Racial and ethnic characteristics and outcomes of patients diagnosed with CLL/SLL in the United States.

Background This study was designed to compare outcomes among patients by race and ethnicity in the post-covalent Bruton tyrosine kinase inhibitor (cBTKi) treatment era. Methods A nationwide electronic health record (EHR)-derived de-identified database was utilized that included patients diagnosed with CLL from 2013-2022 who received systemic therapy for their disease. Use of cBTKi therapy, time to next treatment or death (TTNT-D), and overall survival (OS) were compared by race in unadjusted (Kaplan-Meier method) and adjusted analyses (Cox proportional hazards regression). Results This study included 4,572 White (71.8%) and 558 Black (8.8%) patients with CLL; 270 were Hispanic or Latino (4.2%). Patients who were Black were significantly younger, more were female, had later stage disease, were of lower socioeconomic status (SES), more likely to have unmutated immunoglobulin heavy chain gene (IGHV) and to havereceived cBTKi therapy than White patients (all p≤0.002). SES was also significantly different by ethnicity. TTNT-D and OS were not different by race in either unadjusted or adjusted analyses (all p>0.05). Conclusion In unadjusted and adjusted analyses, TTNT-D and OS were not different by race. These data did not identify racial healthcare disparities in the era following the introduction of cBTKi therapy despite differences in baseline characteristics.

Biomarker Testing, Targeted Therapy and Clinical Trial Participation by Race Among Patients With Lung Cancer: A Real-World Medicaid Database Study.

Introduction: Biomarker testing in oncology is fundamental for targeted therapy use and clinical trial participation. Factors contributing to previously identified racial disparities in biomarker testing remain unclear. This study investigated biomarker testing, clinical trial participation, and targeted therapy by race among patients with metastatic lung cancer with Medicaid coverage in the United States. Methods: The Merative MarketScan Medicaid claims database was used for this study to identify patients diagnosed with having metastatic lung cancer between 2017 and 2019 with at least 121 days of follow-up. Racial differences in biomarker testing, clinical trial enrollment, and targeted therapy use were analyzed using chi-square/t tests followed by logistic regression for confounding covariates. Results: A total of 3845 patients were eligible. A total of 970 (25.2%) patients included in this study were Black. Biomarker testing was observed among 57.0%, targeted therapy among 4.6%, and 2.6% of the study cohort had evidence of clinical trial participation. No significant disparities between Black and White races were identified. Younger age and metastatic disease at initial diagnosis were the strongest independent factors associated with increased biomarker testing. Biomarker testing was positively associated with targeted therapy use (OR = 1.69, p = 0.005). Conclusions: Patients with metastatic lung cancer with Medicaid coverage were found to have exceedingly low biomarker testing rates; only 57% had evidence of any biomarker testing. Although no consistent differences between Black and White races were identified, this study calls attention to care experienced by socioeconomically disadvantaged patients with metastatic lung cancer in the United States.

Mixed-methods research to support the use of new lymphoma-specific patient-reported symptom measures derived from the EORTC item library.

