Real-world evidence in lung and hematologic oncology health technology appraisals: a review of six assessment agencies.

Aim: To assess the use and acceptability of real-world evidence (RWE) in lung and hematologic cancer appraisals. Materials & methods: A review of appraisals published by National Institute for Health and Care Excellence (NICE) in the UK was conducted. A total of 20 case studies employing RWE were identified and compared across five additional health technology assessment agencies: Scottish Medicines Consortium (SMC) (Scotland), CADTH (Canada), INESSS (Quebec), HAS (France) and IQWiG (Germany). Results: Of 80 RWE references from 20 case studies from NICE, 67 were identified in the respective CADTH submissions, 46 in IQWiG, 37 in INESSS, 37 in HAS, and 33 in SMC. NICE had the highest RWE acceptance rate (90%), followed by HAS (88%), SMC (82%), INESSS (73%), IQWiG (68%) and CADTH (67%). Conclusion: RWE was generally accepted by respective committees, allowing improved access to innovative treatments.

Use of real-world evidence for assessing the value of cancer treatments Health technology assessment (HTA) is a process used to decide whether a drug works well enough to be worth paying for. Most drugs have data showing how well they work from special studies called clinical trials. Sometimes a manufacturer also has evidence of a drug or disease that is not from a clinical trial but from the real world. This review discusses how real-world evidence (RWE) is being used for HTAs of new lung and blood cancer therapies. We reviewed twenty HTA submissions for new therapies. All twenty were submitted to these agencies: National Institute for HealthCare and Excellence (NICE; UK), Scottish Medicines Consortium (SMC; Scotland), Canadian Agency for Drugs and Technologies in Health (CADTH; Canada), National Institute of Excellence in Health and Social Services (INESSS; Quebec), French National Authority for Health (HAS; France) and Institute for Quality and Efficiency in HealthCare (IQWiG; Germany). RWE was often used to describe the type of patient that needs the new therapy. RWE was also used to show the cost of the treatment and how well the treatment worked in relation to its cost. It was also used to show how well the new therapy works compared with other treatments. Most of the RWE was accepted by the agencies. High-quality RWE in relevant patients helped support access to new treatments.

Patient-reported health-related quality of life from the phase III TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone versus placebo-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma.

TOURMALINE-MM1 is a phase III, randomized, double-blind, placebo-controlled study of ixazomib plus lenalidomide and dexamethasone (IRd) versus placebo-Rd in patients with relapsed/refractory multiple myeloma following 1-3 prior lines of therapy. The study met its primary endpoint, demonstrating significantly longer progression-free survival (PFS) in the IRd arm versus placebo-Rd arm (median 20.6 vs 14.7 months, hazard ratio 0.74, P = .01), with limited additional toxicity. Patient-reported health-related quality of life (HRQoL) was a secondary endpoint of TOURMALINE-MM1. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQ-C30) and Multiple Myeloma Module 20 (QLQ-MY20) were completed at screening, the start of cycles 1 and 2, every other cycle, the end of treatment, and every 4 weeks until progression. Over median follow-up of 23.3 and 22.9 months in the IRd and placebo-Rd arms, mean QLQ-C30 global health status (GHS)/QoL scores were maintained from baseline over the course of treatment in both groups, with no statistically significant differences between groups. EORTC QLQ-C30 function domain scores were also generally maintained from baseline; similarly, physical, emotional, and social function domains were maintained with IRd versus placebo-Rd, with slightly higher mean change from baseline scores at earlier time points with IRd. Findings from this double-blind study demonstrate that addition of ixazomib to Rd significantly improved efficacy while HRQoL was maintained, reflecting the limited additional toxicity seen with IRd versus placebo-Rd, and support the feasibility of long-term IRd administration.

Real-World Treatment Patterns, Outcomes, and Healthcare Resource Utilization in Relapsed or Refractory Multiple Myeloma: Evidence from a Medical Record Review in France.

