Effectiveness of standard treatments in non-small-cell lung cancer with METexon14 skipping mutation: a real-world study.

Aim: To assess real-world clinical outcomes with standard therapies for advanced non-small-cell lung cancer (aNSCLC) with METexon14 skipping mutation (METex14). Methods: In an oncologists-led retrospective review of medical records, data were abstracted and analyzed for patients initiating first-line (1L) systemic therapy after 1 January 2017. Results: In total 287 aNSCLC patients with METex14, the real-world best overall response rate was 73.4% for capmatinib (n = 146), 68.8% for immunotherapy (IO) monotherapy (n = 48), 52.0% for chemotherapy (CT, n = 30), and 54.8% for IO + CT (n = 63). As compared with capmatinib, patients receiving IO (hazard ratio [HR]: 1.57; 95% CI: 0.77-3.20; p = 0.220), CT (HR: 2.41; 95% CI: 1.19-4.85; p = 0.014) and IO + CT (HR: 2.33; 95% CI: 1.35-4.04; p = 0.003) had higher rates of progression. Further, patients receiving CT (HR: 4.43; 95% CI: 1.54-12.75; p = 0.006) and IO + CT (HR: 3.53, 95% CI: 1.41-8.85; p = 0.007) had higher rates of mortality than patients receiving capmatinib. Conclusion: The study showed better clinical outcomes with capmatinib than other standard therapies in 1L setting for aNSCLC harboring METex14.

Real-world study that investigated the outcomes of different therapies used to treat non-small-cell lung cancer patients with mesenchymal-epithelial transition exon 14 skipping mutationWhat is this article about? A real-world study that investigated clinical outcomes in patients with diagnosis of advanced non-small-cell lung cancer (aNSCLC) with mesenchymal-epithelial transition exon 14 (METex14) skipping­a rare form of genetic mutation­who received treatment with one of the commonly used therapies for this disease: immunotherapy, chemotherapy, immunotherapy + chemotherapy combination and capmatinib, which is a highly selective inhibitor of MET tyrosine kinase protein involved in the growth of cancer cells.What were the results? The study showed that, in general, patients treated with capmatinib as the frontline therapy more frequently achieved a clinical response in the form of complete tumor resolution or tumor shrinkage, had a lower risk of disease worsening and lived longer than patients who were treated with immunotherapy, chemotherapy or immunotherapy + chemotherapy combination.What do the results of the study mean? This study suggests that capmatinib is effective in treating patients with aNSCLC with METex14 skipping who have not been treated with another anticancer therapy previously. It provides evidence to support the use of capmatinib in the frontline setting and may inform clinical decision-making in routine practice.

Real-world treatment patterns and clinical outcomes in patients treated with eribulin after prior phosphoinositide 3-Kinase inhibitor treatment for metastatic breast cancer.

PURPOSE: In 2010, the US Food and Drug Administration approved eribulin for the treatment of metastatic breast cancer (MBC). Since then, the treatment landscape has evolved with many new therapy classes, a more recent one being the small molecule inhibitors of phosphoinositide 3 kinase (PI3K). We sought to characterize the treatment patterns and clinical outcomes of patients with MBC who received eribulin following prior treatment with a PI3K inhibitor. METHODS: A retrospective cohort study based on medical record review included MBC patients who initiated eribulin between March 2019 and September 2020 following prior treatment with a PI3K inhibitor was conducted. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated from the initiation of eribulin therapy using Kaplan-Meier analyses. RESULTS: 82 eligible patients were included. Patients' median age at eribulin initiation was 62 years; 86.5% had hormone receptor-positive, human epidermal growth factor receptor 2-negative tumors. Eribulin was most often administered in the second or third line (82.9%) in the metastatic setting. Best overall response on eribulin was reported as complete or partial response in 72% of the patients. The median rwPFS was 18.9 months (95% confidence interval [CI], 12.4-not estimable); median OS was not reached. The estimated rwPFS and OS rates at 12 months were 63.3% (95% CI, 50.5-73.7) and 82.6% (95% CI, 72.4-89.3), respectively. CONCLUSION: Our real-world study suggests that eribulin may be a potential treatment option for MBC patients who fail a prior PI3K inhibitor.

