Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA.

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

Real-world adherence and discontinuation among Medicare beneficiaries initiating venetoclax vs. BTKis in relapsed/refractory chronic lymphocytic leukemia.

The treatment landscape for chronic lymphocytic leukemia (CLL) has been transformed by the availability of Bruton's tyrosine kinase inhibitors (BTKis) and the B-cell lymphoma 2 (BCL-2) inhibitor venetoclax. Despite clinical trial data supporting these novel oral agents, evidence evaluating real-world adherence is limited. This study used 2015-2019 Medicare claims data for elderly patients with relapsed/refractory CLL to assess differences in real-world adherence and discontinuation in the 12 months after treatment initiation. In the final sample of 711 venetoclax patients and 1,566 BTKi patients, we found that those initiating venetoclax tended to be younger (mean age 75.6 [SD 6.0] vs 77.6 [SD 6.9] years, p < .001) but had poorer clinical characteristics. After risk-adjustment, the venetoclax group had higher adherence (61.9% vs. 45.4%, p < .0001) and lower discontinuation when compared to the BTKi group (28.5% vs. 47.4%, p < .001). These favorable real-world findings underscore the importance of developing well-tolerated novel combinations for older adults.

Advance Directives for Patients With Breast Cancer: Applying the Right Info/Right Care/Right Patient/Right Time Oncology Model.

Background Advance directives (AD) are an important component of life care planning for patients undergoing treatment for cancer; however, there are few effective interventions to increase AD rates. In this quality improvement project, the authors integrated AD counseling into a novel right info/right care/right patient/right time (4R) sequence of care oncology delivery intervention for breast cancer patients in an integrated health care delivery system. Methods The authors studied two groups of patients with newly diagnosed breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at a single facility. The usual care (UC) cohort (N = 139) received care from October 1, 2019 to September 30, 2020. The 4R cohort (N = 141) received care from October 1, 2020 to September 30, 2121 that included discussing AD completion with a health educator prior to surgery. The authors used bivariate analyses to assess whether the AD intervention increased AD completion rates and to identify factors influencing AD completion. Results The UC and 4R cohorts were similar in age, gender, race/ethnicity, interpreter need, Elixhauser comorbidity index, National Comprehensive Cancer Network distress score ≥ 5, surgery type, stage, histology, grade, and Estrogen receptor/Progesterone receptor/ human epidermal growth factor receptor 2 (ER/PR/HER2) status. AD completion rates prior to surgery were significantly higher for the 4R vs UC cohort (73.8%, 95% confidence interval [CI] [66.5%-81.0%] vs 15.1%, 95% CI [9.2%-21.1%], p < .01) and did not significantly differ by age, race, need for interpreter, or distress scores. Conclusion Incorporation of a health educator discussion into a 4R care sequence plan significantly increased rates of time-sensitive AD completion.

Fostering a High-Functioning Team in Cancer Care Using the 4R Oncology Model: Assessment in a Large Health System and a Blueprint for Other Institutions.

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system. METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. RESULTS: We formed an internally and externally recognized team of 24 specialties committed to a shared goal of delivering multidisciplinary care at the optimal time and sequence from a patient-centric viewpoint. The team conducted 40 optimizations of interdependent care (22 for breast, seven for lung, and 11 for both cancers) at four points in the care continuum and established an ongoing teamwork adaptation process. Half of the optimizations entailed low effort, while 30% required high level of effort; 78% resulted in improved process efficiency. CONCLUSION: 4R facilitated development of a large high-functioning team and enabled 40 optimizations of interdependent care along the cancer care continuum in a feasible way. 4R may be an effective approach for fostering high-functioning teams, which could contribute to improving viability of the oncology workforce. Our intervention and taxonomy of results serve as a blueprint for other institutions motivated to strengthen teamwork to improve patient-centered care.