BACKGROUND: Limited data are available from real-world practices in Europe describing prevailing treatment patterns and outcomes in relapsed/refractory multiple myeloma (RRMM), particularly by cytogenetic risk. METHODS: A retrospective medical record review was conducted in 200 RRMM patients in France. From first relapse, patients were assessed on second-/third-line treatments, progression-free survival (PFS), overall survival (OS), and healthcare utilization. RESULTS: Fifty-five high risk and 113 standard risk patients were identified. Overall, 192 patients (96%) received second-line therapy after relapse. Lenalidomide-based regimens were most common (>50%) in second line. Hospitalization incidence in high risk patients was approximately twice that of standard risk patients. From Kaplan-Meier estimation, median (95% CI) second-line PFS was 21.4 (17.5, 25.0) months (by high versus standard risk: 10.6 [6.4, 17.0] versus 28.7 [22.1, 37.3] months). Among second-line recipients, 47.4% were deceased at data collection. Median second-line OS was 59.4 (38.8, NE) months (by high versus standard risk: 36.5 [17.4, 50.6] versus 73.6 [66.5, NE] months). CONCLUSIONS: The prognostic importance of cytogenetic risk in RRMM was apparent, whereby high (versus standard) risk patients had decidedly shorter PFS and OS. Frequent hospitalizations indicated potentially high costs associated with RRMM, particularly for high risk patients. These findings may inform economic evaluations of RRMM therapies.

Alisertib in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer or Recurrent Ovarian Cancer: A Randomized Clinical Trial.

Importance: There is an unmet medical need for the treatment of recurrent ovarian cancer, and new approaches are needed to improve progression-free survival (PFS) and overall survival. Objective: This phase 1/2 study evaluated the activity of alisertib in combination with weekly paclitaxel in patients with breast (phase 1) and ovarian cancer (phase 1 and phase 2). Design, Setting, and Participants: An open-label phase 1 and randomized phase 2 clinical trial conducted from April 16, 2010, for phase 1 and March 28, 2012, to August 12, 2013, for phase 2 was conducted at 33 sites (United States, France, and Poland). Data are reported from a cutoff date of August 12, 2014, with a median duration of follow-up of 7.2 months in the alisertib plus paclitaxel arm and 4.6 months in the paclitaxel arm. A total of 191 women with advanced breast (phase 1 only) or recurrent ovarian cancer were enrolled, including 142 patients randomized to alisertib plus paclitaxel (n = 73) or paclitaxel alone (n = 69) in the phase 2 study. Interventions: Patients were randomized 1:1 stratified by platinum-free interval (refractory, 0-6 months, 6-12 months) and prior weekly taxane treatment (yes, no) to receive alisertib 40 mg twice per day orally and 3 days on and 4 days off for 3 weeks, plus paclitaxel (60 mg/m2 intravenously, days 1, 8, and 15), or weekly paclitaxel 80 mg/m2 intravenously in 28-day cycles. Main Outcomes and Measures: Primary endpoint was PFS; primary efficacy analysis and safety analysis used modified intention to treat (mITT) population (all randomized patients who received ≥1 dose of study drug). Results: The median age for the 191 patients enrolled in phase 1 was 59 (range, 29-75) years. The median age for the 142 patients enrolled in phase 2 was 63 (range, 30-81) years for patients receiving alisertib plus paclitaxel and 61 (range, 41-81) years for patients receiving paclitaxel. At data cutoff, 107 (75%) patients had a documented PFS event; 52 (71%) in the alisertib plus paclitaxel arm, and 55 (80%) in the paclitaxel arm. Median PFS was 6.7 months with alisertib plus paclitaxel vs 4.7 months with paclitaxel (HR, 0.75; 80% CI, 0.58-0.96; P = .14; 2-sided P value cutoff = .20 to be considered worthy of further investigation). Drug-related grade 3 or higher adverse events were reported in 63 (86%) vs 14 (20%) patients in the alisertib plus paclitaxel and paclitaxel arms, including 56 (77%) vs 7 (10%) neutropenia, 18 (25%) vs 0 stomatitis, and 10 (14%) vs 2 (3%) anemia; 54 (74%) vs 17 (25%) had adverse events leading to dose reductions. Two patients died during the study (1 in each arm); neither death was considered related to study drug. Conclusions and Relevance: The primary endpoint, PFS, significantly favored alisertib plus paclitaxel over paclitaxel alone. Further investigation is warranted. Trial Registration: ClinicalTrials.gov identifier: NCT01091428.

