Real-world total cost of care by line of therapy in relapsed/refractory diffuse large B-cell lymphoma.

AIMS: There are multiple recently approved treatments and a lack of clear standard-of-care therapies for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). While total cost of care (TCC) by the number of lines of therapy (LoTs) has been evaluated, more recent cost estimates using real-world data are needed. This analysis assessed real-world TCC of R/R DLBCL therapies by LoT using the IQVIA PharMetrics Plus database (1 January 2015-31 December 2021), in US patients aged ≥18 years treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or an R-CHOP-like regimen as first-line therapy. METHODS: Treatment costs and resources in the R/R setting were assessed by LoT. A sensitivity analysis identified any potential confounding of the results caused by the impact of the COVID-19 pandemic on healthcare utilization and costs. Overall, 310 patients receiving a second- or later-line treatment were included; baseline characteristics were similar across LoTs. Inpatient costs represented the highest percentage of total costs, followed by outpatient and pharmacy costs. RESULTS: Mean TCC per-patient-per-month generally increased by LoT ($40,604, $48,630, and $59,499 for second-, third- and fourth-line treatments, respectively). Costs were highest for fourth-line treatment for all healthcare resource utilization categories. Sensitivity analysis findings were consistent with the overall analysis, indicating results were not confounded by the COVID-19 pandemic. LIMITATIONS: There was potential misclassification of LoT; claims data were processed through an algorithm, possibly introducing errors. A low number of patients met the inclusion criteria. Patients who switched insurance plans, had insurance terminated, or whose enrollment period met the end of data availability may have had truncated follow-up, potentially resulting in underestimated costs. CONCLUSION: Total healthcare costs increased with each additional LoT in the R/R DLBCL setting. Further improvements of first-line treatments that reduce the need for subsequent LoTs would potentially lessen the economic burden of DLBCL.

Matching-adjusted indirect comparison from the Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence (LEO CReWE) study to a clinical trial of mosunetuzumab in relapsed or refractory follicular lymphoma.

Mosunetuzumab is a novel bispecific antibody targeting epitopes on CD3 on T cells and CD20 on B cells with the goal of inducing T-cell mediated elimination of malignant B cells. A recent pivotal phase I/II clinical trial (GO29781) demonstrated that mosunetuzumab induced an overall response rate of 80%, complete response rate of 60%, and a median progression-free survival of 17.9 months in patients with relapsed/refractory (r/r) follicular lymphoma (FL) following at least two prior lines of systemic therapy, including alkylator and anti-CD20 antibody-based therapy. Historical data from cohorts receiving therapy for r/r FL can provide some context for interpretation of single-arm trials. We compared the results from the mosunetuzumab trial to outcomes from a cohort of patients with r/r FL from the LEO Consortium for Real World Evidence (LEO CReWE). We applied clinical trial eligibility criteria to the LEO CReWE cohort and utilized matching-adjusted indirect comparison weighting to balance the clinical characteristics of the LEO CReWE cohort with those from the mosunetuzumab trial. Overall response rates (73%, 95% CI:65-80%) and complete response rates (53%, 95% CI:45-61%) observed in the weighted LEO CReWE cohort were lower than those reported on the mosunetuzumab trial (ORR=80%, 95% CI:70-88%; CR=60%, 95% CI:49-70% respectively). Progression-free survival at 12 months was similar in the weighted LEO CReWE (60%, 95% CI:51-69%) and the mosunetuzumab trial (PFS 58%, 95% CI:47-68%). Sensitivity analyses examining the impact of matching variables, selection of line of therapy, and application of eligibility criteria, provide context for best practices in this setting.

US cost-effectiveness analysis of polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma.

