Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable Driver Oncogenes.

BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.

Improving biomarker testing in advanced non-small-cell lung cancer and metastatic colorectal cancer: experience from a large community oncology network in the USA.

Aim: Biomarker testing detects actionable driver mutations to inform first-line treatment in advanced non-small-cell lung cancer (aNSCLC) and metastatic colorectal cancer (mCRC). This study evaluated biomarker testing in a nationwide database (NAT) versus the OneOncology (OneOnc) community network. Patients & methods: Patients with aNSCLC or mCRC with ≥1 biomarker test in a de-identified electronic health record-derived database were evaluated. OneOnc oncologists were surveyed. Results: Biomarker testing rates were high and comparable between OneOnc and NAT; next-generation sequencing (NGS) rates were higher at OneOnc. Patients with NGS versus other biomarker testing were more likely to receive targeted treatment. Operational challenges and insufficient tissue were barriers to NGS testing. Conclusion: Community cancer centers delivered personalized healthcare through biomarker testing.

What is this article about? Cancer therapies often work better in certain subgroups of patients. Tumors may have characteristics that can predict which therapies may be more likely to work. These cancer biomarkers may be identified by special testing, such as next-generation sequencing (NGS). If a biomarker is detected, the patient can potentially be treated with medicine that targets that biomarker. This study looked at biomarker testing of lung and colon cancers in two community cancer practices (OneOncology [OneOnc] and nationwide database [NAT]). What were the results? The biomarker testing rates were high (≥81%) and similar between OneOnc and NAT. NGS testing rates were higher at OneOnc than at NAT (58 vs 49% for non-small-cell lung cancer, 55 vs 42% for metastatic colorectal cancer [mCRC]), suggesting the success of OneOnc's networkwide educational, pathway and operational programs. NGS testing was lower in community practices due to operational challenges and insufficient tissue collection. Patients who had NGS versus other biomarker testing were more likely to receive treatment specifically for that biomarker. However, some patients started treatment before their biomarker results were reported, usually because of their disease and a long wait time for biomarker test results. What do the results of the study mean? Community cancer centers can treat patients with targeted medicine based on biomarker testing results. There are opportunities to increase the number of patients getting NGS testing, shorten turnaround times and reduce the number of patients who start treatment before getting their biomarker test results.

Venetoclax and Hypomethylating Agents as First-line Treatment in Newly Diagnosed Patients with AML in a Predominately Community Setting in the US.

BACKGROUND: Treatment with venetoclax + hypomethylating agents (HMAs) is standard-of-care for newly diagnosed (ND) patients with acute myeloid leukemia (AML) aged ≥75 years, or with comorbidities precluding intensive chemotherapy. We describe real-world venetoclax + HMA treatment practices and outcomes in patients with ND AML in the US. PATIENTS AND METHODS: This retrospective cohort study used an electronic health record-derived, US nationwide, de-identified database, and included adults with ND AML, initiating venetoclax + HMA treatment ≤30 days from diagnosis (June 1, 2018-January 31, 2020). Venetoclax treatment variables included dosing information, schedule modifications, and drug-drug interactions. The median venetoclax + HMA treatment duration and overall survival (OS) from venetoclax initiation to discontinuation, death, or end of follow-up (August 31, 2020) were examined by Kaplan-Meier analyses. RESULTS: Overall, 169 patients were included. The median age at diagnosis was 77 years; 85.2% of patients were treated in community practice. Ninety-five of 169 patients (56.2%) had evaluable bone marrow response data following the start of treatment; 53.7% were assessed approximately at the end of cycle 1. Following the first treatment cycle, treatment schedule modifications were recorded in 101 patients and dose changes in 56, primarily due to toxicity. The median treatment duration was 5.2 months; the median OS was 8.6 months (median follow-up was 7.2 months). Venetoclax dose changes did not modify efficacy outcomes, but longer median OS was associated with venetoclax treatment schedule modifications (P = .02). CONCLUSIONS: This study reflects early real-world experience with venetoclax + HMAs in a predominantly community setting and emphasizes the importance of appropriate venetoclax management in optimizing patient outcomes.