BACKGROUND: No specific measures exist to assess patient-reported symptoms experienced by individuals with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL). This study was conducted to elicit patient-reported CLL/SLL- and MCL-related symptoms and their impact on patients' lives. The study qualitatively and quantitatively evaluated sets of conceptually-selected EORTC Item Library items for assessing CLL/SLL- and MCL-related symptoms. METHODS: The qualitative component of the research included a literature review, clinician consultations, and patient interviews. Concepts important to patients were identified and coded; cognitive debriefing of the selected library items was completed with patients. CLL/SLL and MCL-related symptoms and impacts were organized in a structured conceptual model, which was mapped to item sets from the Item Library. The quantitative component comprised exploratory macro-level Rasch measurement theory (RMT) analysis conducted to provide supportive quantitative insight on the item sets. RESULTS: 41 patients (21-MCL; 20-CLL/SLL) and 5 clinicians participated in the qualitative study; 57 unique patients (30-MCL; 27-CLL/SLL) completed the EORTC items. The conceptual models generated from the qualitative work included symptoms and functional impacts of CLL/SLL and MCL. Symptom domains included swollen lymph nodes, B symptoms, abdominal issues, pain, fatigue, subjective cognitive impairment, anemia-related symptoms, bleeding, infection, and other issues (appetite loss, temperature fluctuation, rash, weight gain, sleep problems, cough). Impacts included physical function, role function, and other functions (psychological, social). Cognitive debriefing demonstrated that the separate item sets for CLL/SLL and MCL-related symptoms were well understood and aligned with patients' experiences. All selected items were included in the conceptual models. The exploratory RMT analysis showed that the item sets provided adequate coverage of the continuum of CLL/SLL- and MCL-related symptom severity. CONCLUSIONS: This study gathered qualitative and early quantitative evidence supporting use of the EORTC Item Library to assess CLL/SLL- and MCL-related symptoms and impacts. These items are promising candidates for measurement of patient-reported disease symptoms in these populations. A larger sample size will be essential to establish the psychometric properties necessary to support use in clinical trials. Patients who suffer from rare cancers of the blood, bone marrow, and lymph nodes can experience chronic and debilitating symptoms. At present, however, there are no dedicated instruments for assessing the patient's experience of symptoms of conditions like chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL), or for assessing their impact on patients' lives. This research project aimed to address that need. The researchers selected relevant and clinically meaningful symptoms from the EORTC Item Library that assess fatigue, B symptoms, and CLL/SLL- and MCL-specific symptoms. Using patients and clinician interviews as well as quantitative analyses, the research revealed no major concerns with using these item sets to assess symptoms of CLL/SLL and MCL. Interviews with patients demonstrated that the separate item sets for CLL/SLL and MCL-related symptoms were well understood and aligned with patients' experiences. All selected items were included in the conceptual models. Item sets identified in this study can potentially be used to assess patient-reported symptom endpoints in clinical trial settings in these disease areas.

Pirtobrutinib versus venetoclax in covalent Bruton tyrosine kinase inhibitor-pretreated chronic lymphocytic leukemia: a matching-adjusted indirect comparison.

Venetoclax is a standard treatment for patients with CLL following covalent BTK inhibitor (cBTKi) therapy, despite relatively limited prospective data in this setting. Pirtobrutinib is a highly selective, non-covalent (reversible) BTKi that was designed to overcome the pharmacologic limitations of cBTKi and re-establish BTK inhibition. An unanchored matching-adjusted indirect comparison (MAIC) was conducted to estimate the treatment effect of pirtobrutinib versus venetoclax monotherapy in patients with cBTKi pre-treated CLL. Data from patients with CLL who were venetoclax-naïve and pre-treated with cBTKi received pirtobrutinib (n=146) in the phase 1/2 BRUIN study were compared with the only identified trial of patients with CLL receiving venetoclax after a cBTKi (n=91), as administered as monotherapy until progression. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and treatment-emergent adverse events (TEAEs). Both unweighted and weighted analyses were conducted. PFS and OS of pirtobrutinib and venetoclax were comparable in both unweighted and weighted analyses (weighted hazard ratios for PFS: 1.01, 95% CI: 0.58-1.73, p=0.98 and OS: 0.64, 95% CI: 0.25-1.67, p=0.34). ORR was significantly higher for pirtobrutinib (80.2% vs 64.8%, p=0.01). Grade ≥3 TEAEs were lower in weighted analyses for pirtobrutinib vs venetoclax (all p.

Initial versus early switch to targeted therapy during first-line treatment among patients with biomarker-positive advanced or metastatic non-small cell lung cancer in the United States.