AIMS: We evaluated the pharmacoeconomic value of polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) in previously untreated diffuse large B-cell lymphoma (DLBCL) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: A 3-state partitioned survival model was used to estimate life years (LYs), quality-adjusted LYs (QALYs), and cost impacts of Pola-R-CHP versus R-CHOP. Analyses utilized mixture-cure survival modelling, assessed a lifetime horizon, discounted all outcomes at 3% per year, and examined both payer and societal perspectives. Progression-free survival, overall survival (OS), drug utilization, treatment duration, adverse reactions, and subsequent treatment inputs were based on data from the POLARIX study (NCT03274492). Costs included drug acquisition/administration, adverse reaction management, routine care, subsequent treatments, end-of-life care, and work productivity. RESULTS: Incremental cost-effectiveness ratios of Pola-R-CHP versus R-CHOP were $70,719/QALY gained and $88,855/QALY gained from societal and payer perspectives, respectively. The $32,824 higher total cost of Pola-R-CHP versus R-CHOP was largely due to higher drug costs ($122,525 vs $27,694), with cost offsets including subsequent treatment (-$52,765), routine care (-$1,781), end-of-life care (-$383), and work productivity (-$8,418). Pola-R-CHP resulted in an increase of 0.47 LYs and 0.46 QALYs versus R-CHOP. Pola-R-CHP was cost-effective in 60.9% and 58.0% of simulations at a willingness-to-pay threshold of $150,000/QALY gained from societal and payer perspectives, respectively. LIMITATIONS: There was uncertainty around the OS extrapolation in the model, and costs were derived from different sources. Recommended prophylactic medications were not included; prophylactic use of granulocyte colony-stimulating factor for all patients was assumed to be equal across treatment arms in POLARIX. Work productivity loss was estimated from a general population and was not specific to patients with DLBCL. CONCLUSION: Pola-R-CHP was projected to be cost-effective versus R-CHOP in previously untreated DLBCL, suggesting that Pola-R-CHP represents good value relative to R-CHOP in this setting.

Cost of Disease Progression in Diffuse Large B-Cell Lymphoma After Frontline Treatment With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone.

BACKGROUND: In recent years, novel agents have become available to treat relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the impact of such agents on treatment costs has not been formally studied. We present results from 2 independent, retrospective, real-world cohort analyses to determine the cost of disease progression after first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MATERIALS AND METHODS: Analyses were conducted using the IQVIA PharMetricsⓇ Plus claims database and the Surveillance, Epidemiology, and End Results registry-Medicare-linked database (SEER-Medicare) and included patients ≥18 years and ≥66 years, respectively. "No progression" was defined as no second-line therapy for ≥2 years after the end of first-line R-CHOP and "treated progression" as initiating a second-line therapy within 2 years following the end of first-line R-CHOP. Analyses were adjusted for baseline covariates, and per-patient-per-month (PPPM) costs were compared between progressors and nonprogressors. RESULTS: The IQVIA PharMetrics Plus analysis (January 1, 2010-June 30, 2018) included 871 patients (nonprogressors, n = 725; progressors, n = 146), including 10 patients who received chimeric antigen receptor T-cell therapy (CAR-T). Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,554 vs. $1561, P < .001). The SEER-Medicare analysis (January 1, 2010-December 31, 2017) included 4099 patients (nonprogressors, n = 3389; progressors, n = 710), including 12 patients receiving CAR-T. Treated progression was associated with significantly higher adjusted PPPM costs than no progression ($10,928 vs. $2902, P < .001). CONCLUSION: Treated progression of DLBCL increases adjusted PPPM costs by over $8000 compared with no progression.

Treatment patterns and outcomes of patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy (LEO CReWE): a multicentre cohort study.