Racial and Ethnic Inequities at the Practice and Physician Levels in Timely Next-Generation Sequencing for Patients With Advanced Non-Small-Cell Lung Cancer Treated in the US Community Setting.

PURPOSE: Racial/ethnic inequities in next-generation sequencing (NGS) were examined for patients with advanced non-small-cell lung cancer (aNSCLC) at the practice and physician levels to inform policies to improve equitable quality of care. METHODS: This retrospective study used a nationwide electronic health record-derived deidentified database for patients with aNSCLC diagnosed between April 2018 and March 2022 in the community setting. Timely NGS was an NGS result between initial diagnosis and ≤60 days after advanced diagnosis. We studied how inequities were driven by (1) non-Latinx Black (Black) and Latinx patient under-representation at high testing practices versus (2) Black and Latinx patients being tested at lower rates than non-Latinx White (White) patients, even at the same practice. We defined these two concepts as across inequity and within inequity, respectively, with total inequity as their summation. Mean percentage point inequities were estimated using a Bayesian approach. RESULTS: A total of 12,045 patients (9,981 White; 1,528 Black; 536 Latinx) met study criteria. At the practice level, versus White patients, the mean percentage point difference in NGS testing total inequity was 7.49 for Black and 8.26 for Latinx. Within- and across-practice inequities contributed to total inequity in NGS testing for Black (48% v 52%) and Latinx patients (60% v 40%). At the physician level, versus White patients, the mean percentage point difference in total inequity was 7.73 for Black and 8.81 for Latinx patients. Within- versus across-physician inequities contributed to total inequity for Black and Latinx patients (77% v 23% and 67% v 33%). CONCLUSION: Within-practice, across-practice, and across-physician inequities were main contributors to total inequity in NGS testing, requiring a suite of interventions to effectively address inequities.

Post-remission cytopenia management in patients with AML treated with venetoclax in combination with hypomethylating agents: Pre- versus post-VIALE-A real-world experience from a predominantly US community setting.

BACKGROUND: This retrospective cohort study used an electronic health record-derived, de-identified, US patient-level database to better understand the real-world treatment experience, in a predominantly community setting (80.3% of patients), of venetoclax+hypomethylating agents (HMAs) in routine clinical care, pre- and post-VIALE-A, to determine whether the post-remission cytopenia management insight from VIALE-A was reflected in real-world clinical practice. METHODS: Patients with newly diagnosed acute myeloid leukemia (AML; N = 498), who initiated venetoclax+HMA ≤30 days from AML diagnosis from June 1, 2018, to March 31, 2021, were stratified into pre-(n = 330) and post-(n = 168) VIALE-A cohorts. RESULTS: More patients in the post-(61%) versus pre-(45%) VIALE-A cohort had their first biopsy by 28 ± 14 days post-treatment initiation. Patients underwent bone marrow (BM) assessment earlier in the post- versus pre-VIALE-A cohort, and first identification of response was also earlier (2.5 vs 5.1 months, respectively). More venetoclax schedule modifications post-remission occurred among post-(82.1%) versus pre-(73.8%) VIALE-A responders; the most common reason for modification was treatment toxicities, specifically cytopenia. Treatment survival outcomes were comparable with or without venetoclax schedule modifications. CONCLUSIONS: Findings suggest that venetoclax schedule modifications can be used to manage cytopenia events without adversely affecting outcomes. Opportunities remain to improve earlier BM assessment to determine venetoclax schedule modifications, providing the best chance for optimal treatment outcomes.

Early Real-World First-Line Treatment With Venetoclax Plus HMAs Versus HMA Monotherapy Among Patients With AML in a Predominately US Community Setting.