Cost-effectiveness of a 12-month fixed-duration venetoclax treatment in combination with obinutuzumab in first-line, unfit chronic lymphocytic leukemia in the United States.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a significant health and economic burden in the United States. Treatments include chemoimmunotherapy, such as obinutuzumab (G) plus chlorambucil (Clb) or bendamustine plus rituximab (BR), and chemotherapy-free regimens incorporating oral targeted therapies such as ibrutinib (Ibr), acalabrutinib (Acala), or venetoclax (Ven). Most chemotherapy-free regimens require continuous treatment to progression, while Ven plus G (VenG) is given for a fixed duration of 12 months, based on the CLL14 trial that led to its approval. Fixed-duration VenG has the potential for cost savings compared with treat-to-progression chemotherapy-free regimens. OBJECTIVE: To evaluate the cost-effectiveness of 12 months fixed-duration VenG in first-line treatment of unfit patients with CLL from a US health care payer perspective compared with GClb, BR, Ibr, Ibr + G, Ibr + R, Acala, and Acala + G. METHODS: A partitioned survival model was developed with 3 health states: progression-free survival (PFS), postprogression survival, and dead. The patient population, as based on the CLL14 trial, comprised previously untreated unfit patients with CLL (mean age 71.1 years, 33.1% female). The distribution of patients in each health state over time was estimated using extrapolated PFS and overall survival (OS) curves for VenG and GClb, based on CLL14 data 2 or more years after treatment cessation. PFS and OS for the other comparators were estimated using hazard ratios vs VenG, based on a network metaanalysis. Adverse events, utility values, and costs were obtained from published literature. The model estimated life-years gained, quality-adjusted life-years (QALYs) gained, and costs. The time horizon was 20 years, with a cycle time of 28 days. Outcomes and costs were discounted at 3.0% per year, and costs were estimated from a US health care payer perspective. One-way and probabilistic sensitivity analyses were conducted. RESULTS: In this cross-trial analysis of unfit CLL patients, in the base case, VenG had lower projected total costs than all comparators investigated. VenG also had larger projected health benefits (more QALYs gained) than GClb, BR, Ibr, and Ibr + R. VenG was therefore more effective and less costly than these comparators (dominant). Ibr + G, Acala, and Acala + G showed higher QALYs gained vs VenG (0.022, 0.672, and 0.961, respectively), and substantially higher projected costs vs VenG ($1,488,400, $1,579,737, and $1,656,154, respectively). Thus, Ibr + G, Acala, and Acala + G would cost more than $1,000,000 per QALY gained vs VenG. At the commonly used willingness-to-pay threshold of $150,000 per QALY gained, Ibr + G, Acala, and Acala + G were not cost-effective compared with VenG. CONCLUSIONS: Fixed-duration VenG for 12 months is a cost-effective first-line treatment option for unfit CLL patients compared with other available options and provides value for money to US health care payers at a threshold of $150,000 per QALY gained. Future studies with longer trial follow-up and more mature survival data may help to confirm longer-term cost benefits of VenG. DISCLOSURES: Genentech Inc. and AbbVie provided financial support for this study. Genentech Inc., AbbVie, and Pharmerit - An OPEN Health Company participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the manuscript. Venetoclax is being developed in a collaboration between Genentech Inc. and AbbVie. Ravelo and Shapouri are employed by Genentech Inc. and have ownership interests. Manzoor and Sail are employed by AbbVie and have ownership interests. Chatterjee, van de Wetering, and Qendri, employees of Pharmerit - An OPEN Health Company, received consultancy fees from AbbVie. Davids has received consultancy fees from AbbVie, AstraZeneca, Eli Lilly, Genentech Inc., Janssen, MEI Pharma, Novartis, Pharmacyclics, and Verastem; research funding from Ascentage Pharma, Genentech Inc., MEI Pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, and Verastem; and has served on board of directors or advisory committees for AbbVie, Adaptive Biotechnologies, AstraZeneca, BeiGene, Eli Lilly, Genentech Inc., Janssen, Pharmacyclics, TG Therapeutics, and Verastem. This study was presented as a poster at ASH 61st Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL.

Evaluation of the Novel 4R Oncology Care Planning Model in Breast Cancer: Impact on Patient Self-Management and Care Delivery in Safety-Net and Non-Safety-Net Centers.

PURPOSE: Optimal cancer care requires patient self-management and coordinated timing and sequence of interdependent care. These are challenging, especially in safety-net settings treating underserved populations. We evaluated the 4R Oncology model (4R) of patient-facing care planning for impact on self-management and delivery of interdependent care at safety-net and non-safety-net institutions. METHODS: Ten institutions (five safety-net and five non-safety-net) evaluated the 4R intervention from 2017 to 2020 with patients with stage 0-III breast cancer. Data on self-management and care delivery were collected via surveys and compared between the intervention cohort and the historical cohort (diagnosed before 4R launch). 4R usefulness was assessed within the intervention cohort. RESULTS: Survey response rate was 63% (422/670) in intervention and 47% (466/992) in historical cohort. 4R usefulness was reported by 79.9% of patients receiving 4R and was higher for patients in safety-net than in non-safety-net centers (87.6%, 74.2%, P = .001). The intervention cohort measured significantly higher than historical cohort in five of seven self-management metrics, including clarity of care timing and sequence (71.3%, 55%, P < .001) and ability to manage care (78.9%, 72.1%, P = .02). Referrals to interdependent care were significantly higher in the intervention than in the historical cohort along all six metrics, including primary care consult (33.9%, 27.7%, P = .045) and flu vaccination (38.6%, 27.9%, P = .001). Referral completions were significantly higher in four of six metrics. For safety-net patients, improvements in most self-management and care delivery metrics were similar or higher than for non-safety-net patients, even after controlling for all other variables. CONCLUSION: 4R Oncology was useful to patients and significantly improved self-management and delivery of interdependent care, but gaps remain. Model enhancements and further evaluations are needed for broad adoption. Patients in safety-net settings benefited from 4R at similar or higher rates than non-safety-net patients, indicating that 4R may reduce care disparities.