OBJECTIVES: This study compared outcomes between patients with biomarker-positive advanced/metastatic non-small cell lung cancer (a/mNSCLC) who initiated treatment with targeted therapy versus those who initiated chemotherapy-based treatment and switched to targeted therapy during the first ∼3 cycles (defined as the first 56 days) of first-line treatment. MATERIALS AND METHODS: This was an observational study of patients with a/mNSCLC who received targeted therapy from a nationwide electronic health record (EHR)-derived de-identified database. Outcomes were compared between those who initiated targeted therapy versus those who switched from chemotherapy to a targeted agent. Time-to-event outcomes were evaluated using Kaplan-Meier method; Cox proportional hazards models (adjusted for baseline covariates) were used to compare outcomes between groups. RESULTS: Of the 4,244 patients in this study, 3,107 (73.2%) initiated the first line with targeted therapy and 346 (8.2%) switched to targeted therapy. Patients who received initial targeted therapy were significantly more likely to be non-smokers, treated in an academic practice setting, and of slightly older age (all p < 0.05). Patients who received initial targeted therapy also had a significantly longer time to start of first-line treatment (35.8 vs 25.3 days, p < 0.001). No significant differences were observed for clinical outcomes between groups. CONCLUSION: In both unadjusted and adjusted analyses, there were no differences in the clinical outcomes observed among patients with a/mNSCLC in this study. This study found that initiating chemotherapy with an early switch to targeted therapy (within 56 days) of receiving biomarker positive results may be an acceptable strategy for a patient for whom immediate care is needed.

Biomarker Testing, Treatment, and Outcomes in Patients With Advanced/Metastatic Non-Small Cell Lung Cancer Using a Real-World Database.

BACKGROUND: Little is known about the impact of up-front biomarker testing on long-term outcomes in patients with advanced or metastatic non-small cell lung cancer (a/mNSCLC). This study compared overall survival (OS) by biomarker testing status and by receipt of guideline-concordant therapy in a large real-world cohort of patients with a/mNSCLC in the United States. PATIENTS AND METHODS: This retrospective study used an a/mNSCLC database derived from real-world electronic healthcare records. Patients diagnosed with nonsquamous a/mNSCLC who initiated first-line therapy on or after January 1, 2015, were included. We describe the testing of patients for actionable biomarkers and whether they subsequently received guideline-recommended first-line treatment. OS was defined as the number of months from the initiation of first-line therapy to the date of death or end of follow-up, and was described using Kaplan-Meier analysis. Multivariable Cox proportional hazard modeling was conducted to compare OS between groups adjusting for baseline covariates; adjusted hazard ratios (HRs) were reported. RESULTS: A total of 21,572 patients with a median age of 69 years (IQR, 61-76 years) and follow-up of 9.5 months (IQR, 3.5-21.5 months) were included. Among patients in the database, 88% had a record of receiving testing for at least 1 biomarker at any time, and 69% of these patients received testing before or at the start of first-line treatment. The adjusted hazard of death was 30% higher in patients who never (vs ever) received biomarker testing in the database (HR, 1.30; 95% CI, 1.24-1.37), and 12% higher in patients who did not receive (vs did receive) biomarker testing before or at the start of first-line treatment (HR, 1.12; 95% CI, 1.08-1.16). The adjusted hazard of death was 25% higher in patients who did not receive guideline-concordant first-line treatment (vs those who did) after having a biomarker-positive disease (HR, 1.25; 95% CI, 1.13-1.40). CONCLUSIONS: Findings suggest that receipt of first-line treatment that is concordant with biomarker testing results and treatment guidelines is associated with improved survival outcomes in patients with a/mNSCLC in the United States.

Real-World Biomarker Testing Patterns in Patients With Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) in a US Community-Based Oncology Practice Setting.

INTRODUCTION/BACKGROUND: This study was designed to describe real-world changes in biomarker testing among patients with non-squamous, metastatic non-small cell lung cancer (mNSCLC) in a community oncology setting from 2015 to 2020. PATIENTS AND METHODS: This retrospective study randomly selected 500 adult patients diagnosed with nonsquamous mNSCLC to undergo chart review and data extraction. Data were extracted and validated by 2 independent abstractors. Biomarker testing rates were described before and after national guideline updates and FDA approval of targeted agents. RESULTS: At least 1 biomarker test was received by 89.4% of patients with mNSCLC. Of all patients, 46.6%, 34.6%, and 8.2% received both single-gene and next generation sequencing (NGS)-based testing, single-gene testing only, and NGS-based testing only, respectively. However, there were changes in testing rates at the time of drug approvals for targeted agents. Biomarker testing increased for ALK (45.0% before to 78.3% after ALK-targeted drug approval), BRAF (from 20.0% to 67.8%), EGFR (from 20.0% to 78.2%), NTRK (from 34.6% to 55.7%), and ROS1 (increased from 29.6% before approval to 74.2% after). Biomarker testing increased after changes were made to national guidelines for BRAF (from 18.8% before to 68.1% after inclusion in guidelines), NTRK (from 37.2% to 56.5%), and ROS1 (increased from 40.8% to 74.5% after guideline updates). Targeted therapy was received by 62.4% of patients with a positive biomarker. CONCLUSION: Increases in biomarker testing rates were observed relative to targeted agent approvals and national guideline updates. However, many patients with non-squamous mNSCLC did not receive full genotyping in accordance with national guidelines and represent an opportunity to identify reasons and solutions for barriers to care.