Real-World Treatment Patterns and Clinical Outcomes Among Patients With Advanced Renal Cell Carcinoma.

BACKGROUND: Nearly 30% of new renal cell carcinoma (RCC) cases are diagnosed at an advanced or metastatic stage. Recent approvals of immunotherapies (IO) have significantly impacted patient care, but real-world outcomes of these treatments have not been widely evaluated. METHODS: Eligible physicians abstracted demographic and clinical data from patient medical records for patients with advanced clear and non-clear cell RCC (aRCC) who initiated treatment between January 1, 2018, and December 31, 2020. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. A multivariate Cox regression model was developed to assess the impact of treatment category on clinical outcomes while controlling for International Metastatic RCC Database Consortium (IMDC) risk category, histology, and other patient characteristics. RESULTS: A total of 498 patients were included (201 from US, 62 from Canada, 58 from UK, 59 from France, 58 from Germany, 60 from Spain). Of these, 250 received tyrosine kinase inhibitor (TKI) monotherapy, 197 received immunotherapy (IO) combination (119 IO+TKI, 78 IO+IO), and 32 received IO monotherapy as first-line treatment for aRCC; 19 patients received various other regimens. 16% of patients had a favorable IMDC risk score. Based on results of multivariable Cox regression, PFS (hazard ratio [HR] [95% confidence interval (CI)]: 0.50 [0.36-0.72]) (P < .001) and time to next treatment (TTNT) were significantly longer (HR [95% CI]: 0.54 [0.39-0.73]) (P < .001) for patients treated with IO combination versus TKI monotherapy. IO combination had a numerically reduced, but statistically insignificant, risk of death versus TKI monotherapy (HR: 0.66; P = .114). IO+TKI combination was associated with significantly longer PFS and reduced risk of progression (HR: 0.52; P = .04) versus IO+IO combination; similar results were observed for TTNT (HR: 0.57; P = .03). CONCLUSION: Our evaluation of real-world treatment outcomes in aRCC revealed that IO + TKI combination is associated with improved PFS and prolonged TTNT compared with TKI monotherapy and IO+IO combination.

Early Real-World Treatment Patterns and Clinical Outcomes in Patients with Metastatic Breast Cancer Treated with Eribulin After Prior Immuno-Oncology or Antibody-Drug Conjugate Therapy.

Introduction: Eribulin was approved by the FDA in 2010 for the treatment of metastatic breast cancer (MBC) in the United States (US). More recently, several immuno-oncology (IO) and antibody-drug conjugate (ADC) regimens have been approved for MBC. We assessed the treatment patterns and clinical outcomes in MBC patients treated with eribulin following treatment with an IO or ADC in US clinical practice. Materials and Methods: In a retrospective patient medical chart review study, patients with MBC, aged ≥18 years, who initiated eribulin therapy between March 1, 2019, and September 30, 2020, treated with either prior IO or ADC in the metastatic setting were included. Patient demographics, treatment characteristics, and clinical outcomes were analyzed descriptively. Real-world progression-free survival (rwPFS) and overall survival (OS) were estimated using Kaplan-Meier analyses. Results: In the study population (N=143), median age at eribulin initiation was 62 years; 64% were Caucasian, and 67% had triple-negative MBC (TNBC). Eribulin therapy was used in the second to fifth line of therapy in the metastatic setting; median treatment duration was 7.2 months. The overall response rate for eribulin was 59.4%. Median rwPFS and OS from eribulin initiation were 21.4 months (95% CI, 12.9-not estimable [NE]) and 24.2 months (95% CI, 17.5-NE), respectively. In patients with TNBC, median rwPFS and OS from eribulin initiation were 12.0 months (95% CI, 8.8-NE) and 18.3 months (95% CI, 14.9-NE), respectively. Conclusion: These real-world data provide evidence for the clinical effectiveness outcomes of eribulin treatment among MBC patients previously treated with an IO or ADC.

Improved Survival Outcomes in Patients With MET-Dysregulated Advanced NSCLC Treated With MET Inhibitors: Results of a Multinational Retrospective Chart Review.