Treatment patterns and health care resource utilization among patients with relapsed/refractory systemic light chain amyloidosis.

BACKGROUND: Treatment for patients with systemic light chain (AL) amyloidosis remains challenging. Our study aims to describe treatment patterns for both newly diagnosed and relapsed/refractory AL (RRAL) amyloidosis, and to assess clinical outcomes, healthcare costs, and resource utilization during the first year following a diagnosis of RRAL amyloidsis. METHODS: This was a retrospective observational study of adult patients with AL amyloidosis using the US Optum administrative claims data during 1/1/2008 to 6/30/2015. Diagnosis was based on both ICD-9 codes and treatments with a claim for AL-amyloidosis-specific anticancer systemic agents. RESULTS: Of 334 patients with AL amyloidosis, 43.1% were considered as RRAL amyloidosis. The majority (75%) of RRAL amyloidosis patients had organ involvement prior to the second line treatment. Proteasome-inhibitor-based regimens were most frequently used (41.0% for first-line AL, 30.6% for RRAL amyloidosis). Organ deterioration and mortality rates were 49.3% and 10.4%, respectively, during the two years following relapse. The average monthly cost was $14,369 per patient for RRAL amyloidosis including medical costs ($9441) and drug costs ($4928). CONCLUSIONS: RRAL amyloidosis is associated with high morbidity from target organ failure and mortality, which emphasizes the need for novel medications to improve care for patients with RRAL amyloidosis.

Healthcare resource utilization with ixazomib or placebo plus lenalidomide-dexamethasone in the randomized, double-blind, phase 3 TOURMALINE-MM1 study in relapsed/refractory multiple myeloma.

AIMS: The aim of this analysis was to assess healthcare resource utilization in the pivotal phase 3 TOURMALINE-MM1 study of the oral proteasome inhibitor ixazomib or placebo plus lenalidomide and dexamethasone (Rd) in relapsed and/or refractory multiple myeloma (RRMM). METHODS: In this double-blind, placebo-controlled, randomized study (NCT01564537), 722 patients with RRMM following 1-3 prior lines of therapy received Rd plus ixazomib (ixazomib-Rd; n = 360) or matching placebo (placebo-Rd; n = 362) until disease progression or unacceptable toxicity. Healthcare resource utilization data were captured on Day 1 of each 28-day cycle, every 4 weeks during follow-up for progression-free survival, and every 12 weeks during subsequent follow-up, and included medical encounters (length of stay, inpatient, outpatient, and reason) and number of missing days from work or other activities for patients and caregivers. RESULTS: Exposure-adjusted rates of hospitalization were similar between the ixazomib-Rd and placebo-Rd arms, at 0.530 and 0.564 per patient year (ppy), respectively, as were outpatient visit rates (3.305 and 3.355 ppy). Mean length of hospitalization per patient was 10.0 and 10.8 days, respectively. In both arms, hospitalization and outpatient visit rates were higher in patients with two or three prior lines of treatment (ixazomib-Rd: 0.632 and 3.909 ppy; placebo-Rd: 0.774 and 3.539 ppy) compared with patients with one prior line (ixazomib-Rd: 0.460 and 2.888 ppy; placebo-Rd: 0.436 and 3.243 ppy). Patients and their caregivers who missed any work or other activity missed a median of 7 and 5 days in the ixazomib-Rd arm, respectively, vs 8 and 4 days with placebo-Rd. LIMITATIONS: The study was not powered for a statistical comparison of healthcare resource utilization between treatment arms, nor did it capture costs associated with utilization of the identified healthcare resources. CONCLUSIONS: This pre-specified analysis demonstrated that the all-oral triplet regimen of ixazomib added to Rd did not increase healthcare resource utilization compared with placebo-Rd.

Disease burden of systemic light-chain amyloidosis: a systematic literature review.