Clinical outcomes among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who received treatment with a covalent BTK and BCL2 inhibitor in the United States: a real-world database study.

This retrospective study using the nationwide de-identified Flatiron Health electronic health record-derived database was designed to evaluate clinical outcomes among patients with chronic lymphocytic leukemia (CLL) who previously received both a covalent Bruton's tyrosine kinase inhibitor (cBTKi) and B-cell lymphoma 2 inhibitor (BCL2i) in a real-world setting. Outcomes for the immediate next line of therapy following the latter of the cBTKi or BCL2i treatment included: real-world response rate of 34.4% (using methods most consistent with clinical trials); median duration of real-world response of 13.3 months; and median real-world progression-free survival of 9.2 months. Median overall survival was 25.5 months from the start of the immediate next line of therapy. There remains a need for more effective therapies after cBTKi and BCL2i therapy for patients with CLL.

Biomarker testing in patients diagnosed with advanced/metastatic medullary thyroid cancer in the USA.

Aim: To describe real-world testing patterns for RET in US patients with advanced/metastatic medullary thyroid cancer and determine consistency of real-world testing practices with national guidelines. Materials & methods: The authors performed a retrospective medical record analysis of patients with advanced/metastatic medullary thyroid cancer who initiated systemic therapy between 2013 and 2018. Seventy-five US-based oncologists collected the data using a customized electronic data collection form. Results: A total of 59.6% (121 of 203) of patients underwent testing for RET, and 37.2% (45 of 121) had a RET mutation, of which 55.6% were identified as RET mutation-positive before initial diagnosis. Overall, 90 (44.3%) patients were tested for biomarkers on or after initial diagnosis, with RET being the most tested (95.6%) biomarker. Conclusion: The authors' findings suggest an opportunity to improve testing rates in accordance with treatment guidelines.

Mutations in the RET gene are common in patients with medullary thyroid cancer (MTC). As RET mutations are involved in the development of MTC, several treatment guidelines recommend counseling patients and testing for mutations in the RET gene in all patients with MTC. However, limited data are available on RET testing patterns in the USA in this patient population. In this study, the authors determined testing patterns for RET in patients with advanced or metastatic MTC in the USA using real-world data and found that only 60% of patients were tested for RET (i.e., testing for presence of RET mutations was observed in less than two-thirds of all patients included in the study). These results demonstrate the need for improved testing for RET mutations in patients with MTC in alignment with the treatment guidelines in routine clinical practice in the USA.

Outcomes for Patients With Chronic Lymphocytic Leukemia (CLL) Previously Treated With Both a Covalent BTK and BCL2 Inhibitor in the United States: A Real-World Database Study.