BACKGROUND: Venetoclax in combination with hypomethylating agents (HMAs) is standard-of-care in patients with newly diagnosed acute myeloid leukemia (AML) who are ≥ 75 years old or unfit for intensive chemotherapy. We examined early real-world treatment experience among patients with AML receiving venetoclax+HMAs or HMA monotherapy. PATIENTS AND METHODS: This retrospective cohort study used an electronic health record-derived, deidentified, United States nationwide database comprised of patient-level structured and unstructured data, curated via technology-enabled abstraction. Patients with an AML diagnosis on or after January 1, 2014, who had ≥ 2 clinic visits, and initiated treatment with venetoclax+HMAs from June 1, 2018 to March 31, 2021, or HMA monotherapy from January 1, 2016 to May 31, 2018, were included. Kaplan-Meier analysis was used to estimate time to last administration (TTLA) and overall survival (OS). RESULTS: Overall, 619 patients treated with venetoclax+HMAs and 480 treated with HMA monotherapy were selected from the database. Median age at diagnosis was 76 and 78 years, respectively, most patients were treated in community practice (83.4% and 89.4%, respectively), and almost half had secondary AML (47.2% and 47.3%, respectively). Adjusted analyses showed both significantly longer TTLA (3.6 months vs. 2.3 months; hazard ratio [HR] = 0.69 [95% confidence interval (CI), 0.60-0.80], P< .0001) and OS (9.3 months vs. 5.9 months; HR = 0.71 [95% CI, 0.61-0.82], P < .0001) in patients treated with venetoclax+HMAs versus HMA monotherapy, respectively. CONCLUSION: This study shows benefit in real-world outcomes of venetoclax+HMAs relative to HMA monotherapy in patients with newly diagnosed AML, using a predominantly community-based database.

Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective.

OBJECTIVES: Using individual patient-level data from the phase 3 VIALE-A trial, this study assessed the cost-effectiveness of venetoclax in combination with azacitidine compared with azacitidine monotherapy for patients newly diagnosed with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy, from a United States (US) third-party payer perspective. METHODS: A partitioned survival model with a 28-day cycle and three health states (event-free survival (EFS), progressive/relapsed disease, and death) was developed to estimate costs and effectiveness of venetoclax + azacitidine versus azacitidine over a lifetime (25-year) horizon. Efficacy inputs (overall survival (OS), EFS, and complete remission (CR)/CR with incomplete marrow recovery (CRi) rate) were estimated using VIALE-A data. Best-fit parametric models per Akaike Information Criterion were used to extrapolate OS until reaching EFS and extrapolate EFS until Year 5. Within EFS, the time spent in CR/CRi was estimated by applying the CR/CRi rate to the EFS curve. Past Year 5, patients still in EFS were considered cured and to have the same mortality as the US general population. Mean time on treatment (ToT) for both regimens was based on the time observed in VIALE-A. Costs of drug acquisition, drug administration (initial and subsequent treatments), subsequent stem cell transplant procedures, adverse events (AEs), and healthcare resource utilization (HRU) associated with health states were obtained from the literature/public data and inflated to 2021 US dollars. Health state utilities were estimated using EuroQol-5 dimension-5 level data from VIALE-A; AE disutilities were obtained from the literature. Incremental cost-effectiveness ratios (ICERs) per life-year (LY) and quality-adjusted life-year (QALY) gained were estimated. Deterministic sensitivity analyses (DSA), scenario analyses, and probabilistic sensitivity analyses (PSA) were also performed. RESULTS: Over a lifetime horizon, venetoclax + azacitidine versus azacitidine led to gains of 1.89 LYs (2.99 vs. 1.10, respectively) and 1.45 QALYs (2.30 vs. 0.84, respectively). Patients receiving venetoclax + azacitidine incurred higher total lifetime costs ($250,486 vs. $110,034 (azacitidine)). The ICERs for venetoclax + azacitidine versus azacitidine were estimated at $74,141 per LY and $96,579 per QALY gained. Results from the DSA and scenario analyses supported the base-case findings, with ICERs ranging from $60,718 to $138,554 per QALY gained. The results were most sensitive to varying the parameters for the venetoclax + azacitidine base-case EFS parametric function (Gompertz), followed by alternative approaches for ToT estimation, treatment costs of venetoclax + azacitidine, standard mortality rate value and ToT estimation, alternative sources to inform HRU, different cure modeling assumptions, and the parameters for the venetoclax + azacitidine base-case OS parametric function (log-normal). Results from the PSA showed that, compared with azacitidine, venetoclax + azacitidine was cost-effective in 99.9% of cases at a willingness-to-pay threshold of $150,000 per QALY. CONCLUSIONS: This analysis suggests that venetoclax + azacitidine offers a cost-effective strategy in the treatment of patients with newly diagnosed AML who are ineligible for intensive chemotherapy from a US third-party payer perspective. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02993523. Date of registration: 15 December 2016.

