retrospective claims database analysis.

Abstract Objective: This study assessed disruption of first-line treatments initiated after the approval of the first CDK 4/6 inhibitor, palbociclib, among post-menopausal women with HR+/HER2– metastatic breast cancer (mBC) in the US. Methods: Post-menopausal women with HR+/HER2– mBC who initiated first-line endocrine therapy or chemotherapy (index therapy) between February 3, 2015 (palbociclib approval date) and February 29, 2016 (end of data) were identified from the Symphony Source Lx database. Patients were required to have continuous quarterly activity (defined as ≥1 pharmacy or medical claim) for 12 months prior to and 1 month after the initiation of the index therapy (index date). Treatment disruption was defined as a treatment gap of ≥60 days or adding an agent after the original therapy. Kaplan-Meier analyses were conducted to estimate treatment disruption rates during the 6 months following the index date. Patients without treatment disruption were censored at the end of continuous quarterly activity or end of data. Results: A total of 8,160 and 2,153 eligible patients initiated endocrine therapy or chemotherapy as their first-line mBC treatment, with a median follow-up of 6.7 and 7.6 months, respectively. The three most prevalent metastatic sites were bone (28.1–42.2%), liver (8.8–17.3%), and lung (8.6–9.5%). Overall, 37.7% (n = 3,074) of patients receiving endocrine therapy and 86.1% (n = 1,852) of patients receiving chemotherapy encountered treatment disruption at 6 months (log-rank test p < .05). Conclusions: Treatment disruption rates of first-line therapies were sub-optimal among post-menopausal women with HR+/HER2– mBC, primarily driven by chemotherapy users. New therapies or interventions are needed to reduce treatment disruption in this patient population.