Real-World Assessment of Patient Care and Practice Efficiency With the Introduction of Subcutaneous Rituximab.

INTRODUCTION: A subcutaneous (SC) formulation of the anti-CD20 monoclonal antibody, rituximab (Rituxan), is approved in diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). Rituximab-SC (R-SC) has been associated with time and clinic resource savings vs the original intravenous formulation (R-IV). Insight into the resource implications of widening R-SC adoption in a US oncology setting is needed. METHODS: A single-institution, retrospective observational analysis was conducted in adult patients with DLBCL, FL, or CLL. The primary outcome measure was chair occupancy time (difference between patient room-in and room-out times). Prescribing patterns were a secondary outcome. RESULTS: Overall, 1190 patients were analyzed (treatment time frame: pre-R-SC adoption: n = 490 [41%], pre- and post R-SC adoption: n = 189 [16%], post R-SC adoption: n = 511 [43%]). Of the patients in the post-R-SC period, 374 (73%) received R-IV, 52 (10%) received R-IV and R-SC, and 85 (17%) received R-SC. When administered, R-SC reduced combination therapy chair time vs R-IV by a mean 37% (93.2 minutes; P < .001). Monotherapy (any route) reduced chair time vs combination by a mean 35.2 minutes (P < .001), with a further 40.2-minute reduction with R-SC (P < .001), a 62% (133.4-minute) total chair time savings vs R-IV. Doctors were more likely to prescribe R-SC to patients with FL than DLBCL. CONCLUSIONS: R-SC is associated with significantly reduced chair time vs R-IV in a US oncology setting. Widespread adoption would be expected to improve practice efficiency and patient access to care, and to reduce health care resource burden.

Budget Impact of 12-Month Fixed Treatment Duration Venetoclax in Combination with Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia Patients in the United States.

OBJECTIVES: This study aimed to assess the total cost of care (TCC) and budget impact of introducing 12-month fixed duration venetoclax + obinutuzumab (VEN+G) as first-line treatment for chronic lymphocytic leukemia (CLL) from the perspective of a US health plan with 1,000,000 (1M) members. METHODS: The 3-year model included the following comparators: fludarabine + cyclophosphamide + rituximab (FCR), bendamustine + rituximab (BR), obinutuzumab + chlorambucil (GClb), ibrutinib (Ibr), and Ibr+Rituximab/obinutuzumab [Ibr+R/Ibr+G]). TCC included US-specific costs associated with treatment (i.e., drug, administration, and wastage), adverse events, routine care, and monitoring. Dosing and safety data were drawn from clinical trials and US package inserts. Budget impact outcomes were presented on an absolute and per-member per-month (PMPM) basis. Sensitivity analyses explored uncertainty in influential parameters, including scenarios testing the duration of treat-to-progression agents. RESULTS: Over the 3-year time horizon, introducing VEN+G in a 1M-member health plan resulted in total cost savings of $1,550,663 (PMPM - $0.04), compared to a scenario without VEN+G. The fixed 12-month duration of VEN+G contributed to this cost saving by reducing cumulative treatment costs compared with Ibr-based regimens. By year 3, the cumulative difference in TCC of VEN+G compared with Ibr, Ibr+G, and Ibr+R amounted to - $300,942, - $367,001, and - $369,784, respectively. Extensive sensitivity analyses supported the base case findings. CONCLUSIONS: Introducing VEN+G among first-line CLL treatments to a US health plan resulted in cost savings compared to a plan with chemoimmunotherapies and Ibr-based therapies only. Economic benefits of VEN+G, a novel agent with fixed treatment duration, coupled with proven clinical benefits should help inform formulary adoption decisions and treatment recommendations.

Bevacizumab at first recurrence after standard radio-chemotherapy is associated with improved overall survival in glioblastoma patients with large tumor burden.