BACKGROUND: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms. RESULTS: Overall, 211 patient charts were included in this analysis; 157 patients had MET exon 14 skipping mutations (METex14; with or without concomitant MET amplification) and 54 had MET amplification only. All patients were tested for METex14, whereas MET amplification was evaluated in 168 patients. No overlap was reported between MET dysregulation and ALK, ROS1 or RET rearrangements, or HER2 exon 20 insertions. Overall, 56 of 211 patients (26.5%) received MET inhibitor (METi) therapy in any treatment-line setting (31.2% in the METex14 cohort; 13% in the MET-amplified only cohort). In the METex14 cohort, median OS in patients receiving METi was 25.4 months versus 10.7 months in patients who did not (HR [95% CI]: 0.532 [0.340-0.832]; P = .0055). In the MET-amplified only cohort, median OS was 20.6 months in patients treated with METi compared with 7.6 months in those without METi (HR [95% CI]: 0.388 [0.152-0.991]; P = .0479). CONCLUSIONS: MET alterations in NSCLC typically occur in the absence of other oncogenic driver mutations and are associated with poor survival outcomes. Notably, METi therapies are associated with improved survival outcomes in patients with MET-dysregulated NSCLC.

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib.

Aim: To assess real-world clinical outcomes in patients with non-small-cell lung cancer with MET exon 14 skipping mutation and brain metastases (BM) who received capmatinib, a recently approved MET inhibitor, in routine US clinical practice. Materials & methods: Patient data were collected using a retrospective medical record review, led by participating oncologists. Eligible patients initiated treatment with capmatinib in any line, after BM diagnosis, between May 2020 and June 2021. Data on real-world overall response rate (rwORR) and real-world progression-free survival (rwPFS) were descriptively analyzed. Results: 68 eligible patients were analyzed. In patients treated with first-line (1L) capmatinib (n = 55), the rwORR was 90.9% systemically and 87.3% intracranially; median systemic rwPFS was 14.1 months. Among radiation-naive patients on 1L capmatinib (n = 20), rwORR was 85.0%, both systemically and intracranially; median systemic rwPFS was 14.1 months. Conclusion: This study showed substantial systemic and intracranial effectiveness for capmatinib in real-world setting; findings were consistent for RT-naive patients.

Real-World Effectiveness of Lenvatinib in Hepatocellular Carcinoma Patients with Nonalcoholic Steatohepatitis.

Hepatocellular (HCC) is the most common type of primary liver cancer and the fourth most common cause of cancer-related deaths globally.1 Although most cases of HCC were historically attributed to underlying chronic viral hepatitis, nonalcoholic fatty liver disease is projected to become the most common risk factor for HCC with the rising prevalence of obesity and diabetes mellitus and increasing availability of effective treatments for hepatitis B and C infection.2 Although patients with viral and nonviral HCC seem to have similar overall prognosis,3 prior data have suggested possible differential efficacy of systemic therapies by liver disease etiology. For example, sorafenib was shown to have greater efficacy in patients with chronic hepatitis C infection than other etiologies.4 The aim of our descriptive study was to report the effectiveness of lenvatinib in a real-world cohort of patients with nonalcoholic steatohepatitis (NASH)-related HCC.

Real-world effectiveness of lenvatinib monotherapy in previously treated unresectable hepatocellular carcinoma in US clinical practice.

