Propensity score matching for estimating a marginal hazard ratio.

Propensity score matching is commonly used to draw causal inference from observational survival data. However, its asymptotic properties have yet to be established, and variance estimation is still open to debate. We derive the statistical properties of the propensity score matching estimator of the marginal causal hazard ratio based on matching with replacement and a fixed number of matches. We also propose a double-resampling technique for variance estimation that takes into account the uncertainty due to propensity score estimation prior to matching.

Treatment patterns and outcomes associated with sequential and non-sequential use of CDK4 & 6 inhibitors in patients with HR+, HER2- MBC in the real world.

PURPOSE: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear. METHODS: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression. RESULTS: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2. CONCLUSIONS: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment.

Real-world ramucirumab and immune checkpoint inhibitor sequences in US patients with advanced gastroesophageal cancer.

Aim: To describe real-world treatment sequences of ramucirumab relative to immune checkpoint inhibitors (ICIs) in patients with advanced gastroesophageal cancer. Methods: Retrospective, observational study including adult patients treated with ramucirumab (April 2014-June 2020) from a nationwide health-record database. Results: In 1117 eligible patients, ramucirumab + paclitaxel was the most common ramucirumab-containing regimen (72.0%). A total of 217 patients also received an ICI. For ramucirumab then ICI (n = 148) and ICI then ramucirumab (n = 50), ramucirumab + taxane and ICI monotherapy were the most frequent approaches, most commonly observed as second- and third-line (2L and 3L). Median time on ramucirumab in 2L and 3L was similar regardless of sequence with ICI. Conclusion: Most patients with advanced gastroesophageal cancer received ramucirumab before ICI, with ramucirumab + paclitaxel as the most common ramucirumab-based regimen.

What is the Order of New Treatments for Gastroesophageal Cancers in the Real World? What is this summary about? Gastroesophageal cancers (cancers of the stomach or food pipe) which cannot be cured are first treated using traditional chemotherapy. Newer anti-cancer therapies with fewer side effects, such as ramucirumab (RAM) and immune checkpoint inhibitors (ICI), are now available either alone or in combination with chemotherapy. We designed this study to describe the order of use for RAM and ICI. What were the results? The patients in this study were from Flatiron Health database, which includes electronic medical record data of US patients with gastroesophageal cancers. The included patients had been treated with RAM and were grouped based on the treatments received and in the order in which they received RAM and ICI. Of the patients who received both RAM and ICI, RAM then ICI was the most common order, followed by ICI then RAM and then RAM plus ICI at the same time. RAM in combination with paclitaxel (a chemotherapy) was the most common RAM-containing treatment. The duration of RAM therapy was the same whether patients received the treatment before or after ICI. What do results of the study mean? These findings can be used by patients with gastroesophageal cancers and oncologists when making treatment decisions, specifically if RAM might be an option when it is time to change treatments. Real-world studies like this help answer questions that were not addressed in clinical trials.

A real-world US study of recurrence risks using combined clinicopathological features in HR-positive, HER2-negative early breast cancer.

Aim: To assess invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, HER2-negative early breast cancer with combined clinicopathological criteria from monarchE, a phase III study of abemaciclib. Methods: US electronic health records were used to compare outcomes between high-risk (≥4 lymph nodes, or 1-3 lymph nodes and grade 3, tumor ≥5 cm or Ki-67 ≥20%) versus nonhigh-risk groups using Kaplan-Meier methods and Cox regression models. Results: The high-risk group (n = 557) was at higher risk for IDFS and DRFS events than the nonhigh-risk group (n = 3471). IDFS events (hazard ratio: 3.07; 95% CI: 2.45-3.83) and DRFS events (hazard ratio: 3.15; 95% CI: 2.49-3.97) were significantly higher for the high-risk group. Conclusion: Risk of recurrence was three-times greater in the high-risk group, highlighting the need for better therapies.

Breast cancer is frequently diagnosed early, at a stage when patients can be cured. However, some patients have breast cancers (tumors) with a high risk of recurrence. When cancers come back, a cure is often not possible. This study looks at multiple high-risk tumor features and the risk of cancer returning, in the most common breast cancer type, known as hormone receptor-positive, HER2-negative breast cancer. In patients with high-risk tumors, breast cancer returned in about 11.9% of patients within 2 years and in 29.8% of patients at 5 years. The risk of recurrence or death was three-times higher in patients with high-risk tumors compared to patients with nonhigh-risk tumors. These results suggest better treatments are needed to prevent breast cancers from coming back in patients at high risk of recurrence.