BACKGROUND: Since its approval for use in recurrent glioblastoma (GBM), the survival benefit of bevacizumab (Bev) remains to be demonstrated. To address this issue, we retrospectively examined survival from first recurrence in patients treated with Bev, lomustine (CCNU), or Bev/CCNU. METHODS: We identified 168 primary GBM patients diagnosed at UCLA and Kaiser Permanente LA who received upfront radio-chemotherapy, followed by Bev and/or CCNU at first recurrence. Three patient groups, contemporaneously diagnosed from 2009 through 2015, were identified: (1) patients treated with Bev alone (n = 49), (2) CCNU alone (CCNU 09-15) (n = 36), and (3) Bev/CCNU (n = 53). Another CCNU control group (n = 30) diagnosed from 2001 through 2004 (CCNU 01-04) was also derived. We measured tumor size at first recurrence treatment initiation, using bidimensional (2D) and volumetric (3D) techniques, and analyzed overall survival (OS) from first recurrence. RESULTS: Among the entire cohort, larger tumor size at first recurrence was associated with poorer survival. The CCNU 01-04 group had similar tumor size as the Bev arms and low Bev crossover (7%). Treatment with Bev was associated with improved survival in patients with large tumor 2D measurements: Median OS for Bev and Bev/CCNU groups were 6.71 mo (n = 27) and 6.97 mo (n = 36) vs 4.03 mo (n = 10) in CCNU 01-04. Analysis by 3D measurement yielded similar results. Interestingly, the CCNU 09-15 group showed the highest survival, likely due to smaller tumor size and crossover to Bev (69%). CONCLUSION: Survival advantage from Bev treatment was observed only among patients with large tumor burden as determined by either 2D or 3D measurement.

Single-institution retrospective review of patients with recurrent glioblastoma treated with bevacizumab in clinical practice.

BACKGROUND AND AIMS: This retrospective review of patients with recurrent glioblastoma treated at the Preston Robert Tisch Brain Tumor Center investigated treatment patterns, survival, and safety with bevacizumab in a real-world setting. METHODS: Adult patients with glioblastoma who initiated bevacizumab at disease progression between January 1, 2009, and May 14, 2012, were included. A Kaplan-Meier estimator was used to describe overall survival (OS), progression-free survival (PFS), and time to greater than or equal to 20% reduction in Karnofsky Performance Status (KPS). The effect of baseline demographic and clinical factors on survival was examined using a Cox proportional hazards model. Adverse event (AE) data were collected. RESULTS: Seventy-four patients, with a median age of 59 years, were included in this cohort. Between bevacizumab initiation and first failure, defined as the first disease progression after bevacizumab initiation, biweekly bevacizumab and bevacizumab/irinotecan were the most frequently prescribed regimens. Median duration of bevacizumab treatment until failure was 6.4 months (range, 0.5-58.7). Median OS and PFS from bevacizumab initiation were 11.1 months (95% confidence interval [CI], 7.3-13.4) and 6.4 months (95% CI, 3.9-8.5), respectively. Median time to greater than or equal to 20% reduction in KPS was 29.3 months (95% CI, 13.8-∞). Lack of corticosteroid usage at the start of bevacizumab therapy was associated with both longer OS and PFS, with a median OS of 13.2 months (95% CI, 8.6-16.6) in patients who did not initially require corticosteroids versus 7.2 months (95% CI, 4.8-12.5) in those who did (P = 0.0382, log-rank), while median PFS values were 8.6 months (95% CI, 4.6-9.7) and 3.7 months (95% CI, 2.7-6.6), respectively (P = 0.0243, log-rank). Treatment failure occurred in 70 patients; 47 of whom received salvage therapy, and most frequently bevacizumab/carboplatin (7/47; 14.9%). Thirteen patients (18%) experienced a grade 3 AE of special interest for bevacizumab. CONCLUSIONS: Treatment patterns and outcomes for patients with recurrent glioblastoma receiving bevacizumab in a real-world setting were comparable with those reported in prospective clinical trials.

Cost of Disease Progression in Patients with Metastatic Breast, Lung, and Colorectal Cancer.

INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are piloting value-based and episodic or bundled-care payment models in oncology. Disease progression and associated costs may affect these models, particularly if such programs do not account for disease severity and progression risk across patient populations. This study estimated the incremental cost of disease progression in patients diagnosed with metastatic breast cancer (mBC), colorectal cancer (mCRC) and lung cancer (mLC) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of mBC, mCRC, and mLC and systemic antineoplastic agent use from July 1, 2006, to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 5,709 patients with mBC, 3,707 patients with mCRC, and 5,201 patients with mLC, 56.8% of patients with mBC, 58.1% of those with mCRC, and 80.3% of those with mLC patients had evidence of disease progression over 12 months. Among patients with mBC and mCRC, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, which accounted for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with mBC, mCRC, and mLC. In each of the three cancer types, delays in progression were associated with lower health care costs. CONCLUSION: Progression of mLC, mBC, and mCRC was associated with higher health care costs over a 12-month period. Delayed cancer progression was associated with substantial cost reductions in patients with each of the three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with solid tumor cancers are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with lung cancer, breast cancer, and colorectal cancer and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in our study quantify the economic value of delaying or preventing disease progression and may inform payers and physician groups about value-based payment programs.