BACKGROUND: Lenvatinib monotherapy was approved in the United States for first-line treatment of patients with unresectable hepatocellular carcinoma (uHCC) in 2018. This study assessed real-world treatment patterns and outcomes of lenvatinib beyond first-line systemic treatment in the United States. METHODS: A retrospective study was conducted among US adults (≥18 years) with uHCC. Eligible patients initiated lenvatinib monotherapy as second- or later-line systemic therapy (2L-plus) from August 2018 to September 2019. Clinical outcomes included physician-reported best response, progression-free survival (PFS), and overall survival (OS). RESULTS: Of 164 patients who received lenvatinib in 2L-plus, most (n = 133; 81.1%) received lenvatinib in 2 L. There were 109 patients (66.4%) who initiated lenvatinib after immunotherapy. At lenvatinib initiation, only 31.1% of patients had Child-Pugh class A, while half (49.4%) had Child-Pugh class B. Most patients had Barcelona Clinic Liver Cancer stage B (23.8%) or C (38.4%) uHCC. Median duration of lenvatinib treatment was 6.9 months, with 42.7% of patients still on treatment at the end of follow-up. Physician-reported best response was complete and partial response for 8.5% and 44.5% of patients, respectively. PFS and OS rate estimates from lenvatinib initiation at 12 months were 51.7% and 57.8%, respectively. Among patients treated after immunotherapy, complete and partial responses were 10.1% and 43.1%, respectively, and PFS and OS estimates from lenvatinib initiation at 12 months were 52.8% and 60.0%, respectively. CONCLUSION: This retrospective study suggests clinical effectiveness of lenvatinib monotherapy in a real-world setting among previously treated patients with uHCC, including among those previously treated with immunotherapy.

Efficacy comparison of tisagenlecleucel vs usual care in patients with relapsed or refractory follicular lymphoma.

The ELARA trial indicates tisagenlecleucel (tisa-cel) is an effective anti-CD19 chimeric antigen receptor T-cell therapy for relapsed or refractory follicular lymphoma (r/r FL). As ELARA is a single-arm trial, this study compares tisa-cel outcomes from the ELARA trial with usual care from a real-world cohort. ELARA enrolled 98 patients as of 29 March 2021 (median follow-up: 15 months from enrollment). Usual care data were obtained from ReCORD-FL, a global retrospective study of patients with r/r FL, who met similar eligibility criteria to ELARA. With a data cutoff date of 31 December 2020, 187 patients with ≥2 preceding treatment lines were included in the ReCORD-FL (median follow-up: 57 months from third-line) study. An indirect treatment comparison was performed for 97 patients from the ELARA trial and 143 patients from the ReCORD-FL study with no missing data on baseline factors. The line of therapy for which outcomes were assessed was selected or matched between cohorts using propensity score modeling. After baseline factor adjustment via weighting by odds, complete response rate (CRR; 95% confidence interval) was 69.1% (59.8%-78.3%) for tisa-cel vs. 37.3% (26.4%-48.3%) for usual care; overall response rate was 85.6% (78.7%-92.5%) vs. 63.6% (52.5%-74.7%). Kaplan-Meier probability of being progression/event-free at 12 months was 70.5% (61.4%-79.7%) for tisa-cel vs. 51.9% (40.6%-63.3%) for usual care, with hazard ratio (HR)=0.60 (0.34-0.86); 12-month overall survival was 96.6% (92.9%-100%) vs. 71.7% (61.2%-82.2%), with HR=0.2 (0.02-0.38). In conclusion, tisa-cel was associated with a 1.9-fold higher complete response rate and a 1.4-fold higher rate of being progression or event free at 12 months vs usual care, as well as a death risk reduction of 80%. The findings provide additional evidence on the benefit of tisa-cel in patients with r/r FL after ≥2 treatment lines. This trial was registered at www.clinicaltrials.gov as NCT03568461.

A Retrospective Cohort Study of Treatment Outcomes of Adult Patients With Relapsed or Refractory Follicular Lymphoma (ReCORD-FL).

This study (ReCORD-FL) sought to construct a historical control cohort to augment single-arm trials in relapsed/refractory follicular lymphoma (r/r FL). A retrospective study in 10 centers across North America and Europe was conducted. Adults with grade 1-3A FL were required to be r/r after ≥2 therapy lines including an anti-CD20 and an alkylator. After first becoming r/r, patients were required to initiate ≥1 additional therapy line, which defined the study index date. Endpoints were observed from start of each therapy line (including index line) until death, last follow-up, or December 31, 2020. Endpoints were complete response (CR) rate, overall response rate (ORR), time to next treatment or death (TNT-D), event-free survival (EFS), and overall survival (OS). One hundred eighty-seven patients were identified. Most patients' (80.2%) index therapy occurred in third line (3L) (range, 3L-6L). Median follow-up from FL diagnosis was 9 years (range, 1-21 years). CR and ORR to the index therapy were 39.0% and 70.6%, respectively. Median (95% confidence interval) EFS from index was 14.6 (11.0-18.0) months; median OS from index was 10.6 years. Outcomes worsened across successive treatment lines and for patients who were double refractory (r/r to both an anti-CD20 monoclonal antibody and an alkylator) or POD24 (progressed ≤24 months after front-line anti-CD20) at index. Findings demonstrate the unmet need of FL patients with multiply relapsed, double refractory, or POD24 disease. Based on robustness of the historical data collected and comparability with a previous study (SCHOLAR-5), ReCORD-FL presents a valuable source of control data for comparative studies in r/r FL.