PURPOSE: This study describes the treatment patterns and outcomes of patients with CLL/SLL in a de-identified real-world oncology electronic health records database. METHODS: Adult patients with CLL/SLL were eligible if they had received cBTKi therapy, both a cBTKi and a BCL2i, or all 4 drug classes (cBTKi, BCL2i, rituximab, and chemotherapy) at any time during the first 5 lines of therapy. Time-to-event outcomes were evaluated using Kaplan Meier method. No statistical comparisons were conducted; all analyses were descriptive and conducted using SAS Enterprise. RESULTS: A total of 9578 patients were eligible: 52.0% (n = 4983) received at least one cBTKi, 6.1% (n = 581) received both a cBTKi and BCL2i, and 2.3% (n = 218) received all four therapies (cBTKi, BCL2i, rituximab, and chemotherapy). Of those who discontinued these treatments, only 39.5% (n = 1 206/3 577), 59.7% (n = 228/382), and 55.0% (n = 82/149) received subsequent therapy (post-cBTKi, post-cBTKi/post-BCL2i, and post-all 4 therapies, respectively). Median time from treatment discontinuation of these therapies to the discontinuation of subsequent therapy or death was 9.5 months (all patients who discontinued the cBTKi) 5.6 months (those who discontinued both a cBTKi and BCL2i) and 3.9 months (patients who discontinued all four therapies). The median duration of the next treatment among those who received additional therapy was post-cBTKi treatment duration = 4.1 months; post-cBTKi/post-BCL2i treatment duration = 5.5 months; and median duration of the immediate next therapy after discontinuation of all 4 therapies = 5.1 months. CONCLUSIONS: The poor outcomes observed across cohorts in this study demonstrate the need for effective treatments that can improve outcomes in patients with CLL/SLL.

Costs of biomarker testing among patients with metastatic lung or thyroid cancer in the USA: a real-world commercial claims database study.

OBJECTIVE: This real-world retrospective database study quantified the costs of biomarker testing in a US population of patients with lung or thyroid cancers. MATERIALS AND METHODS: The commercial claims IBM Marketscan database, a de-identified real-world dataset, was used to identify patients diagnosed with lung or thyroid cancer between 1/2015 and 12/2019. Eligible patients were 18 years or older with two or more lung or thyroid diagnosis codes. Patients were excluded who had evidence of prior cancer diagnoses. Subgroup analyses evaluated eligible patients with metastatic disease. Descriptive statistics were used to evaluate commercial insurance plan payer and patient out-of-pocket costs for diagnostic testing overall as well as by test procedure code and payer type. Costs were adjusted to 2020 US dollars. RESULTS: A total of 23,633 patients with lung cancer were eligible, 13,320 of whom had metastatic disease. There were 36,867 patients with thyroid cancer, 2,241 of whom had metastatic disease. Biomarker codes were observed among 68.4/75.8% (lung/metastatic lung) and 18.2/42.3% (thyroid/metastatic thyroid). Few patients had codes for comprehensive biomarker tests (5.2/6.7% lung/metastatic lung, 0.3/2.2% thyroid/metastatic thyroid) Among those with biomarker tests, the median per-patient total payer lifetime costs of all biomarker testing were $394/$462 (lung/metastatic lung) and $148/$232 (thyroid/metastatic thyroid). Total lifetime biomarker costs for payers ranged from a median of $128 (consumer-driven health plans) to $477 (preferred provider organizations). Median lifetime patient out-of-pocket costs were $0.00 for both tumor types and all payer types except for consumer-driven health plans ($12 for thyroid and $10 for metastatic lung). CONCLUSIONS: While comprehensive testing adds to the cost of biomarker testing, these data suggest the relatively low lifetime cost of biomarker testing for both payers and patients. Costs for biomarker testing should not be a limitation to access among these populations with commercial insurance plans in the US.

This real-world retrospective database study found that there is a relatively low lifetime total cost of biomarker testing for the care of patients with lung or thyroid cancers. While comprehensive testing adds to the cost of biomarker testing, these data suggest the relatively low lifetime cost of biomarker testing for both payers and patients. Payer costs for biomarker testing do not appear to be limitation to access among populations with commercial insurance plans in this study.

Cardiac events among patients with sarcoma treated with doxorubicin by method of infusion: A real-world database study.