Cost of Disease Progression in Patients with Chronic Lymphocytic Leukemia, Acute Myeloid Leukemia, and Non-Hodgkin's Lymphoma.

INTRODUCTION: To reduce health care costs and improve care, payers and physician groups are switching to quality-based and episodic or bundled-care models. Disease progression and associated costs may affect these models, particularly if such programs do not account for differences in disease severity and progression risk within the cohort. This study estimated the incremental cost of disease progression in patients diagnosed with chronic lymphoid leukemia (CLL), acute myeloid leukemia (AML), and non-Hodgkin's lymphoma (NHL) and compared costs among patients with and without progression. METHODS: This was a retrospective study using U.S. administrative claims data from commercial and Medicare Advantage health care enrollees with evidence of CLL, AML, and NHL and systemic antineoplastic agent use from July 1, 2006 to August 31, 2014. Outcome measures included disease progression, 12-month health care costs, and 3-year cumulative predictive health care costs. RESULTS: Of 1,056 patients with CLL, 514 patients with AML, and 7,601 patients with NHL, 31.1% of patients with CLL, 63.8% of those with AML, and 36.9% of those with NHL had evidence of disease progression. Among patients with CLL and NHL, adjusted and unadjusted health care costs were significantly higher among progressors versus nonprogressors. Per-patient-per-month costs, accounting for variable follow-up time, were almost twice as high among progressors versus nonprogressors in patients with CLL, AML, and NHL. In each of the three cancer types, the longer disease progression was delayed, the lower the health care costs. CONCLUSION: Progression of CLL, AML, and NHL was associated with higher health care costs over a 12-month period. Delaying cancer progression resulted in a substantial cost reduction in patients with all three cancer types. IMPLICATIONS FOR PRACTICE: Data on the rates and incremental health care costs of disease progression in patients with hematologic malignancies are lacking. This study estimated the incremental costs of disease progression in patients diagnosed with chronic lymphocytic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma and compared health care costs in patients with and without evidence of disease progression in a real-world population. The data obtained in this study will assist future studies in quantifying the cost impact of decreased progression rates and will inform payers and physician groups about setting rates for episode and bundled payment programs.

Oncologists' Perceptions of Drug Affordability Using NCCN Evidence Blocks: Results from a National Survey.

BACKGROUND: The increasing prevalence of cancer coupled with approvals of new drugs and technologies used in therapy have brought increased scrutiny to the cost and value of treatments in oncology. To address the rising concern about oncology drug costs, several organizations have developed value frameworks to help assess the value of oncology regimens. The objective of this study was to assess oncologists' perceptions, awareness, and knowledge of all oncology value frameworks in the United States and to understand oncologists' perceptions of affordability in the context of National Comprehensive Cancer Network (NCCN) Evidence Blocks. OBJECTIVES: To (a) assess oncologists' awareness, knowledge, perceptions, and ratings of the American Society of Clinical Oncology Value Framework (AVF), the Institute for Clinical and Economic Review (ICER) value framework, NCCN Evidence Blocks, and Memorial Sloan Kettering Cancer Center's DrugAbacus; (b) assess oncologists' knowledge and perceptions of drug affordability as defined by the NCCN Evidence Blocks methodology; and (c) determine the factors that influence drug affordability ratings. METHODS: Data were collected from an electronic cross-sectional survey of 200 U.S.-based oncologists from a variety of practice settings. Oncologists were asked about their knowledge and perceptions of 4 value frameworks-NCCN Evidence Blocks, AVF, the ICER value framework, and DrugAbacus. Using NCCN Evidence Blocks, oncologists were asked to rate a variety of hypothetical cancer therapies and assign costs (in U.S. dollars) to the 5 levels of affordability. Additional questions that assessed perceived patient out-of-pocket (OOP) costs and comfort level in assessing affordability were also included in the survey. RESULTS: Oncologists were most familiar with NCCN Evidence Blocks (90%), followed by the AVF (84%), ICER value framework (57%), and DrugAbacus (56%). Oncologists rated affordability higher (mean rating 3: moderately expensive) versus the actual NCCN panel affordability rating (mean rating 1: very expensive). The affordability rating was similar across a variety of hypothetical cancer therapies and tumor types (rating: 3). Oncologists estimated the costs for this rating of 3 to range from $4,600 to $6,000 per month, which was inconsistent with actual drug costs. Oncologists estimated the mean monthly OOP costs for patients with insurance to range from $1,260 for a new oral medication to $1,700 for a new infused medication. Only 26% of oncologists were comfortable or very comfortable with rating costs associated with affordability levels. CONCLUSIONS: Surveyed oncologists rated cancer therapies as more affordable (per NCCN Evidence Blocks criteria) than NCCN panel ratings. Costs associated with affordability were not consistent with actual treatment costs; however, most oncologists were not comfortable with rating affordability. Patient OOP costs had the biggest influence on affordability ratings; however, physicians overestimated patient OOP costs significantly. There is an opportunity to improve the value frameworks, especially with regard to affordability assessment. DISCLOSURES: This study was funded by Genentech. Shah-Manek is employed by Ipsos Healthcare, a health care consulting company that received funding from Genentech to conduct this study. DiBonaventura was employed by Ipsos Healthcare at the time of this study. Wong and Ravelo are employed by Genentech. Shah-Manek has consulted with Genentech, Merck, Alkermes, Avanis, Alnylam, Novo Nordisk, Teva, Lilly, and BMS. This work was presented as an oral presentation at the ASCO 2017 Annual Meeting in Chicago, Illinois, on June 2-6, 2017.