Costs per patient achieving remission with venetoclax-based combinations in newly diagnosed patients with acute myeloid leukemia ineligible for intensive induction chemotherapy.

BACKGROUND: Venetoclax, in combination with azacitidine, decitabine, or low-dose cytarabine (LDAC), received confirmatory approval in 2020 by the US Food and Drug Administration for the treatment of newly diagnosed acute myeloid leukemia (AML) in patients aged 75 years or older or who are ineligible for intensive induction chemotherapy. The economic value associated with response to venetoclax combinations compared with other treatments for this patient population has not been comprehensively evaluated. OBJECTIVE: To assess the cost per patient achieving remission with venetoclax combination therapies, compared with other therapies for newly diagnosed patients with AML who are ineligible for intensive induction chemotherapy, from a US third-party payer perspective. METHODS: The analysis used treatment effect estimates (ie, complete remission [CR] + CR with incomplete blood count recovery [CRi]) from a network meta-analysis and annual cost estimates from a prior budget impact model. The model considered the total cost of care including the costs of drug and administration, adverse events, hospitalization, disease monitoring, blood transfusions, and subsequent AML management when patients discontinued active treatment. Costs per patient achieving CR + CRi associated with venetoclax + azacitidine, venetoclax + LDAC, azacitidine, decitabine, LDAC, and best supportive care (ie, treatment given with the intent to maximize quality of life without specific antileukemic intent, such as blood transfusion products and antibiotics) were calculated as the annual total cost of care per patient divided by the CR + CRi rate. All costs were adjusted to 2020 US dollars. RESULTS: Venetoclax combination therapies were estimated to have substantially lower costs per patient achieving CR + CRi (venetoclax + azacitidine: $473,960; venetoclax + LDAC: $428,071) than alternative treatments. Azacitidine was estimated to have the the highest cost per patient achieving CR + CRi ($1,197,438), followed by best supportive care ($869,849), LDAC ($689,101), and decitabine ($594,074). A pair-wise matrix of the difference between therapies estimated that both venetoclax + azacitidine and venetoclax + LDAC were associated with significantly lower costs per patient achieving CR + CRi than azacitidine (by $723,477 and $769,367, respectively) and LDAC (by $215,141 and $261,030; all P < 0.05). CONCLUSIONS: From a US third-party payer perspective, venetoclax in combination with azacitidine or LDAC was estimated to be associated with a significantly lower cost per patient achieving CR + CRi than azacitidine or LDAC among newly diagnosed patients with AML ineligible for intensive chemotherapy. DISCLOSURES: This research was supported by AbbVie Inc. and Genentech. The sponsors helped design the study, interpret the data, and draft the manuscript. Drs Bui and Kapustyan are employees of and have equity ownership in AbbVie; Dr Choi was an employee of AbbVie during the study's conduct and has equity ownership. Ms Ma and Dr Montez are employees of and have equity ownership in Genentech. Drs Song and Chai, Ms Yin, and Dr Betts are employees of Analysis Group, Inc., which has received funding from AbbVie and Genentech for the conduct of this research. Dr LeBlanc reports personal fees for consulting or advisory boards from AbbVie, Agios/Servier, AstraZeneca, Amgen, Astellas, BlueNote, CareVive, BMS/Celgene, Daiichi-Sankyo, Flatiron, Genentech, GSK, Pfizer, and Seattle Genetics; royalties from UpToDate; speakers bureau fees from Agios/Servier, AbbVie, and BMS/Celgene; and grants and/or research contracts from the American Cancer Society, AstraZeneca, BMS, Jazz Pharmaceuticals, and Seattle Genetics.