Real-world clinical outcomes of patients with myelofibrosis treated with ruxolitinib: a medical record review.

Aim: To assess real-world ruxolitinib treatment patterns and outcomes in patients diagnosed with primary or secondary myelofibrosis. Materials & methods: Patient medical records were reviewed in six countries. Results: Eligible patients (n = 469) had a mean age of 63.5 years, and most were male (66.5%) with primary myelofibrosis (78.5%). Median duration of ruxolitinib treatment was 13.1 months; 40% of patients initiated treatment at the recommended dose. The Kaplan-Meier estimate of median survival from ruxolitinib initiation was 44.4 months (95% CI, 38.8-50.2 months). Approximately one quarter (23%) of patients continued ruxolitinib after progression. Conclusion: These results suggest an unmet need for more effective treatments for patients with myelofibrosis who failed ruxolitinib.

European and US Real-World Treatment Patterns in Patients with Epidermal Growth Factor Receptor Mutation-Positive Non-Small Cell Lung Cancer: A Retrospective Medical Record Review.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the preferred first-line (1L) therapy for EGFR mutation-positive (EGFRm) advanced/metastatic non-small cell lung cancer (NSCLC). OBJECTIVE: Our objective was to describe real-world treatment patterns and T790M testing practices in patients with 1L disease progression (Europe/USA) following treatment with first- or second-generation EGFR-TKIs. METHODS: This was a retrospective, non-interventional medical record review of patients with EGFRm locally advanced/metastatic NSCLC from routine clinical practice (EGFR-TKI initiation: 1 January 2015 to 31 December 2017; follow-up: last available medical record). Endpoints were demographic/clinical characteristics, incidence of central nervous system (CNS) metastases/leptomeningeal disease, second-line (2L) treatment, T790M mutation testing, and osimertinib treatment prevalence. RESULTS: Among 469 patients, 73% (n = 341/469) progressed on 1L EGFR-TKI treatment. Of those who progressed, 74% (n = 252/341) were tested for T790M, with 50% (n = 126/252) testing positive; 75% (n = 94/126) of T790M-positive patients received osimertinib (mostly 2L). Of the patients with progression, 24% (n = 83/341) did not receive 2L treatment, and 88% (n = 73/83) of these patients died. At diagnosis of advanced disease, 9% of patients (n = 41) had CNS metastases; at EGFR-TKI initiation, 14% of patients (n = 68) had CNS metastases. Over the study period, 11% of patients (n = 42) developed CNS metastases not detected at NSCLC diagnosis. CONCLUSIONS: Rates of resistance mutation testing and subsequent utilization of recommended 2L therapies could be improved. As more targeted therapies are developed, it will be crucial to improve the molecular testing rates to ensure patients receive appropriate, effective, and timely treatment.

Real-world effectiveness of lenvatinib monotherapy among unresectable hepatocellular carcinoma patients in the USA.

Aim: This study evaluated the effectiveness of lenvatinib monotherapy for first-line treatment of unresectable hepatocellular carcinoma (uHCC) in a real-world setting. Materials & methods: This retrospective cohort study included patients who initiated lenvatinib monotherapy as first-line treatment for uHCC (n = 233). Clinical outcomes included provider-reported best response, progression-free survival (PFS) and overall survival (OS). PFS and OS were estimated using Kaplan-Meier methods. Results: Most patients (67.8%) were male. A total of 44.6% had Child-Pugh A and 39.1% had Child-Pugh B. Dose reductions were reported in 9%. Median PFS and OS were not reached. At 6 and 12 months, landmark PFS were 85.1 and 64.9%, respectively; landmark OS were 91.8 and 72.6%, respectively. Conclusion: These results affirm the clinical effectiveness of first-line lenvatinib monotherapy in uHCC.