Generalizability of ORIENT-11 trial results to a US standard-of-care cohort with advanced non-small-cell lung cancer.

Aim: This retrospective study estimated efficacy and safety of sintilimab + pemetrexed + platinum (SPP) versus placebo + pemetrexed + platinum (PPP) in untreated locally advanced/metastatic, nonsquamous non-small-cell lung cancer (NSCLC), after adjusting each ORIENT-11 trial patient's contribution to ORIENT-11 data based on characteristics of a target US population. Materials & methods: The target US population (n = 557) was selected from a real-world deidentified advanced NSCLC database based on key ORIENT-11 eligibility criteria. Inverse probability weights for ORIENT-11 patients (n = 397) relative to US patients were calculated. Efficacy and safety of SPP versus PPP were adjusted by inverse probability weights. Results: After adjustment, progression-free survival remained superior for SPP. Other efficacy and safety outcomes were consistent. Conclusion: These results provide evidence on how the effects observed with SPP in ORIENT-11 could translate to a US population with untreated locally advanced/metastatic nonsquamous NSCLC.

Sintilimab is an immunotherapy drug that was successfully developed and tested in China for untreated locally advanced/metastatic nonsquamous non-small-cell lung cancer. To assess if results from the Chinese ORIENT-11 trial are applicable to the US population, this study used US real-world patient data to adjust the ORIENT-11 trial analysis. After adjustment, progression-free survival benefit observed in ORIENT-11 with the addition of sintilimab to standard chemotherapy remained superior, and other efficacy and safety end points were consistent. This finding may help inform clinical decisions about the applicability of ORIENT-11 trial results to US patients with untreated locally advanced/metastatic nonsquamous NSCLC. In addition, this study offers another way real-world evidence can be applied to help complement clinical trial evidence and optimize treatment decisions.

Defining treatment regimens and lines of therapy using real-world data in oncology.

Retrospective observational research relies on databases that do not routinely record lines of therapy or reasons for treatment change. Standardized approaches to estimate lines of therapy were developed and evaluated in this study. A number of rules were developed, assumptions varied and macros developed to apply to large datasets. Results were investigated in an iterative process to refine line of therapy algorithms in three different cancers (lung, colorectal and gastric). Three primary factors were evaluated and included in the estimation of lines of therapy in oncology: defining a treatment regimen, addition/removal of drugs and gap periods. Algorithms and associated Statistical Analysis Software (SAS®) macros for line of therapy identification are provided to facilitate and standardize the use of real-world databases for oncology research.

Lay abstract Most, if not all, real-world healthcare databases do not contain data explaining treatment changes, requiring that rules be applied to estimate when treatment changes may reflect advancement of underlying disease. This study investigated three tumor types (lung, colorectal and gastric cancer) to develop and provide rules that researchers can apply to real-world databases. The resulting algorithms and associated SAS^® macros from this work are provided for use in the Supplementary data.

Healthcare resource utilization in advanced non-small-cell lung cancer: post hoc analysis of the randomized phase 3 REVEL study.

PURPOSE: In REVEL, patients with advanced non-small-cell lung cancer (aNSCLC) and patients with increased tumor aggressiveness (rapid disease progression (RDP), platinum-refractory disease (PRD), and high symptom burden (HSB)) benefited from second-line treatment with ramucirumab plus docetaxel over placebo plus docetaxel. This post hoc analysis describes healthcare resource utilization (HCRU) associated with the treatment. METHODS: aNSCLC patients who had progressed during or after first-line platinum-based chemotherapy were randomized to receive docetaxel and either ramucirumab or placebo until disease progression, unacceptable toxicity, withdrawal, or death. HCRU included hospitalizations, transfusions, and concomitant medications. Categorical variables (counts and percentages) were compared using Fisher's exact test. Continuous variables (mean, standard deviation (SD), median, minimum, and maximum) were compared using the Wilcoxon rank sum test. RESULTS: Patient characteristics were largely similar between treatment arms. Within the intent-to-treat (ITT) population (n = 1253), the mean treatment duration was 19.7 and 16.9 weeks in the ramucirumab and control arms, respectively; 51.0% versus 54.9% of patients received subsequent anticancer therapy, respectively. Hospitalization rates were 41.9% versus 42.6% (p = 0.863), mean length of hospital stay was 14.5 days versus 11.3 days (p = 0.066), transfusion rates were 9.9% versus 12.3% (p = 0.206), and use of granulocyte colony-stimulating factors was 41.8% versus 36.6% (p = 0.063), respectively. No significant difference was observed in HCRU between treatment arms in both ITT population and in aggressive disease subgroups including RDP (n = 209), PRD (n = 360), and HSB (n = 497). CONCLUSION: In REVEL, the addition of ramucirumab to docetaxel did not increase HCRU among patients with aggressive aNSCLC disease. These results may help inform economic evaluation of treatment for patients with aNSCLC.