Effect of Brain Metastasis on Patient-Reported Outcomes in Advanced NSCLC Treated in Real-World Community Oncology Settings.

INTRODUCTION: Health-related quality of life (HRQOL) in advanced non-small-cell lung cancer (NSCLC) might be affected by the presence of brain metastasis (BM). We report findings from a prospective observational study that examined HRQOL in patients newly diagnosed with advanced NSCLC, with or without baseline BM, through 1 year of follow-up. PATIENTS AND METHODS: Patients starting first-line treatment of stage IIIB/IV NSCLC were prospectively enrolled and consented at 34 US-based community oncology practices. Data on patient-reported outcomes (PROs) were collected once per cycle during treatment, and at each visit after discontinuation. PROs included the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30) and Lung Cancer Module (QLQ-LC13), the Lung Cancer Module of the M.D. Anderson Symptom Inventory (MDASI-LC), and the Rotterdam Activity Level Scale (RALS). Linear mixed models were used to examine the effect of baseline BM, including differences in change over time. RESULTS: One hundred forty-five patients provided follow-up PRO data, comprising 1100 individual surveys and 32 PRO end points. The patient group was 58.6% (n = 85) male, and 86.2% (n = 125) Caucasian. Patients with baseline BM were younger (61.3 vs. 65.8 years; P = .040) with more concurrent radiotherapy (59.4% [n = 19] vs. 15.9% [n = 18]; P < .0001). Results showed minimal differences in baseline HRQOL. Of the 20 measures that showed significant group differences in HRQOL over time, 18 showed greater deterioration for patients with baseline BM. These 18 measures included all QLQ-C30 composite measures except Global Health Status, all MDASI-LC measures, and the RALS (all P < .05). For these measures, the average 1-year deterioration in patients with baseline BM was 19.4%. CONCLUSION: Newly diagnosed advanced NSCLC patients with baseline BM experienced a significantly faster and clinically meaningful deterioration in PRO-based HRQOL compared with those without baseline BM.

Overall survival in patients with glioblastoma before and after bevacizumab approval.

OBJECTIVE: Glioblastoma (GBM) is an aggressive disease with limited therapeutic options. While bevacizumab was approved in 2009 for the treatment of patients with progressive GBM, its impact on overall survival (OS) remains unclear. Using US population-based cancer registry data (SEER), this study compared OS of patients diagnosed with GBM before and after bevacizumab approval. METHODS: Adult patients from SEER with a GBM diagnosis were divided into two cohorts: patients diagnosed in 2006-2008 (pre-bevacizumab cohort, n = 6,120) and patients diagnosed in 2010-2012 (post-bevacizumab cohort, n = 6,753). Patients were included irrespective of the treatments received. OS post-diagnosis was compared between the study cohorts utilizing Kaplan-Meier analyses and multivariate Cox proportional hazards regression. RESULTS: Among 12,873 patients with GBM, the median age was 62 years, 41% were women, 31% underwent gross total resection, and 75% received radiation therapy. Survival was stable within the 2006-2008 period (median survival = 9 months for each year), but increased after year 2009 (median survival = 10 and 11 months for years 2010/2011 and 2012, respectively). The adjusted hazard of death was significantly lower in the post-bevacizumab approval cohort (hazard ratio = 0.91, p < .01). CONCLUSIONS: The results of this large population-based study suggested an improvement in OS among patients with a GBM diagnosis in 2010-2012 compared to 2006-2008. While the cause of this improvement cannot be proven in a retrospective analysis, the timing of the survival increase coincides with the approval of bevacizumab for the treatment of patients with progressive GBM, indicating a possible benefit of bevacizumab in this population.

Effectiveness outcomes and health related quality of life impact of disease progression in patients with advanced nonsquamous NSCLC treated in real-world community oncology settings: results from a prospective medical record registry study.