Lay abstract Lenvatinib is a targeted therapy that prevents tumor growth. It was approved for the treatment of advanced liver cancer in 2018, but few studies have examined how it is used in everyday clinical practice, especially in the USA. In this study, we reviewed the medical records of 233 patients in the USA with unresectable hepatocellular carcinoma, who were treated with lenvatinib in first line to better understand its effectiveness and use in real-world care. We collected information on how long they were on treatment and time to tumor progression and/or death. Overall, our study found that in this demographically and clinically diverse sample, results affirm findings from prior studies that found lenvatinib is an effective treatment for patients with unresectable hepatocellular carcinoma.

Overall survival, adverse events, and economic burden in patients with chronic lymphocytic leukemia receiving systemic therapy: Real-world evidence from the medicare population.

BACKGROUND: Information on overall survival (OS) and adverse events (AEs) in patients with chronic lymphocytic leukemia (CLL) is mostly available from clinical trials. We therefore conducted a population-based retrospective cohort study to assess OS, incidence of AEs, and economic burden in real-world practice among Medicare patients treated for CLL. METHODS: Patients with CLL receiving ≥1 systemic therapy from 2013 to 2015 were selected from the Medicare claims database and followed from the start of first observed systemic therapy (index date) through December 2016 or death. OS for patients receiving each of the most commonly observed treatments was estimated by the Kaplan-Meier method. AEs were assessed among patients receiving these treatments across all observed lines of therapy. All-cause direct medical costs were assessed from the Medicare system perspective. RESULTS: Among 7,965 eligible patients across all observed therapy lines, ibrutinib monotherapy (Ibr; n = 2,708), chlorambucil monotherapy (Clb; n = 1,620), and bendamustine/rituximab (BR; n = 1,485) were the most common treatments. For first observed therapy, 24-month OS estimates for Ibr, Clb, and BR recipients were 69% (95% CI = 68%-71%), 68% (95% CI = 65%-71%), and 79% (95% CI = 77%-81%) respectively. The most frequently recorded AEs in patients receiving these treatments in any observed line of therapy were neutropenia, hypertension, anemia, and infection. For all patients, the mean monthly all-cause cost during the follow-up period was $8,974 (SD = $11,562); cost increased by the number of AEs, from $5,144 (SD = $5,409) among those with 1-2 AEs to $10,077 (SD = $12,542) among those with ≥6 AEs. CONCLUSION: Over two-thirds of patients survived at least 2 years after starting their first observed therapy for CLL. Our findings highlight considerable susceptibility to AEs and unmet medical need in Medicare patients with CLL treated in routine practice. Medicare incurred substantial economic burden following initiation of systemic therapy, and patients with greater numbers of AEs accounted disproportionately for the high overall cost of CLL management.

Real-world treatment patterns, adverse events and clinical outcomes in patients with chronic lymphocytic leukaemia treated with ibrutinib in the UK.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults in the UK. Ibrutinib, an oral Bruton tyrosine kinase inhibitor (BTKi) for CLL approved by the UK's National Institute for Health and Care Excellence in January 2017, represented a major shift in CLL management. Real-world data on ibrutinib use in routine clinical practice will inform patients' and physicians' decision-making. We conducted a retrospective medical chart review of UK patients with CLL who initiated ibrutinib between January 2017 and July 2018. Data for 259 patients were contributed by 34 haematology-oncology specialists, with a median follow-up duration of 16.7 months. Median age at ibrutinib initiation was 71 years. Ibrutinib first-line monotherapy was prescribed in 20.1% of patients. Ibrutinib was permanently discontinued in 15.4% of patients, mostly owing to progressive disease. Adverse events (AEs) were reported in 151 patients (58.3%). The most common were bruising (19.3% of patients), cytopenias (17.0%) and diarrhoea (11.6%). Ibrutinib dose reduction was observed in 14.3% of patients and was temporarily discontinued in 10.4% of patients, with the main reason for both being toxicity. These results expand the real-world evidence on ibrutinib therapy and demonstrate a high burden of AEs, highlighting the need for more tolerable BTKis.