Treatment patterns and survival outcomes for patients receiving second-line treatment for metastatic colorectal cancer in the USA.

BACKGROUND: Colorectal cancer is the third most common cause of cancer death in the USA. It is important to identify patients who may experience poor outcomes from available treatments. METHODS: In this retrospective observational study, treatment patterns and survival outcomes were described among adult patients from the Flatiron Health electronic medical records database who were treated with at least two lines of therapy for metastatic colorectal cancer in the USA between January 2013 and May 2018. Patients with rapid progression were defined as those whose time from start of first- to second-line therapy was ≤ 183 days. RESULTS: A total of 14,315 patients formed the study cohort. The most common first-line treatments were FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) plus bevacizumab, received by 34.7% (n = 4962) of patients, followed by FOLFOX alone (17.1%, n = 2445). Of all patients, 6991 (48.9%) also received second-line anti-cancer therapy and of those, 3338 (47.7%) had rapid progression and 3653 (52.3%) did not. Median overall survival from the start of first- and second-line therapy was 20.8 months (95% CI 20.2-21.3) and 14.5 months (95% CI 13.9-15.0) for the entire study population, respectively. Median overall survival from the start of second-line therapy was 14.1 (95% CI 13.2-14.8) for patients with rapid progression and 14.6 months (95% CI 13.8-15.4) for patients without rapid progression. CONCLUSIONS: Patients diagnosed with metastatic colorectal cancer lived less than 2 years in this real-world database. While the time to initiation of second-line therapy was by definition longer among patients without rapidly progressing disease, survival outcomes were comparable from initiation of second-line therapy.

Sequential therapy with ramucirumab and/or checkpoint inhibitors for non-small-cell lung cancer in routine practice.

Aim: To describe treatment patterns and outcomes for advanced/metastatic non-small-cell lung cancer (aNSCLC) treated with single-agent or combination ramucirumab (ramucirumab-based) and/or immune checkpoint inhibitor (ICI-based) therapy. Materials & methods: Retrospective study of aNSCLC patients (n = 4054) identified in the Flatiron Health database, who received at least two treatment lines including ramucirumab- and/or ICI-based regimens between December 2014 and May 2017. Results: Median overall survival (95% CI) from aNSCLC diagnosis was 29.3 (25.5-33.0) months for patients receiving sequential ramucirumab- and ICI-based therapy (n = 245), 15.1 (12.6-18.2) months for patients receiving sequences including ramucirumab- without ICI-based therapy (n = 112), and 23.1 (21.9-24.2) months for patients receiving ICI-based therapy without ramucirumab-based therapy in sequence (n = 3697). Conclusion: Results provide real-world survival estimates for aNSCLC treated with sequences including ramucirumab- and/or ICI-based therapies.

Ramucirumab for the treatment of patients with gastric or gastroesophageal junction cancer in community oncology practices.

BACKGROUND: Limited real-world research has investigated ramucirumab for the treatment of patients with gastric or gastroesophageal junction (GEJ) cancer. This study was designed to describe ramucirumab monotherapy or combination therapy use in a community oncology practice setting. METHODS: This was a retrospective observational cohort study to describe the treatment of adult patients with gastric or GEJ cancer who initiated ramucirumab treatment between 4/21/14 and 6/30/16 within the US Oncology Network. Kaplan-Meier method and Cox proportional hazards regression analyses were used to assess clinical outcomes. Multivariable logistic regression models were used to assess patient-level predictors of ramucirumab monotherapy or combination therapy. RESULTS: A total of 505 patients (mean age 64.4 years; 75.1% male) were included in the analysis; subgroups included: monotherapy (22.8%; n = 115), combination therapy (77.2%; n = 390). Monotherapy patients were significantly older (67.7 vs. 63.4 years; P = 0.0006), received ramucirumab approximately 3 months later after diagnosis (16.9 vs. 14.1 months; P = 0.0318) and more frequently initiated ramucirumab in the third or later lines of treatment (38.3 vs. 8.2%; P<0.0001) than patients receiving combination therapy. Median overall survival (OS) for monotherapy and combination therapy from the start of second-line therapy was 5.5 months (confidence interval [CI] 4.3, 7.8) and 7.4 months (CI 6.6, 8.8), respectively. CONCLUSIONS: The results showed that patients who received ramucirumab monotherapy started ramucirumab therapy later after diagnosis and were older than those who received ramucirumab in combination. Additionally, survival data suggest that outcomes observed in community oncology practices are similar to data from phase 3 clinical trials.