BACKGROUND: Novel therapies for relapsed or refractory follicular lymphoma are commonly evaluated in single-arm studies without formal comparison with other treatments or historical controls. Consequently, rigorously defined treatment outcomes informing expectations for novel therapeutic strategies in this population are sparse. To inform outcome expectations, we aimed to describe treatment patterns, survival outcomes, and duration of response in patients with relapsed or refractory follicular lymphoma receiving three or more lines of systemic therapy. METHODS: In this multicentre cohort study, we developed a database of patients with relapsed or refractory follicular lymphoma from eight academic centres in the USA using data collected in the LEO Cohort study (NCT02736357) and the LEO Consortium. For this analysis, eligible patients were aged at least 18 years, had non-transformed grade 1-3a follicular lymphoma, and were receiving systemic therapy in the third line or later after previous therapy with an anti-CD20 antibody and an alkylating agent. Clinical data and patient outcomes were abstracted from medical records by use of a standard protocol. The index therapy for the primary analysis was defined as the first line of systemic therapy after the patient had received at least two previous systemic therapies that included an alkylating agent and an anti-CD20 therapy. The main endpoints of interest were overall response rate, progression-free survival, and overall survival. Outcomes were also evaluated in subsets of clinical interest (index therapy characteristics, patient and disease characteristics, treatment history, and best response assessment). FINDINGS: We screened 933 patients with follicular lymphoma, of whom 441 were included and diagnosed between March 6, 2002, and July 20, 2018. Index therapies included immunochemotherapy (n=133), anti-CD20 antibody monotherapy (n=53), lenalidomide with or without anti-CD20 (n=37), and phosphoinositide 3-kinase inhibitors with or without anti-CD20 (n=25). 57 (13%) of 441 patients received haematopoietic stem-cell transplantation and 98 (23%) of 421 patients with complete data received therapy on clinical trials. After a median follow-up of 71 months (IQR 64-79) from index therapy, 5-year overall survival was 75% (95% CI 70-79), median progression-free survival was 17 months (15-19), and the overall response rate was 70% (65-74; 280 of 400 patients evaluable for response). Patients who were refractory to therapy with an alkylating agent had a lower overall response rate (170 [68%] of 251 patients vs 107 [77%] of 139 patients) and a significantly lower 5-year overall survival (72%, 95% CI 66-78 vs 81%, 73-89; hazard ratio 1·60, 95% CI 1·04-2·46) than patients who were not refractory to therapy with an alkylating agent. INTERPRETATION: Patients with relapsed or refractory follicular lymphoma receive heterogeneous treatments in the third-line setting or later. We observed high response rates to contemporary therapies that were of short duration. These data identify unmet needs among patients with follicular lymphoma, especially those who are refractory to alkylating agents, and might provide evidence by which clinical trials evaluating novel treatments could be assessed. FUNDING: Genentech and the National Cancer Institute.

Improvements in Health-related Quality of Life and Symptoms in Patients With Previously Untreated Chronic Lymphocytic Leukemia: Final Results From the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine.

BACKGROUND: We evaluated health-related quality of life (HRQoL) in patients with chronic lymphocytic leukemia (CLL) receiving first-line chemoimmunotherapy in the GIBB single-arm, Phase II study of obinutuzumab plus bendamustine (BG). MATERIALS AND METHODS: Patients received six 28-day cycles of BG and were followed for up to 27 months. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (EORTC QLQ-C30) and EORTC QLQ Chronic Lymphocytic Leukemia 16 (QLQ-CLL16) questionnaires. Scores were linear-transformed to a 100-point scale, with clinically meaningful responses defined as a ≥ 10-point change from baseline. RESULTS: The patient-reported outcome (PRO) population comprised 98 patients (68.4% male; median age 61 years). EORTC QLQ-C30 global health status improvements were noted at all follow-up visits and were clinically meaningful 2 to 3 months after induction and at 3- and 27-months' follow-up. Clinically meaningful improvements were also observed for the EORTC QLQ-C30 role functioning, emotional functioning, fatigue and insomnia scales and the EORTC QLQ-CLL16 fatigue, disease symptoms and future health worries scales. Global health status was maintained throughout follow-up, and no clinically relevant deterioration in other HRQoL parameters was observed. CONCLUSION: PRO data from the GIBB study show improved overall HRQoL in patients with CLL who received first-line chemoimmunotherapy with BG.

Cost-effectiveness of obinutuzumab versus rituximab biosimilars for previously untreated follicular lymphoma.