Treatment patterns, adverse events, and direct and indirect economic burden in a privately insured population of patients with HR+/HER2- metastatic breast cancer in the United States.

BACKGROUND: Real-world evidence specific to HR+/HER2- metastatic breast cancer (MBC) prior to introduction of CDK4/6 inhibitors is limited. In an effort to provide context for the introduction of new treatments, we assessed treatment patterns, adverse events, productivity loss, and direct/indirect economic burden in a privately insured population of patients with HR+/HER2- MBC. RESEARCH DESIGN AND METHODS: Using a retrospective cohort design, patients aged 18-64 years, selected from MarketScan databases (2007-2014), were analyzed using descriptive and multivariable methods. RESULTS: Among 5,563 eligible patients, endocrine therapy was the most common first-line (1L) therapy; its utilization trended downward from 63% (1L) to 23% (4L), with a simultaneous increase in chemotherapy use, 25% (1L) to 50% (4L). Two hundred and seventy-eight unique treatment regimens were used in the 1L setting. The average per patient monthly all-cause costs were $14,424. The 12-month indirect costs for short-term disability were substantially higher in MBC patients ($10,397) than in matched noncancer patients ($394). CONCLUSION: The increasing use of chemotherapy as patients progressed to second and later lines and the substantial direct/indirect economic burden underscore an unmet need. The high number of 1L regimens highlights significant heterogeneity and a lack of consensus related to the management of HR+/HER2- MBC in routine practice.

POLARIS: a prospective, multicenter, noninterventional study assessing palbociclib in hormone receptor-positive advanced breast cancer.

This report describes the rationale, purpose and design of the POLARIS study. POLARIS is an ongoing noninterventional, prospective, multicenter study. Female and male patients in the USA and Canada diagnosed with hormone receptor-positive/HER2-negative metastatic breast cancer were enrolled in the study and treated with the cyclin-dependent kinase 4/6 inhibitor palbociclib when hormone receptor-positive/HER2-negative metastatic breast cancer was deemed to be indicated by their physician. The study will provide real-world data on palbociclib prescribing and treatment patterns in routine clinical practice, associated clinical outcomes, treatment sequencing in the advanced/metastatic setting, patient quality of life and geriatric-specific assessments. The tumor genomic landscape in relation to clinical outcomes will be explored. POLARIS will identify benefits and side effects of palbociclib across multiple lines of therapy and in discrete subsets of patients. Clinical Trial Registration: NCT03280303 (ClinicalTrials.gov).

Achievement of Target A1C <7.0% (<53 mmol/mol) by U.S. Type 2 Diabetes Patients Treated With Basal Insulin in Both Randomized Controlled Trials and Clinical Practice.

OBJECTIVE: Many patients with type 2 diabetes do not reach glycemic goals despite basal insulin treatment. This study assessed the achievement of a target A1C <7.0% (<53 mmol/mol) after initiation of basal insulin in two settings. METHODS: This was a retrospective analysis of pooled randomized controlled trial (RCT) data, from 11 24-week studies of patients initiating basal insulin performed between 2000 and 2005 and of outpatient electronic medical record (EMR) data from the General Electric Centricity database for insulin-naive patients initiating basal insulin between 2005 and 2012. Baseline characteristics stratified by target A1C and fasting plasma glucose (FPG) attainment were compared descriptively. RESULTS: In the RCT dataset, 49.0% of patients failed to achieve the target A1C at 6 months versus 72.4% and 72.9% at 6 and 12 months in the EMR dataset, respectively. Despite this, in the RCT dataset, 79.4% of patients achieved the target A1C and/or an FPG <130 mg/dL. In the EMR dataset, only 47.6% and 47.3% of patients achieved an A1C <7.0% and/or FPG <130 mg/dL at 6 and 12 months, respectively. Overall, patients with an A1C >7.0% had a longer diabetes duration and were more likely to be female, nonwhite, and self-funding or covered by Medicaid. Among patients with an A1C >7.0%, more RCT patients (58.0%) had an FPG <130 mg/dL than EMR patients at 6 months (27.8%) and 12 months (27.7%). CONCLUSION: Unmet needs remain after basal insulin initiation, particularly in real-world settings, where many patients require further insulin titration. In both populations, patients failing to achieve the target A1C despite attaining an FPG <130 mg/dL require interventions to improve postprandial control.