Propensity score matching and subclassification in observational studies with multi-level treatments.

In this article, we develop new methods for estimating average treatment effects in observational studies, in settings with more than two treatment levels, assuming unconfoundedness given pretreatment variables. We emphasize propensity score subclassification and matching methods which have been among the most popular methods in the binary treatment literature. Whereas the literature has suggested that these particular propensity-based methods do not naturally extend to the multi-level treatment case, we show, using the concept of weak unconfoundedness and the notion of the generalized propensity score, that adjusting for a scalar function of the pretreatment variables removes all biases associated with observed pretreatment variables. We apply the proposed methods to an analysis of the effect of treatments for fibromyalgia. We also carry out a simulation study to assess the finite sample performance of the methods relative to previously proposed methods.

Use of Hormone Testing for the Diagnosis and Evaluation of Male Hypogonadism and Monitoring of Testosterone Therapy: Application of Hormone Testing Guideline Recommendations in Clinical Practice.

INTRODUCTION: Clinical practice guidelines recommend that testosterone (T) levels be measured on ≥2 occasions to confirm a diagnosis of hypogonadism, gonadotropins be measured to determine whether hypogonadism is primary or secondary, and T levels be measured to monitor the adequacy of T therapy. However, it is not known whether hormone testing as recommended by guidelines is routinely performed in real-world clinical practice. AIM: The aim of this study was to assess the use of hormone testing for the diagnosis and evaluation of hypogonadism and monitoring of T therapy in clinical practice. METHODS: In this retrospective cohort study of the Truven Health Marketscan(®) Commercial and Medicare Supplemental Insurance Databases during 2010-2012, 63,534 men over 18 years old who received T therapy and had continuous medical benefit enrollment for 1 year prior to and 6 months after T therapy initiation were included in this analysis. MAIN OUTCOME MEASURES: Proportion of patients who received ≥2, 1, or no T-level determinations prior to or following T therapy initiation. RESULTS: Seventy-one percent of hypogonadal men had T measured at least once and 40% had ≥ 2 tests, but only 12% of men had luteinizing hormone and/or follicle-stimulating hormone levels measured prior to T therapy initiation. Following T therapy initiation, 46% had ≥1 follow-up T measurements. CONCLUSIONS: Appropriate use of T and gonadotropin levels in clinical practice as recommended by guidelines is suboptimal, increasing the possibility of overdiagnosis of male hypogonadism, underdiagnosis of secondary hypogonadism, and inappropriate T therapy use and management. Further investigation is needed into reasons for nonadherence to guidelines for appropriate hormone testing to inform future quality improvement efforts.

Long-term treatment patterns of testosterone replacement medications.

INTRODUCTION: Testosterone replacement therapy (TRT) is prescribed to men diagnosed with hypogonadism to alleviate symptoms, improve quality of life, and improve overall health. However, most men use TRT for only a short duration. AIM: To evaluate the long-term treatment patterns in hypogonadal men using topical TRT or short-lasting TRT injections. METHODS: Using the Truven MarketScan(®) Database, 15,435 men who received their first (index) topical TRT prescription and 517 men who received their short-lasting TRT injection index prescription in 2009 were followed from 12 to 30 months after treatment initiation. Treatment interruption was defined as a medication gap of >30 days. Patients who remained off treatment were classified as having discontinued treatment. Patients who restarted therapy after 30 days were classified as cyclic users. Patients were required to have continuous insurance coverage during 1 year prior to treatment initiation and at least 1 year afterward. MAIN OUTCOME MEASURES: Main outcome measures were length of therapy, discontinuation, and restarts of topical TRT or short-lasting TRT injections. RESULTS: The patient characteristics were similar for patients who received topical TRT or short-lasting TRT injections. Of the patients who discontinued therapy during the follow-up period, the percentages of patients who were still on therapy after 3 months were 52% and 31% for topical TRT and short-lasting TRT users, respectively. For cyclic users, there was an attrition rate of approximately 40% to 50% of patients in each cycle. For both topical TRT and short-lasting TRT injections, the gap between stopping and restarting therapy tended to decrease over time. CONCLUSIONS: In this analysis, high discontinuation rates were observed. The treatment pattern of TRT may be related to the disease state rather than dosing, daily use, or mode of administration.