BACKGROUND: Administration of doxorubicin by continuous intravenous (CIV) infusion, versus bolus (BOL) administration, has been proposed to mitigate the risk of cardiac events. This study used real-world data to explore the association between mode of doxorubicin administration and duration of treatment, time-to-treatment failure (TTF), and cardiac events. METHODS: Occurrence of cardiac events after initiation of BOL versus CIV doxorubicin for sarcoma in the International Business Machines MarketScan claims database were compared. Duration of doxorubicin treatment, TTF, and time-to-first-cardiac event (TCE) were evaluated using Kaplan-Meier method and unadjusted and adjusted Cox regression models. RESULTS: A total of 196 patients were included in the BOL group and 399 in the CIV group. In unadjusted analyses, there were significant differences between BOL versus CIV for duration of doxorubicin treatment (median 1.4 vs. 2.1 months, p = .002), TTF (median 8.8 vs. 5.6 months, p = .002), and TCE (medians not reached, p = .03). Adjusting for baseline covariates, only TTF remained significant (hazard ratio: 0.71, 95% confidence interval 0.59-0.86, p = .0004), favoring BOL. CONCLUSIONS: While the risk of cardiac complications was higher with BOL in unadjusted analysis, the risk was no longer present in the adjusted analysis. While we cannot draw causal inferences due to the retrospective, nonrandomized study design, these data suggest that replacing BOL with prolonged CIV administration has not been effective as a strategy to mitigate cardiac events, given community standards of oncologic practice.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

BACKGROUND AND OBJECTIVES: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer. METHODS: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial. RESULTS: The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval [95% CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96-1.28). CONCLUSION: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.

Treatment heterogeneity and overall survival in patients with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma in the United States.

Background: Gastric or gastroesophageal junction (GEJ) adenocarcinoma is the most common form of gastric cancer diagnosed in the United States (US) each year. Diagnosis typically is in later stages of disease when it has advanced. Patients have been treated with a variety of regimens. Methods: The goal of this retrospective study was to understand if treatment patterns were becoming more homogeneous or remaining heterogeneous using the Herfindahl-Hirschman index (HHI) and if treatments were becoming more concordant to treatment guidelines published by the National Comprehensive Cancer Network (NCCN). HHI scores were calculated for each site by 2-year increments. Trend analyses were conducted for HHI scores over time using a linear regression model. Concordance to Category 1 and any category NCCN guidelines was determined based on the date treatment was initiated with the version of the NCCN guidelines at that time. Time trend analyses were conducted using linear regression models. This study utilized data from the Flatiron Advanced Gastric/Esophageal cohort. This study also examined overall survival (OS) rates estimated by the Kaplan-Meier method by line of therapy. Results: There were no statistically significant differences in HHI scores in the first-line setting over time, suggesting heterogeneity has not improved. Concordance to NCCN treatment guidelines for any category significantly increased over time, however Category 1 regimen concordance remained low in the first-line setting. Concordance over time improved in second-line treatment. Median OS from the start of first-line therapy was 13.57 months. There was no relationship between OS time from initiation of first-line therapy and HHI score, concordance with NCCN guidelines, or concordance with NCCN Category 1 guidelines in the first-line setting. Conclusions: Treatment heterogeneity persists in gastric cancer care, though there is a significant association between heterogeneity and concordance with both Category 1 and any category in the NCCN treatment guidelines, and that concordance has increased over time.

Biomarker Testing for Patients With Advanced/Metastatic Nonsquamous NSCLC in the United States of America, 2015 to 2021.

Introduction: NSCLC is a solid tumor with a growing number of actionable biomarkers that may inform treatment. Current guidelines recommend a broad, panel-based approach be taken to identify actionable markers. This retrospective study used a deidentified electronic health records database in the United States to evaluate utilization of various testing modalities. Methods: Data from all adult patients diagnosed with having advanced/metastatic nonsquamous NSCLC between January 2015 and March 2021 were eligible if there was evidence of systemic therapy within 90 days of diagnosis. Results: Records from a total of 17,513 patients (91.6% from community-based practices) were eligible with 83,064 genomic biomarker tests recorded from 2015 to 2021. The proportion of patients who received biomarker testing by next-generation sequencing (NGS)-based methods ranged from 28.3% in 2015 to 68.1% in 2020. The proportion of biomarker testing methods with inconclusive or unsuccessful results ranged from 3.4% for NGS to 9.7% for fluorescence in situ hybridization. The median time to receive results ranged from 4.0 days for polymerase chain reaction-based tests to 10.0 days for immunohistochemistry- and NGS-based tests. Median time to receive results was 8 days for academic and 9 days for community practices. Conclusions: These real-world data suggest increased adoption of NGS-based testing, yet nearly one-third of all patients with advanced/metastatic nonsquamous NSCLC still did not receive broad-based genomic testing by 2020.