BACKGROUND: In the randomized phase 3 GALLIUM trial, first-line treatment with obinutuzumab (GA101; G) plus chemotherapy (G + chemo) resulted in superior progression-free survival (PFS) compared with rituximab plus chemotherapy (R + chemo) for patients with follicular lymphoma (FL). G + chemo was found to be cost-effective when compared with R + chemo (incremental cost-effectiveness ratio [ICER] of approximately $2,300 per quality-adjusted life-year [QALY] gained). Two rituximab biosimilars, rituximab-abbs (Ra) and rituximab-pvvr (Rp), have been approved by the FDA for use in this setting. However, the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo has not yet been estimated. OBJECTIVE: To evaluate the cost-effectiveness of G + chemo versus Ra + chemo and Rp + chemo in the first-line treatment of FL. METHODS: We adapted an existing Markov model that compared G + chemo with R + chemo, using investigator-assessed PFS and postprogression survival data from the GALLIUM trial to model overall survival. All patients in the study received induction chemoimmunotherapy with either G + chemo or R + chemo, with responders then receiving obinutuzumab or rituximab maintenance therapy for 2 years or until disease progression. We assumed that the efficacy and safety of the rituximab biosimilars plus chemotherapy were the same as the R + chemo arm of the GALLIUM study. Drug utilization and treatment duration were also derived from GALLIUM. Health care costs were based on Medicare reimbursements, and drug costs were average sale prices for intravenous therapies or wholesale acquisition costs for oral therapies used after progression. Utility estimates were based on the GALLIUM trial data and published literature. Sensitivity analyses were conducted to assess the key drivers of the model and uncertainty in the results. Results: Treatment with G + chemo led to an increase of 0.93 QALYs relative to rituximab biosimilars plus chemotherapy (95% credible range [CR] = 0.36-1.46). The total cost of G + chemo was $191,317, whereas the total costs of Ra + chemo and Rp + chemo were $164,340 (Δ14.1%) and $169,755 (Δ11.3%), respectively, with G + chemo resulting in incremental costs of $26,978 (95% CR = $19,781-$33,119) and $21,562 (95% CR = $14,473-$28,389), respectively. The incremental total drug and administration costs were $32,678 (Δ25.4%) and $27,263 (Δ21.2%) for G + chemo versus Ra + chemo and G + chemo versus Rp + chemo, respectively. There were cost savings of $7,050 (Δ-12.4%) related to disease progression for G + chemo ($56,727) compared with Ra + chemo and Rp + chemo ($63,777). ICERs were $28,879 and $23,082 per QALY gained for G + chemo versus Ra + chemo and Rp + chemo, respectively. In probabilistic sensitivity analyses, G + chemo was cost-effective at the $50,000 and $100,000 per QALY thresholds versus both Ra + chemo (88% and 98% probabilities of cost-effectiveness, respectively) and Rp + chemo (93% and 98%, respectively). CONCLUSIONS: G + chemo is projected to be cost-effective versus rituximab biosimilars plus chemotherapy in the United States as first-line treatment for FL, driven by increased QALYs for G + chemo and cost savings from delayed disease progression. DISCLOSURES: This study was funded by Genentech, a member of the Roche Group. The study sponsor was involved in study design, data interpretation, and writing of the report. All authors approved the decision to submit the report for publication. Spencer and Guzauskas report fees from Genentech during the conduct of the study. Felizzi was employed by F. Hoffmann-La Roche at the time this study was conducted; Launonen is an employees of F. Hoffmann-La Roche. Felizzi and Launonen previously had share ownership in Novartis. Dawson and Masaquel are employees of Genentech, and they have stock options in F. Hoffmann-La Roche. Veenstra reports fees from Genentech, during the conduct of this study and outside of the submitted work. This work was presented, in part, at the AACR Virtual Meeting Advances in Malignant Lymphoma meeting (virtual; August 17-19, 2020) and the SOHO annual meeting (virtual; September 9-12, 2020).

Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma.

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000-2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan-Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma.

Aim: To evaluate the cost-effectiveness of polatuzumab vedotin (pola) + bendamustine + rituximab (BR) in relapsed/refractory diffuse large B-cell lymphoma based on the GO29365 trial from a US payer's perspective. Materials & methods: A partitioned survival model used progression-free survival and overall survival data from the GO29365 trial. The base case analysis assumed overall survival was informed by progression-free survival; a mixture cure model estimated proportion of long-term survivors. Results: In the base case, pola + BR was cost-effective versus BR at US$35,864 per quality-adjusted life year gained. Probabilistic and one-way sensitivity analyses showed that the findings were robust. Conclusion: Pola + BR is cost-effective versus BR for the treatment of transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma in the US.

Maintenance rituximab in Veterans with follicular lymphoma.

Real-world practice patterns and clinical outcomes in patients with follicular lymphoma (FL), including the adoption of maintenance rituximab (MR) therapy in the United States (US), have been reported in few studies since the release of the National LymphoCare Study almost a decade ago. We analyzed data from the largest integrated healthcare system in the United States, the Veterans Health Administration (VHA), to identify rates of adoption and effectiveness of MR in FL patients after first-line (1L) treatment. We identified previously untreated patients with FL in the VHA between 2006 and 2014 who achieved at least stable disease after chemoimmunotherapy or immunotherapy. Among these patients, those who initiated MR within 238 days of 1L composed the MR group, whereas those who did not were classified as the non-MR group. We examined the effect of MR on progression-free survival (PFS) and overall survival (OS). A total of 676 patients met our inclusion criteria, of whom 300 received MR. MR was associated with significant PFS (hazard ratio [HR]=0.55, P < .001) and OS (HR = 0.53, P = .005) compared to the non-MR group, after adjusting by age, sex, ethnicity, geographic region, diagnosis period, stage, grade at diagnosis, hemoglobin, lactate dehydrogenase (LDH), Charlson comorbidity index (CCI), 1L treatment regimen, and response to 1L treatment. These results suggest that in FL patients who do not experience disease progression after 1L treatment in real-world settings, MR is associated with a significant improvement in both PFS and OS. Maintenance therapy should be considered in FL patients who successfully complete and respond to 1L therapy.