INTRODUCTION: A systematic literature review on systemic light chain (AL) amyloidosis was conducted in order to understand the disease burden, and identify unmet medical needs and knowledge gaps. METHODS: MEDLINE, Embase and Cochrane databases were searched for English language studies published in the last 10 years using search terms that focused on the clinical, economic, and patient-reported outcome (PRO) aspects of AL amyloidosis. There was a low yield of articles in the economic and PRO categories and additional searches were conducted in clinical conference proceedings, and using Google and Google Scholar. After review, there were 65 articles included for data extraction. RESULTS: AL amyloidosis is a rare disorder without any FDA or EMA approved indications for drug therapy. Using off-label therapies, there is a high rate, 42-64%, of non-response or progression, and an associated high mortality. Toxicities during therapy are common with estimates of up to 30-40% of patients experiencing severity of grade 3 or higher. Patients with AL amyloidosis report severe psychological distress, anxiety and clinical depression. CONCLUSIONS: There is a deficiency in the literature on the economic costs associated with AL amyloidosis, and information on costs has been derived from studies that examined multiple myeloma or other disease or treatment components common to AL amyloidosis.

Clinical and economic burden of peripheral T-cell lymphoma in commercially insured patients in the United States: findings using real-world claims data.

OBJECTIVE: This retrospective cohort study utilized real-world claims data to assess the clinical and economic burden of peripheral T-cell lymphoma (PTCL) over the continuum of care in the US. METHODS: Data were extracted from US administrative claims databases to identify adult patients with PTCL (ICD-9-CM code 202.7X) diagnosed between October 2007 and June 2011. Patients had to have ≥6 months of continuous enrollment before and ≥12 months of continuous enrollment after their index date (date of first PTCL diagnosis). PTCL patients were matched (1:5) by age, sex, region, plan type, payer type, and length of continuous enrollment, to a control group of randomly selected patients without PTCL. Patient-level healthcare resource utilization data and associated costs (in US dollars) were measured. Mean costs per patient per month were determined. RESULTS: Of 2820 patients with PTCL, 1000 met all inclusion criteria (median age = 57 years; 57.5% male) and were matched to the control group (n = 5000). On an average monthly basis, PTCL patients were hospitalized more frequently (0.07 vs 0.01 admissions; p < 0.0001) and had a longer length of hospital stay (6.4 vs 4.0 days; p < 0.0001) compared with controls. PTCL patients also had higher monthly utilization of pharmacy services (2.85 vs 0.97 prescriptions; p < 0.0001), office visits (1.35 vs 0.34 visits; p < 0.0001), ER visits (0.07 vs 0.02 visits; p < 0.0001), hospice stays (0.05 vs 0.01 stays; p < 0.0001) and other patient services/procedures. Overall, PTCL patients incurred higher average monthly costs per patient compared with control patients ($6327.84 vs $388.39; p < 0.0001), driven mainly by hospitalizations (32.2% of overall costs) and pharmacy services (19.6%). CONCLUSIONS: This is the first real-world study to quantify healthcare resource utilization, costly treatment, and overall medical expenditure in commercially insured PTCL patients. Better tolerated and more effective treatments may improve disease management and reduce the clinical and economic burden of PTCL.

The patient's perspective on the symptom and everyday life impact of AL amyloidosis.

INTRODUCTION: This study aimed to understand the symptomatic impact of amyloid light-chain (AL) amyloidosis from the patient's perspective. METHODS: Four data sources were included: a literature review, review of online patient blogs, expert clinician interviews and patient interviews. Patients were recruited through the Amyloidosis Foundation and physician referral. Phone interviews were conducted and included open-ended concept elicitation questions. Thematic analysis was performed to identify symptoms and impacts. Descriptive statistics were used to characterize the sample. A conceptual model was developed depicting the impact of disease and treatment. RESULTS: Two hundred seventy abstracts were identified; 10 articles were deemed relevant. No qualitative studies were identified, and only three studies included patient-reported measures. Ten patients completed interviews (mean age 61 [±8]; 7 male). Over 25 signs/symptoms were identified, including fatigue, weakness, dyspnea, neuropathy, edema, dizziness/lightheadedness, anorexia, diarrhea and constipation. Impacts included reduced physical and social functioning, and emotional impacts, including frustration, anxiety and depression. Findings from the blogs and expert interviews were consistent with patient reports. CONCLUSION: Symptoms can vary widely, but a core set of symptoms were common across patients. The conceptual model derived from this study can be used to ensure a patient-centered approach to drug development.