Treatment patterns and characteristics of patients with migraine in Japan: A retrospective analysis of health insurance claims data.

OBJECTIVE: To describe treatment patterns of migraine patients in the Japan Medical Data Center (JMDC) database. METHODS: Patients aged ≥18 years with ≥1 inpatient or ≥2 outpatient migraine diagnoses, ≥1 outpatient diagnosis and ≥1 migraine-specific acute treatment (triptan or ergotamine), or ≥2 migraine-specific acute treatments from 1 May 2011 to 30 April 2014 were identified. Patients were required to be enrolled in a health plan for ≥1 year before and after the index date. The first migraine diagnosis or acute treatment defined the index date. Patients were stratified by the migraine treatments observed after the index date (i.e. migraine-specific acute treatment only [AT], prophylactic with or without migraine-specific acute treatment [PT], or no treatment [NT]) and described regarding the first migraine treatment regimen and subsequent treatment patterns during up to 1 year of follow-up. RESULTS: A total of 16,443 patients met the eligibility criteria (9873 AT, 3022 PT, and 3548 NT). AT patients had mean (SD) 10.3 (20.5) acute treatment days during 1-year follow-up, and 81.9% received triptans. When assessing the first migraine treatment regimen during follow-up in PT patients, 29.2% received prophylactic treatment only and 51.7% received both acute and prophylactic treatment. Calcium-channel blockers with or without concomitant triptans (34.4%) were the most common first regimen. Approximately 62.2% discontinued initial prophylactic treatment after an average of 61.2 days (SD = 65.3) of persistent treatment. Among discontinuers, 15.2% reinitiated original treatment and 7.0% switched treatment post-discontinuation within a year, while the remaining patients did not receive prophylactic therapy following discontinuation. CONCLUSIONS: Among Japanese migraine patients, prophylactic use was low and associated with a high rate of discontinuation following a brief treatment period. Many patients reinitiated or switched treatment following discontinuation, while a significant proportion of patients remained discontinued from prophylactic therapy, suggesting a high unmet need.

Treatment patterns, survival and economic outcomes in Medicare-enrolled, older patients with HR+/HER2- metastatic breast cancer.

Background: Endocrine therapy (ET) remains a foundation of systemic therapy for HR+/ HER2- metastatic breast cancer (MBC), although chemotherapy (CT) is used in select patients. In this "real-world" study, we explored treatment patterns, health care resource use (HCRU), costs, adverse events (AEs) and overall survival (OS) in Medicare-enrolled, older patients with HR+/HER2- MBC. Methods: Patients with HR+/HER2- MBC (2007-2011) and aged >66 years were retrospectively analyzed using the SEER-Medicare data. Treatment patterns, HCRU, costs, AEs and OS after MBC diagnosis through end of study period (31 December 2013) were examined using descriptive and multivariable analyses. Results: Among 3622 eligible patients, ET was the most common treatment (77%), followed by CT (50%), radiation (48%) and surgery (19%). The proportion of patients treated with ET monotherapy decreased across therapy lines, from 74% in first line (1 L) to 35% in 4 L. The total number of unique therapy regimens used was 181 in 1 L, 171 in 2 L, 128 in 3 L, and 95 in 4 L. The median OS from MBC diagnosis was 25.3 months (95% CI, 24.0-26.7). In multivariable analyses, receipt of CT and combination CT + ET (versus ET monotherapy) in 1 L, metastatic disease at initial diagnosis, larger tumor size, and presence of visceral and brain metastases at MBC diagnosis significantly predicted receipt of 2 L therapy. Conclusions: ET was the most common first-line treatment for study patients, but its use decreased gradually in the subsequent lines. The heterogeneity in the treatment selection highlights a lack of consensus for the management of HR+/HER2- MBC in routine practice.