Obinutuzumab plus chemotherapy followed by obinutuzumab monotherapy is cost-effective vs. rituximab plus chemotherapy followed by rituximab monotherapy for previously untreated follicular lymphoma patients in the United States.

The GALLIUM trial compared obinutuzumab (GA101, G)-based chemotherapy followed by G monotherapy (G + chemo) for up to two years to rituximab (R)-based chemotherapy followed by R monotherapy (R + chemo) for up to two years in previously untreated follicular lymphoma (FL) patients. We estimated the cost-effectiveness of G + chemo versus R + chemo utilizing GALLIUM trial data and published literature. G + chemo had increased drug costs (undiscounted: $135,200 versus $127,700 for R + chemo), representing a relative increase of 5.9%. However, this was offset by a $6,400 lower cost for disease progression. G + chemo led to increased quality-adjusted life years (QALYs) relative to R + chemo of 0.81 (95% credible range, [CR]: 0.22-1.37), and the overall discounted incremental cost was $1,900 (95% CR: -$7,400 to $8,900). The incremental cost-effectiveness ratio was ∼$2,300 per QALY gained, and the results were highly robust to sensitivity analyses. Treatment with G + chemo compared to R + chemo is cost-effective in previously untreated FL patients in the US.

Cost-effectiveness of obinutuzumab plus bendamustine followed by obinutuzumab monotherapy for the treatment of follicular lymphoma patients who relapse after or are refractory to a rituximab-containing regimen in the US.

AIMS: Obinutuzumab (GA101, G) was approved in February 2016 by the US Food and Drug Administration to treat follicular lymphoma (FL) patients who relapsed after, or are refractory to (R/R), a rituximab-containing regimen (R/R-rituximab). In the GADOLIN trial, R/R-rituximab patients who received G plus bendamustine (B) followed by G-monotherapy (G + B) for up to 2 years had significantly improved progression-free survival and overall survival compared to patients receiving B-monotherapy. This study estimated the cost-effectiveness of G + B vs B-monotherapy for R/R-rituximab FL patients from a US payer perspective. MATERIALS AND METHODS: Patient outcomes were simulated using a 3-state area under the curve model including progression-free survival, progressive disease, and death. This study used R/R-rituximab data from the National LymphoCare Study to extrapolate the GADOLIN trial's refractory FL progression-free and overall survival data to a R/R-rituximab FL population. Drug utilization and adverse events were based on trial data, and costs were based on Medicare reimbursements and drug wholesale acquisition costs in 2016. Utility estimates were derived from published literature. Post-progression treatment costs were based on observed post-progression therapies in GADOLIN. Sensitivity analyses were conducted to assess model uncertainty. RESULTS: G + B resulted in an increase in quality-adjusted life years relative to B-monotherapy of 1.24 (95% CR = 0.61-1.87); the incremental total cost was $58,100 (95% CR = $54,500-$61,500). The incremental cost-effectiveness ratio was $47,000 per QALY gained, and, based on probabilistic simulations, there was a 98% probability that G + B was cost-effective at the $100,000 per QALY threshold. LIMITATIONS AND CONCLUSIONS: This US-based analysis suggests that treatment with G + B compared to B-monotherapy is likely cost-effective in R/R-rituximab FL patients. Modeling a R/R-rituximab population based on a synthesis of GADOLIN and the National LymphoCare Study data introduces uncertainty in the analysis. However, the findings were robust to sensitivity analyses.

Does site-of-care for oncology infusion therapy influence treatment patterns, cost, and quality in the United States?