BACKGROUND: Treatment options for advanced nonsquamous non-small cell lung cancer (NSCLC) in the first line include platinum-based doublet therapy with or without bevacizumab. This study examined efficacy outcomes and patient reported outcomes (PROs) in a community oncology patient sample. METHODS: Advanced nonsquamous NSCLC patients from 34 U.S. community oncology practices treated in first line with bevacizumab regimens (A platinum doublet; gemcitabine doublet; pemetrexed with platinum) or non-bevacizumab regimens (B platinum doublet; gemcitabine doublet; C pemetrexed with platinum) were recruited for this prospective study. Patient characteristics and clinical outcomes were accessed from routine care records. Three validated and widely used PRO measures of health related quality of life (HRQOL) and symptom burden were collected prospectively at each visit and up to one-year follow-up. Effectiveness outcomes were progression free survival (PFS) and overall survival (OS) assessed by Kaplan-Meier and Cox regression methods. PROs were analyzed with linear mixed model regression to examine changes over time, and the effect of disease progression. RESULTS: Of 147 patients in the study, 145 provided PRO data. Patients in treatment groups were: A (n = 66, 44.9%); B (n = 25, 17.0%); C (n = 56, 38.1%). A was associated with significantly longer OS than B (HR = 0.341, p = 0.0012), and significantly longer than C (HR = 0.602, p = 0.0354). PFS results were similar. Irrespective of regimen group and on 12/32 measures, patients showed significant and clinically meaningful worsening of symptoms and HRQOL at disease progression. After disease progression, the pattern of symptom and HRQOL change showed continued worsening. CONCLUSIONS: Bevacizumab-containing regimens were associated with longer PFS and OS compared with non-bevacizumab regimens. PRO measures show disease progression is associated with worsening HRQOL. Delaying disease progression can sustain better HRQL and reduce symptom burden.

Access to Cancer Specialist Care and Treatment in Patients With Advanced Stage Lung Cancer.

BACKGROUND: Access to specialty care is critical for patients with advanced stage lung cancer. This study assessed access to cancer specialists and cancer treatment in a broad population of patients with advanced stage lung cancer. MATERIALS AND METHODS: Two study samples were extracted from 2 claims databases and analyzed independently: patients aged ≥ 18 years with de novo diagnosis of metastatic lung cancer in the MarketScan database between 2008 and 2014 (commercially insured adult patients; n = 22,268); and patients aged ≥ 65 years in the Surveillance, Epidemiology, and End Results-Medicare database with a diagnosis of advanced non-small-cell lung cancer between 2007 and 2011 (Medicare-insured elderly patients; n = 9651). The study period spanned from 6 weeks before the first lung biopsy tied to the initial lung cancer diagnosis until the end of continuous health insurance enrollment, or data availability, or death. RESULTS: Among the commercially insured adults (MarketScan), most patients were seen by a cancer specialist within a month of first lung biopsy (80%), 12% were never seen by a cancer specialist, and 6% did not receive cancer-directed therapy. Among the Medicare-insured elderly patients (SEER-Medicare), the proportions were 79%, 4%, and 10%, respectively. Patients seen by a cancer specialist were more likely to receive cancer-directed therapy (95% vs. 92%, P < .001 and 92% vs. 38%, P < .001, respectively). CONCLUSION: Between 4% and 12% of patients with advanced stage lung cancer do not have appropriate access to cancer specialist, which appears to negatively affect access to optimal and timely treatment.

Survival Gains from First-Line Systemic Therapy in Metastatic Non-Small Cell Lung Cancer in the U.S., 1990-2015: Progress and Opportunities.

BACKGROUND: Approximately 190,000 Americans are diagnosed with non-small cell lung cancer (NSCLC) annually, and about half have metastatic (Stage IV) disease. These patients have historically had poor survival prognosis, but several new therapies introduced since 2000 provide options for improved outcomes. The objectives of this study were to quantify survival gains from 1990, when best supportive care (BSC) only was standard, to 2015 and to estimate the impact of expanded use of systemic therapies in clinically appropriate patients. MATERIALS AND METHODS: We developed a simulation model to estimate survival gains for patients with metastatic NSCLC from 1990-2015. Survival estimates were derived from major clinical trials and extrapolated to a lifetime horizon. Proportions of patients receiving available therapies were derived from the Surveillance, Epidemiology, and End Results database and a commercial treatment registry. We also estimated gains in overall survival (OS) in scenarios in which systemic therapy use increased by 10% and 30% relative to current use. RESULTS: From 1990-2015, one-year survival proportion increased by 14.1% and mean per-patient survival improved by 4.2 months (32,700 population life years). Increasing treated patients by 10% or 30% increased OS by 5.1 months (39,700 population life years) and 6.9 months (53,800 population life years), respectively. CONCLUSION: Although survival remains poor in metastatic NSCLC relative to other common cancers, meaningful progress in per-patient and population-level outcomes has been realized over the past 25 years. These advances can be improved even further by increasing use of systemic therapies in the substantial proportion of patients who are suitable for treatment yet who currently receive BSC only. The Oncologist 2017;22:304-310 IMPLICATIONS FOR PRACTICE: Approximately 93,500 Americans are diagnosed with metastatic non-small cell lung cancer (NSCLC) annually. Historically, these patients have had poor survival prognosis, but newer therapies provide options for improved outcomes. This simulation modeling study quantified metastatic NSCLC survival gains from 1990-2015. Over this period, the one-year survival proportion and mean per-patient survival increased by 14.1% and 4.2 months, respectively. Though metastatic NSCLC survival remains poor, the past 25 years have brought meaningful gains. Additional gains could be realized by increasing systemic therapy use in the substantial proportion of patients who are suitable for treatment, yet currently receive only supportive care.