Diagnostic Value and Cost-Effectiveness of Next-Generation Sequencing-Based Testing for Treatment of Patients with Advanced/Metastatic Non-Squamous Non-Small-Cell Lung Cancer in the United States.

The study evaluated the diagnostic value and cost-effectiveness of next-generation sequencing (NGS)-based testing versus various combinations of single-gene tests (SGTs) for selection of first-line treatment for patients with advanced/metastatic non-squamous non-small-cell lung cancer in the United States. A dynamic decision analysis model was developed comparing NGS versus SGT from a payer perspective. Inputs were obtained from published sources and included diagnostic performance, biomarker-positive disease rates, biomarker-directed recommendations for treatment, and survival outcomes. Costs were reported in 2020 US dollars. In the base case, NGS improved the detection of actionable biomarkers by 74.4%, increased the proportion of patients receiving biomarker-driven therapy by 11.9%, and decreased the proportion of patients with biomarker-positive disease receiving non-biomarker-driven first-line treatment by 40.5%. The incremental cost-effectiveness ratio per life-year gained of NGS testing versus SGT was $7224 (excluding post-diagnostic costs); the incremental cost-effectiveness ratio for NGS-directed therapy was $148,786 versus SGT-directed therapy. Sensitivity analyses confirmed the robustness of these findings; survival outcomes and targeted therapy costs had the greatest impact on results. Testing strategies with NGS are more comprehensive in the detection of actionable biomarkers and can improve the proportion of patients receiving biomarker-driven therapies. NGS testing may provide a cost-effective strategy for advanced/metastatic non-squamous non-small-cell lung cancer; however, the value of NGS-directed therapy varies by the willingness-to-pay threshold of the decision-maker.

Disparities in Biomarker Testing and Clinical Trial Enrollment Among Patients With Lung, Breast, or Colorectal Cancers in the United States.

PURPOSE: Comprehensive tumor biomarker testing is a fundamental step in the selection of highly effective molecularly driven therapies for a variety of solid tumors. The primary objective of this study was to examine racial differences in biomarker testing and clinical trial participation in the United States using a real-world database. METHODS: Patients in a real-world deidentified database diagnosed with advanced/metastatic non-small-cell lung cancer (NSCLC), metastatic colorectal cancer (CRC), or metastatic breast cancer were eligible. Biomarker testing and clinical trial participation was compared between Black and White racial groups using chi-squared test and stepwise logistic regression controlling for baseline covariates. RESULTS: A total of 23,488 patients met eligibility criteria. Next-generation sequencing (NGS) testing rates differed significantly between White versus Black race before first-line therapy (36.6% v 29.7%, P < .0001) and at any given time (54.7% v 43.8%, P < .0001) in the nonsquamous NSCLC cohort. Similar disparities in NGS testing rates at any time during the study were observed among patients with CRC (White 51.6%; Black 41.8%, P < .0001). No differences were observed in the breast cancer cohort. Patients of Black race were less likely to be treated in a clinical trial in the overall NSCLC cohort when compared with White counterparts (3.9% v 2.1%, P = .0002). A statistically significant relationship between biomarker/NGS testing and clinical trial enrollment was observed in all cohorts (P < .003) after adjusting for covariates. CONCLUSION: In a real-world database, significant disparities in NGS-based testing rates were observed between Black and White races in NSCLC and CRC. NGS and any biomarker testing were both associated with trial enrollment in all cohorts. There is a need for interventions to promote access to comprehensive testing for patients with advanced/metastatic tumors.

Quality of life of patients with soft tissue sarcoma treated with doxorubicin in the ANNOUNCE phase III clinical trial.