BACKGROUND: The increase in hospital acquisition of community oncology clinics in the US has led to a shift in the site-of-care (SOC) for infusion therapy from the physician office (PO) to the hospital outpatient (HO) setting. OBJECTIVE: To investigate differences by SOC in treatment patterns, quality, and cost among patients with cancer undergoing first-line infusion therapy. RESEARCH DESIGN AND METHODS: This retrospective analysis identified adult patients from Humana medical claims who initiated infusion therapy from 2008-2012 for five common cancer types in which infusion therapy is likely, including early stage breast cancer; metastatic breast, lung, and colorectal cancers; and non-Hodgkin's lymphoma or chronic lymphocytic leukemia. Differences by SOC in first-line treatment patterns and quality of care at end-of-life, defined as infusions or hospitalizations 30 days prior to death, were evaluated using Wilcoxon-Rank Sum and Chi-square tests where appropriate. Differences in cost by SOC were evaluated using risk-adjusted generalized linear models. MAIN OUTCOME MEASURES: Treatment patterns, quality of care at end of life, healthcare costs. RESULTS: There were differences in duration of therapy and number of infusions for some therapy regimens by SOC, in which patients in the HO had shorter duration of therapy and fewer infusions. There were no differences in quality of care at end-of-life by SOC. Total healthcare costs were 15% higher among patients in HO ($55,965) compared with PO ($48,439), p < .0001. LIMITATIONS: Analyses was restricted to a claims-based population of cancer patients within a health plan. CONCLUSION: This study, in an older, predominantly Medicare Advantage oncology cohort, found differences by SOC in treatment patterns and cost, but not quality. Where differences were found, patients receiving care in the HO had shorter duration of therapy and fewer infusions for specific treatment regimens, but higher healthcare costs than those treated in a PO.

Tools for Communication: Novel infrastructure to address patient-perceived gaps in oncology care
.

BACKGROUND: Healthcare providers (HCPs) and patient communication are integral to high-quality oncology care. The patient and HCP perspectives are needed to identify gaps in care and develop communication tools.
. OBJECTIVES: This study aimed to understand patient- and HCP-perceived elements of and gaps in high-quality care to develop novel communication tools to improve care. 
. METHODS: Qualitative interviews were conducted among 16 patients with cancer and 10 HCPs in the United States. Trained interviewers elicited patients' and HCPs' concerns, views, and perceived needs for communication tools. A thematic analysis was used to identify four quality of care domains, depicted in a conceptual model, and two draft communication tools were developed to address identified gaps.
. FINDINGS: No patients reported previously using a communication tool, and gaps in communication regarding treatment aims and education were evident. Two tools were developed to assess patients' life and treatment goals and the importance of ongoing education.

Patients' priorities in selecting chronic lymphocytic leukemia treatments.

Currently, in the United States, 130 000 people live with chronic lymphocytic leukemia (CLL), and almost 20 000 new cases of CLL are diagnosed each year. Little is known about the value patients place upon the attributes of available CLL treatments, which vary in efficacy, side effects, and mode of administration. We used a discrete-choice experiment (DCE) to investigate patients' preferences for treatment attributes and the impact of out-of-pocket cost on patients' choices. DCE surveys pose a series of choices between hypothetical treatment options, each defined by a set of attributes, and the responses provide quantitative estimates of the average relative preferences for treatment attribute. Each hypothetical treatment in this survey was defined by 5 attributes with predefined levels for efficacy, adverse events, and mode administration. A patient advocacy organization recruited 384 patients with a self-reported physician diagnosis of CLL to complete the online survey. Respondents placed the highest relative importance on longer progression-free survival (PFS). However, the risk of adverse events also was important, as significant additional PFS was needed to offset patients' acceptance of worsening adverse events. A supplemental question with 2 treatments and varying costs was included to assess the impact of cost on choice. When costs were included, a large proportion of patients changed their choices between the 2 treatments. Given the available treatments and the high cost of some treatments, physicians may want to explore their patients' preferences for different treatment features, including benefit-risk tradeoffs and out-of-pocket cost, when selecting the best treatment strategies for patients.

Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system.