Treatment patterns and outcomes according to cytogenetic risk stratification in patients with multiple myeloma: a real-world analysis.

A clearer understanding of the prognostic implications of t(11;14) in multiple myeloma (MM) is needed to inform current and future therapeutic options. We utilized real-world data from a US database to examine treatment patterns and outcomes in patients by t(11;14) status compared with high- and standard-risk subgroups across different lines of therapy (LoT). This retrospective, observational cohort study used de-identified patient-level information from adults with MM and first-line treatment initiation between January 2011 and January 2020, followed until February 2020. The high-risk cohort comprised patients with high-risk genetic abnormalities per mSMART criteria (including those with co-occurring t(11;14)). Among 6138 eligible patients, 6137, 3160, and 1654 received first-, second-, and third-line treatments, respectively. Of 645 patients who had t(11;14), 69.1% had t(11;14) alone, while 30.9% had co-occurring high-risk abnormalities. Altogether, 1624 and 2544 patients were classified as high- and standard-risk, respectively. In the absence of biomarker-driven therapy, treatment patterns remain similar across LoT in high-risk, t(11;14)+, and standard-risk subgroups. Across all LoT, patient outcomes in the high-risk subgroup were less favorable than those in the t(11;14)+ and standard-risk subgroups. Thus, there is an opportunity for novel therapeutics targeted to t(11;14) and other defined subgroups to personalize MM therapy and optimize patient outcomes.

Brentuximab vedotin consolidation post-autologous stem cell transplant in Hodgkin lymphoma patients at risk of residual disease: number needed to treat.

The number needed to treat (NNT) with brentuximab vedotin consolidation therapy post-autologous stem cell transplant (ASCT) versus placebo in the phase 3 AETHERA trial to avoid one additional event of disease progression/death was evaluated. AETHERA included 329 Hodgkin lymphoma patients at increased risk of progression post-ASCT who received brentuximab vedotin 1.8 mg/kg (n = 165) or placebo (n = 164) on day 1 of each 21-d cycle (up to 16 cycles). Over 60 months, the NNT with brentuximab vedotin ranged from 4.08 to 7.79 for the intent-to-treat population, 3.18-6.07 for patients with ≥2 risk factors, and 2.98-5.65 for patients with ≥3 risk factors. At various time points, and dependent on the risk group, 3-8 patients would need to be treated with brentuximab vedotin consolidation therapy to prevent a disease progression/death, compared with placebo. Patients with increased risk of relapse may benefit most from brentuximab vedotin.

A Cost-effectiveness Analysis of Brentuximab Vedotin in Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma.

Objective: To evaluate the cost-effectiveness of brentuximab vedotin in patients with R/R sALCL from a UK NHS perspective. Methods: A partitioned survival model used clinical outcomes for brentuximab vedotin from the pivotal phase-2 single-arm trial of brentuximab vedotin in 58 patients with R/R sALCL (SG035-0004; NCT00866047), over a lifetime (30-year) time horizon. Comparison with conventional chemotherapy was based on data from the Canadian British Columbia Cancer Agency registry from 40 patients starting salvage chemotherapy after front-line treatment between 1980 and 2012. Survival was extrapolated using parametric distributions, with brentuximab vedotin risk after the trial period assumed equal to conventional chemotherapy. Other modelling assumptions were based on a systematic literature review and clinical expert opinion. Results: Based on statistical extrapolation, brentuximab vedotin was associated with 3.1 years longer duration in the progression-free survival health state and an overall survival improvement of 5.4 years, prior to discounting. In addition, brentuximab vedotin was associated with 2.5 quality-adjusted life years (QALYs) gained at a total incremental cost of £88 556, resulting in an incremental cost-effectiveness ratio (ICER) of approximately £35 400. Sensitivity analyses of alternative model assumptions provided ICERs ranging from approximately £28 100 to £61 900. Comparing only first-line salvage patients reduced the ICER to £26 800 per QALY gained. Conversely, considering only patients with Eastern Corporative Oncology Group performance status of 0 or 1 increased the ICER to approximately £38 200. At a willingness-to-pay threshold of £50 000, the estimated probability that brentuximab vedotin is cost-effective compared with conventional chemotherapy was 86.5%. Conclusion: Compared to conventional chemotherapy, and considering the full survival period, brentuximab vedotin may provide a valuable treatment choice for patients with R/R sALCL, a population with limited therapeutic options.

Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis.

AIM: To conduct a cost-effectiveness analysis to compare ocrelizumab vs subcutaneous (SC) interferon beta-1a for the treatment of relapsing multiple sclerosis (RMS). METHODS: A Markov cohort model with a 20-year horizon was developed to compare ocrelizumab with SC interferon beta-1a from a US payer perspective. A cohort of patients with relapsing-remitting MS (RRMS) and Expanded Disability Status Scale (EDSS) scores of 0-6, who initiated treatment with ocrelizumab or SC interferon beta-1a, were entered into the model. The model considered 21 health states: EDSS 0-9 in RRMS, EDSS 0-9 in secondary-progressive multiple sclerosis (SPMS), and death. Patients with RRMS could transition across EDSS scores, progress to SPMS, experience relapses, or die. Transition probabilities within RRMS while patients received ocrelizumab or SC interferon beta-1a were based on data from the two SC interferon beta-1a-controlled Phase III OPERA I and OPERA II trials of ocrelizumab in RMS. Transitions within RRMS when off-treatment, RRMS-to-SPMS transitions, transitions within SPMS, and transitions to death were based on the literature. Utilities of health states, disutilities of relapses, costs of therapies, and medical costs associated with health states, relapse, and adverse events were from the literature and publicly available data sources. The model estimated per-patient total costs, incremental cost per life year (LY) gained, and incremental cost per quality-adjusted LY (QALY) gained. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were conducted to evaluate the robustness of the model results. RESULTS: Ocrelizumab was associated with a cost savings of $63,822 and longer LYs (Δ = 0.046) and QALYs (Δ = 0.556) over a 20-year time horizon. The results of the model were robust in the DSA and PSA. LIMITATIONS: The model did not consider subsequent treatments and their impact on disease progression. CONCLUSIONS: The results suggest that ocrelizumab is more cost-effective than SC interferon beta-1a for the treatment of RMS.

Brentuximab vedotin in relapsed/refractory Hodgkin lymphoma post-autologous stem cell transplant: a cost-effectiveness analysis in Scotland.

OBJECTIVE: To evaluate cost-effectiveness of brentuximab vedotin in patients with relapsed/refractory Hodgkin lymphoma who have received autologous stem cell transplantation, from a Scottish healthcare payer perspective. METHODS: A Microsoft Excel-based partitioned survival model comprising three health states (progression-free survival [PFS], post-progression survival, and death) was developed. Relevant comparators were chemotherapy with or without radiotherapy (C/R) and C/R with intent to allogeneic hematopoietic stem cell transplantation (alloSCT). Data were obtained from the pivotal phase II single-arm trial in 102 patients (SG035-0003; NCT00848926), a systematic literature review and clinical expert opinions (where empirical evidence was unavailable). PFS and overall survival for brentuximab vedotin were estimated using 5-year follow-up data from SG035-0003, and extrapolated using event rates observed for comparator treatments from published survival data. Resource use included drug acquisition and administration; alloSCT; treatment of adverse events; and long-term follow-up. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the impact of uncertainty. RESULTS: In the base case, the incremental cost-effectiveness ratio (ICER) for brentuximab vedotin was £38,769 per quality-adjusted life year (QALY) vs C/R, whereas C/R with intent to alloSCT was dominated by brentuximab vedotin. ICERs for brentuximab vedotin generated by the deterministic sensitivity analysis ranged between £32,000-£54,000 per QALY. Including productivity benefits reduced the ICER to £28,881 per QALY. LIMITATIONS: Limitations include lack of comparative data from this single arm study and the heterogeneous population. Inconsistent baseline characteristic reporting across studies prevented complete assessment of heterogeneity and the extent of potential bias in clinical and cost-effectiveness estimates. CONCLUSIONS: Although the base case ICER is above the threshold usually applied in Scotland, it is relatively low compared with other orphan drugs, and lower than the ICER generated using a previous data cut of SG035-0003 that informed a positive recommendation from the Scottish Medicines Consortium, under its decision-making framework for assessment of ultra-orphan medicines.

Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014).

PURPOSE: To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. METHODS: FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. RESULTS: Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. CONCLUSION: Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.

An Evaluation of Treatment Patterns and Outcomes in Elderly Patients Newly Diagnosed With Acute Myeloid Leukemia: A Retrospective Analysis of Electronic Medical Records From US Community Oncology Practices.

BACKGROUND: Many elderly patients with acute myeloid leukemia (AML) are considered ineligible for standard intensive induction therapy due to performance status and comorbidities. We analyzed treatment patterns and outcomes among elderly patients newly diagnosed with AML in the US community oncology setting. METHODS: A retrospective observational study was conducted using patient-level data from a network of US community oncology practices provided by Altos Solutions. Patients aged ≥ 60 years, diagnosed with AML between November 2005 and February 2014, with ≥ 1 recorded visit and ≥ 6 months between diagnosis and data cutoff, were included. Only patients who received active treatment or best supportive care (BSC) per National Comprehensive Cancer Network (NCCN) AML Guidelines were analyzed. RESULTS: Of 1139 patients meeting the inclusion criteria, 922 (median age 76 years) received NCCN-recommended treatments: standard induction (n = 5), low-intensity therapy (n = 425), BSC with hydroxyurea (HU) (n = 36), or BSC without HU (n = 455). For the low-intensity therapy cohort, median time from diagnosis to treatment initiation was 17 days; median duration of therapy was 5.1 months. Median overall survival (OS) from diagnosis in the low-intensity, BSC with HU, and BSC without HU groups was 12.3, 7.0, and 49.4 months, respectively. Median time to next therapy/death was 10.1 months in patients receiving low-intensity therapy. A higher proportion of patients receiving low-intensity therapy required transfusion or other supportive care versus those receiving BSC. CONCLUSIONS: As expected, OS in patients receiving low-intensity therapy or BSC with HU is poor for elderly patients with AML. Remarkably, intensive induction strategies are rarely used for older patients in community oncology practice.

Meta-analysis of the efficacy and safety of bortezomib re-treatment in patients with multiple myeloma.

INTRODUCTION: Bortezomib is administered for a finite course; thus, patients might remain sensitive to bortezomib-based therapy at relapse. We report a meta-analysis of bortezomib-based retreatment in relapsed/refractory myeloma. PATIENTS AND METHODS: A systematic literature review identified studies of bortezomib-based retreatment in relapsed/refractory myeloma. Proportions of bortezomib-refractory patients and additional prognostic factors were extracted and used in weighted stratified analyses of TTP and OS. Random-effect pooled estimates were calculated for overall response rate (ORR) and rates of common AEs. RESULTS: Twenty-three studies (n = 1051 patients) were identified. Bortezomib was administered intravenously in all studies. Across studies in which data were available, pooled, weighted average ORR was 39.1% (95% confidence interval, 30.8%-47.4%), and pooled, weighted average median TTP and OS were 7.5 and 16.6 months, respectively. Patients with fewer previous therapies (≤ 4) and relapsed (not refractory) patients achieved higher ORRs, of 43.4% and 57.2%, respectively. Random-effects meta-regression analysis confirmed that relapsed patients were associated with a higher ORR by 28 to 41 percentage points versus refractory patients. In relapsed patients, median TTP and OS were 8.5 and 19.7 months, respectively. Common Grade 3/4 AEs included thrombocytopenia (35%), neutropenia (15%), anemia (14%), pneumonia (10%), and peripheral neuropathy (3%). CONCLUSION: Based on these findings, bortezomib retreatment is well tolerated and appears efficacious in relapsed patients. In an era of new and emerging treatment options for relapsed and/or refractory myeloma, these data indicate that bortezomib retreatment might be a highly effective option in previously treated patients.