BACKGROUND: Patient-reported outcomes (PROs), including health-related quality of life, are recommended to be routinely collected in clinical trials, but data are limited from trials of sarcoma patients. In this analysis, pooled PRO data are reported from patients with advanced or metastatic soft tissue sarcoma (STS) enrolled to the ANNOUNCE phase III trial of doxorubicin-based therapy. METHODS: ANNOUNCE was a phase III trial that randomized 509 patients with STS to receive up to eight cycles of doxorubicin with olaratumab or placebo, followed by single-agent olaratumab or placebo. Dexrazoxane was allowed at any cycle of treatment. Participants completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30, which is scored 0-100), and Brief Pain Inventory Short Form Modified (mBPI-sf, scored from 0-10) at each treatment cycle. A descriptive analysis of the longitudinal data was conducted overall and by cumulative dose of doxorubicin received to inform the clinical care of patients with STS. Worsening on the QLQ-C30 was defined as a change of 10 points or more at any post-baseline assessment. Worsening on the mPBI-sf was defined as an increase of ≥2 points from baseline. RESULTS: The majority of participants completed the baseline and at least one subsequent PRO assessment within the trial (n = 460, 90.4% EORTC QLQ-C30; n = 454, 89.2%, mBPI-sf). Patients with STS enrolled to the ANNOUNCE trial had clinically meaningful problems with physical function and pain before initiating doxorubicin. Overall, those with fewer symptoms or better function at baseline received higher cumulative doxorubicin dose throughout the study. At baseline, mean QLQ-C30 fatigue was 29.9 with a median time to first worsening of 0.9 months, and mean nausea/vomiting was 6.5 with 1.4 months until worsening; mean physical function was 78.3 with median time to worsening of 2.1 months and mean health status was 66.8 with median time to first worsening of 1.6 months. Median time to worsening of pain was 7.9 months. CONCLUSION: Patients with advanced or metastatic sarcoma reported a relatively rapid decline in PROs during doxorubicin-based treatment, with patients with poorer symptoms at baseline (specifically fatigue), subsequently receiving less doxorubicin therapy. The availability of detailed summary data from the patient perspective during doxorubicin-based treatment may inform future care of these patients and can provide a resource for the development of PRO endpoints in future trials.

Diagnostic characteristics, treatment patterns, and clinical outcomes for patients with advanced/metastatic medullary thyroid cancer.

BACKGROUND: Medullary thyroid cancer (MTC) accounts for approximately 1.6% of new cases of thyroid cancer. The objective of this study was to describe patient characteristics, biomarker testing, treatment patterns, and clinical outcomes among patients with advanced/metastatic MTC in a real-world setting in the United States and to identify potential gaps in the care of these patients. METHODS: Selected oncologists retrospectively reviewed medical records of patients aged ≥ 12 years diagnosed with advanced MTC. Patients must have initiated ≥ 1 line of systemic treatment for advanced/metastatic MTC between January 2013-December 2018 to be eligible. Patient characteristics, biomarker testing, and treatment patterns were summarized descriptively; progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: The 203 patients included in this study had a mean (SD) age of 52.2 (10.4) years; mean (SD) duration of follow-up from start of first-line treatment was 24.5 (16.0) months. Most patients (82.8%) were initially diagnosed with stage IVA, IVB, or IVC disease. Among all patients, 121 (59.6%) had testing for RET mutations, of whom 37.2% had RET-mutant MTC. The RET-mutation type was reported for 28 patients; the most common mutations reported were M918T (64.3%) and C634R (32.1%). Of the 203 patients, 75.9% received only one line of systemic treatment for advanced disease, and 36% were still undergoing first-line therapy at the time of data extraction. Cabozantinib (30.0%), vandetanib (30.0%), sorafenib (17.2%), and lenvatinib (4.9%) were the most common first-line treatments. Among 49 patients who received second-line treatment, most received cabozantinib (22.4%), vandetanib (20.4%), lenvatinib (12.2%), or sunitinib (12.2%). Median PFS (95% confidence interval [CI]) from start of first- and second-line treatments was 26.6 months (20.8-60.8) and 15.3 months (6.6-not estimable [NE]), respectively. Median OS from initiation of first- and second-line treatment was 63.8 months (46.3-NE) and 22.4 months (12.4-NE), respectively. CONCLUSIONS: For the treatment of advanced/metastatic MTC, no specific preference of sequencing systemic agents was observed in the first- and second-line settings. Considering the recent approval of selective RET inhibitors for patients with RET-mutant MTC, future research should investigate how treatment patterns evolve for these patients.