BACKGROUND: Breast cancer is treated with many different modalities, including chemotherapy that can be given as a single agent or in combination. Patients often experience adverse events from chemotherapy during the cycles of treatment which can lead to economic burden. OBJECTIVE: The objective of this study was to evaluate costs related to chemotherapy-related adverse events in patients with metastatic breast cancer (mBC) in an integrated health care delivery system. METHODS: Patients with mBC newly initiated on chemotherapy were identified and the first infusion was defined as the index date. Patients were ≥18 years old at time of index date, had at least 6 months of health plan membership and drug eligibility prior to their index date. The chemotherapy adverse events were identified after the index date and during first line of chemotherapy. Episodes of care (EOC) were created using healthcare visits. Chart review was conducted to establish whether the adverse events were related to chemotherapy. Costs were calculated for each visit, including medications related to the adverse events, and aggregated to calculate the total EOC cost. RESULTS: A total of 1,682 patients with mBC were identified after applying study criteria; 54% of these patients had one or more adverse events related to chemotherapy. After applying the EOC method, there were a total of 5,475 episodes (4,185 single episodes [76.4%] and 1,290 multiple episodes [23.6%]) related to chemotherapy-related adverse events. Within single episodes, hematological (1,387 EOC, 33.1%), musculoskeletal/pain related (1,070 EOC, 25.6%), and gastrointestinal (775 EOC, 18.5%) were the most frequent adverse events. Patients with adverse events related to single EOC with anemia and neutropenia had the highest total outpatient costs with 901 EOC ($81,991) and 187 EOC ($17,017); these patients also had highest total inpatient costs with 46 EOC ($542,798) and 16 EOC ($136,768). However, within multiple episodes, hematological (420 EOC, 32.6%), followed by infections/pyrexia (335 EOC, 25.9%) and gastrointestinal (278 EOC, 22.6%) were the most frequent adverse events. CONCLUSION: The economic burden related to chemotherapy adverse events in patients with mBC is substantial.

The economic burden of end-of-life care in metastatic breast cancer.

OBJECTIVE: To assess end-of-life (EOL) total healthcare costs and resource utilization during the last 6 months of claims follow-up among patients with metastatic breast cancer (MBC) who received systemic anti-neoplastic therapy. METHODS: Newly diagnosed females with MBC initiating treatment January 1, 2003-June 30, 2011 were identified in a large commercial claims database. Two cohorts were defined based on a proxy measure for EOL 1 month prior to the end of last recorded follow-up within the study period: patients who were assumed dead at end of claims follow-up (EOL cohort) and patients who were alive (no-end-of-life [NEOL] cohort). Proxy measures for EOL were obtained from published literature and clinical expert opinion. Cost and resource utilization were evaluated for the 6 months prior to end of claims follow-up. Baseline variables, resource utilization, and costs were compared between cohorts with univariate statistical tests. Adjusted relative risks were calculated for resource utilization measures. A covariate-adjusted generalized linear model evaluated 6-month total healthcare costs. RESULTS: Of the 3,878 females included, 18.5% (n = 718) met the criteria for EOL. Mean observational time (MBC onset to end of claims follow-up) was shorter for the EOL cohort (EOL, 32 months vs NEOL, 35 months; p < 0.001). In adjusted analyses, the EOL cohort had 4.15 times higher 6-month total healthcare costs (EOL, $72,112 vs NEOL, $17,137; p < 0.001). NEOL month-to-month mean total healthcare costs fluctuated between $2336-$3145, while EOL costs increased steadily from $8,956 in the sixth month prior to death to $19,326 in the last month of life. The adjusted relative risk of inpatient, hospice and emergency department utilization was >2 times higher in the EOL cohort (p < 0.001). CONCLUSIONS: Potential EOL presented a greater economic burden in the 6 months prior to death. EOL month-to-month costs increased precipitously in the last 2 months of life and were driven by acute inpatient care.

Adverse event-related costs for systemic metastatic breast cancer treatment among female Medicaid beneficiaries.

OBJECTIVE: This retrospective study compared the real-world incidence and costs of systemic treatment-related adverse events (AEs) in patients with metastatic breast cancer in a Medicaid population. METHODS: Insurance claims data for adult women who received biologic or chemotherapy (± hormonal therapy) for metastatic breast cancer between 2006-2013 were extracted from the Truven Health MarketScan® Multi-State Medicaid database. Incidence of AEs (per 100 person years) and average monthly AE-related healthcare costs (per-patient-per-month) during each line of therapy (first or later lines) were estimated. The association between AEs and total all-cause healthcare costs was estimated using multivariable regression. RESULTS: A total of 729 metastatic breast cancer patients were analyzed. Hematological (202.3 per 100 person years) and constitutional AEs (289.6 per 100 person years) were the most common class of AEs reported. Unadjusted per-patient-per-month AE-related expenditure by class were highest for hematological AEs ($1524), followed by gastrointestinal ($839) and constitutional AEs ($795), with anemia ($942), nausea/vomiting ($699), and leukopenia/neutropenia ($550) having incurred the highest total AE-related costs. Adjusted total all-cause monthly costs increased with the number of AEs ($19,701 for >7 AEs, $16,264 for 4 - 6 AEs, and $13,731 for 1 - 3 AEs) compared to no AEs ($5908) (all p < 0.01). CONCLUSIONS: Among metastatic breast cancer patients treated with systemic therapy in a Medicaid population, AEs were associated with significant increases in costs, which increased with the number of AEs experienced. Therapies associated with a lower incidence of AEs may reduce cost burden and improve patient outcomes.