First-Line Treatment with Bevacizumab and Platinum Doublet Combination in Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Cohort Study in US Oncology Community Practices.

BACKGROUND: Real-world evidence is lacking on the impact of bevacizumab added to carboplatin/paclitaxel (Bev + CP) therapy versus CP alone for patients with non-squamous non-small cell lung cancer (NS-NSCLC), particularly in those excluded from clinical trials. METHODS: This is a retrospective electronic medical record analysis of patients who received first-line therapy with Bev + CP or CP between 1 October 2006 and 30 June 2013. We identified four subsets: elderly patients (≥65 years), patients with brain/central nervous system (CNS) metastases, patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2, and patients receiving anticoagulation. We used descriptive statistics to describe patient characteristics and treatment patterns and evaluated progression-free survival (PFS) and overall survival (OS) using survival analyses. RESULTS: The study included 431 patients (Bev + CP: 231; CP: 200). The Bev + CP cohort was more likely to receive four or more cycles of induction therapy (72 vs. 50 %) and was more likely to receive maintenance therapy (45 vs. 21 %) than patients receiving CP. In the overall population, median PFS and OS were significantly longer in the Bev + CP cohort than in the CP cohort: 6.7 vs. 5.1 months (hazard ratio [HR] 0.74; 95 % confidence interval [CI] 0.59-0.92; p = 0.008) and 11.9 vs. 9.0 months (HR 0.57; 95 % CI 0.44-0.73; p < 0.001), respectively. Treatment with Bev + CP in patients aged ≥65 years and in those with brain/CNS metastases was also associated with a significant risk reduction in PFS (35 and 51 %, respectively; p < 0.05 for both) and OS (46 and 62 %, respectively; p < 0.05 for both) compared with CP alone. CONCLUSION: Bev + CP is associated with a significant improvement in PFS and OS in patients with NS-NSCLC and in subsets with brain/CNS metastases and those aged ≥65 years.

Health-Related Quality of Life in a Randomized Phase III Study of Bevacizumab, Temozolomide, and Radiotherapy in Newly Diagnosed Glioblastoma.

PURPOSE: As glioblastoma progresses, patients experience a decline in health-related quality of life (HRQoL). Delaying this decline is an important treatment goal. In newly diagnosed glioblastoma, progression-free survival was prolonged when bevacizumab was added to radiotherapy plus temozolomide (RT/TMZ) versus placebo plus RT/TMZ (phase III AVAglio study; hazard ratio, 0.64; 95% CI, 0.55 to 0.74; P < .001). To ensure that addition of bevacizumab to standard-of-care therapy was not associated with HRQoL detriment, HRQoL assessment was a secondary objective. PATIENTS AND METHODS: Patients completed European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and BN20 at each tumor assessment (Appendix Table A1, online only). Raw scores were converted to a 100-point scale and mean changes from baseline scores were evaluated (stable: < 10-point change; clinically relevant deterioration/improvement: ≥ 10-point change). Deterioration-free survival was the time to deterioration/progression/death; time to deterioration was the time to deterioration/death. RESULTS: Most evaluable patients who had not progressed (> 74%) completed all HRQoL assessments for at least 1 year of treatment, and almost all completed at least one HRQoL assessment at baseline (98.3% and 97.6%, bevacizumab and placebo arms, respectively). Mean changes from baseline did not reach a clinically relevant difference between arms for most items. HRQoL declined at progression in both arms. The addition of bevacizumab to RT/TMZ resulted in statistically longer (P < .001) deterioration-free survival across all items. Time to deterioration was not statistically longer in the placebo plus RT/TMZ arm (v bevacizumab) for any HRQoL item. CONCLUSION: The addition of bevacizumab to standard-of-care treatment for newly diagnosed glioblastoma had no impact on HRQoL during the progression-free period.