Survival in patients with non-metastatic breast cancer treated with adjuvant trastuzumab in clinical practice.

PURPOSE: The NSABP Trial B-31 and NCCTG Trial N9831 (B-31/N9831 trials, Romond et al. in N Engl J Med 353:1673-84, 2005. doi:10.1056/NEJMoa052122; Perez et al. in J Clin Oncol 32:3744-52, 2014. doi:10.1200/JCO.2014.55.5730) established the efficacy of adjuvant trastuzumab for patients with HER2-positive early stage breast cancer. We aimed to estimate the overall survival (OS) and relapse-free survival (RFS) of HER2-positive non-metastatic breast cancer patients treated with adjuvant trastuzumab in a clinical practice setting in the United States. METHODS: Adult women initiating adjuvant trastuzumab within 1 year of breast cancer surgery were identified in the health claims database of the US Department of Defense (01/2003-12/2012). OS and RFS unadjusted rates at 4 and 6 years after the first trastuzumab treatment following the breast cancer diagnosis were estimated from Kaplan-Meier analyses. RESULTS: The study sample included 3188 women followed for a median of 3.3 years after trastuzumab initiation and treated continuously with trastuzumab for a median of 12 months. The OS rates (95 % confidence intervals) at 4 and 6 years were 90.0 % (88.6-91.2) and 87.1 (85.3-88.6), respectively. The corresponding RFS rates were 75.8 % (74.0-77.5) and 72.7 (70.7-74.7), respectively. The OS and RFS rates at 6 years reported in the B-31/N9831 trials were 89.8 and 81.4 %, respectively. CONCLUSIONS: OS rates estimated in this study were in range with those estimated in the B-31/N9831 trials, while RFS rates were lower. However, patients in the B-31/N9831 trials were younger and possibly had fewer comorbidities than patients in the current study; these differences were not adjusted for in the crude OS and RFS analyses.

Delay in initiation of adjuvant trastuzumab therapy leads to decreased overall survival and relapse-free survival in patients with HER2-positive non-metastatic breast cancer.

Trastuzumab reduces the risk of relapse in women with HER2-positive non-metastatic breast cancer, but little information exists on the timing of trastuzumab initiation. The study investigated the impact of delaying the initiation of adjuvant trastuzumab therapy for >6 months after the breast cancer diagnosis on time to relapse, overall survival (OS), and relapse-free survival (RFS) among patients with non-metastatic breast cancer. Adult women with non-metastatic breast cancer who initiated trastuzumab adjuvant therapy without receiving any neoadjuvant therapy were selected from the US Department of Defense health claims database from 01/2003 to 12/2012. Two study cohorts were defined based on the time from breast cancer diagnosis to trastuzumab initiation: >6 months and ≤6 months. The impact of delaying trastuzumab initiation on time to relapse, OS, and RFS was estimated using Cox regression models adjusted for potential confounders. Of 2749 women in the study sample, 79.9 % initiated adjuvant trastuzumab within ≤6 months of diagnosis and 20.1 % initiated adjuvant trastuzumab >6 months after diagnosis. After adjusting for confounders, patients who initiated trastuzumab >6 months after the breast cancer diagnosis had a higher risk of relapse, death, or relapse/death than those who initiated trastuzumab within ≤6 months of diagnosis (hazard ratios [95 % CIs]: 1.51 [1.22-1.87], 1.54 [1.12-2.12], and 1.43 [1.16-1.75]; respectively). The results of this population-based study suggest that delays of >6 months in the initiation of trastuzumab among HER2-positive non-metastatic breast cancer patients are associated with a higher risk of relapse and shorter OS and RFS.