Medication adherence and treatment patterns for hypogonadal patients treated with topical testosterone therapy: a retrospective medical claims analysis.

INTRODUCTION: There is limited information on adherence to topical testosterone replacement therapy (TRT) among hypogonadal men. AIM: To determine adherence rates among men treated with topical testosterone gels and to examine factors that may influence adherence, including age, presence of a specific diagnosis, and index dose. METHODS: Included were 15,435 hypogonadal men, from the Thomson Reuters MarketScan Database, who had an initial topical testosterone prescription in 2009 and who were followed for 12 months. MAIN OUTCOME MEASURES: Adherence to testosterone was measured by medication possession ratio (MPR), with high adherence defined as ≥0.8. Persistence was defined as the duration of therapy from the index date to the earliest of the following events: end date of the last prescription, date of the first gap of >30 days between prescriptions, or end of the study period (12 months). RESULTS: Adherence to topical TRT was low. By 6 months, only 34.7% of patients had continued on medication; at 12 months, only 15.4%. Adherence rates were numerically similar among men who received AndroGel or Testim topical gels and did not differ among men of different age groups. Approximately 80% of patients initiated at the recommended dose of 50 mg/day. Over time, an increased proportion of men used a higher dose. This change was the result of dose escalation, rather than of greater adherence among men initiating therapy at a high dose. Dose escalation was seen as early as 1 month into therapy. Approximately 50% of men who discontinued treatment resumed therapy; most men used the same medication and dose. CONCLUSIONS: Discontinuation rates are high among hypogonadal men treated with testosterone gels, irrespective of their age, diagnosis, and index dose. Further study, evaluating other measurable factors associated with low adherence among patients receiving topical TRT, may lead to interventions designed to improve adherence with therapy.

Empirically driven definitions of "good," "moderate," and "poor" levels of functioning in the treatment of schizophrenia.

PURPOSE: This study used an empirical approach to identify and validate the classification of patients with schizophrenia in "good," "moderate," or "poor" functioning groups based on the assessment of functional measures. METHODS: Using data from a study of schizophrenia outpatients, patients were classified into functional groups using cluster analysis based on the Heinrich-Carpenter Quality of Life Scale (QLS), the 36-item Short-Form Health Survey (SF-36) Mental Component Summary Score, and a productivity measure. A three-cluster solution was chosen. Concurrent, convergent, and discriminant validity were assessed. Criteria for classifying patient functioning as "good," "moderate," or "poor" were established using classification and regression tree analysis. RESULTS: The three clusters consistently differentiated patients on the QLS, SF-36 Mental Component Summary Score, and productivity measure. The clusters also differed on other functional measures and were concordant with previous functional classifications. Concurrent, convergent, and discriminant validity were good. "Good" functioning was identified as a QLS total score ≥ 84.5; "moderate" and "poor" functioning were separated by a cutoff score of 15.5 on the QLS intrapsychic foundation domain. Sensitivity ranged from 86 to 93 % and specificity from 89 to 99 %. CONCLUSIONS: The heterogeneity in functioning of schizophrenia patients can be classified reliably in an empirical manner using specific cutoff scores on commonly used functional measures.

Relationship between muscle mass and muscle strength, and the impact of comorbidities: a population-based, cross-sectional study of older adults in the United States.

BACKGROUND: Loss of muscle mass and muscle strength are natural consequences of the aging process, accompanied by an increased prevalence of chronic health conditions. Research suggests that in the elderly, the presence of comorbidities may impact the muscle mass/strength relationship. The objectives of this study were to characterize the muscle mass/strength relationship in older adults in the USA and to examine the impact of a variety of comorbidities on this relationship. METHODS: Data were obtained from the National Health and Nutrition Examination Survey 1999-2002 databases. Subjects aged 50 years and older were included in the present study. Muscle mass was assessed by height-adjusted appendicular skeleton muscle mass (aASM) in kg/m2, as measured by dual-energy x-ray absorptiometry. Muscle strength was assessed via isokinetic quadriceps strength (IQS) in newton as measured by a dynamometer. The relationship between aASM and IQS was assessed adjusting for age and gender. The effects of a variety of comorbidities on IQS and/or on the relationship between IQS and aASM were assessed using multiple regression models. RESULTS: This study included 2,647 individuals, with a mean age of 62.6 years and 52.9% of whom were female. The mean (SE) aASM (kg/m2) was 7.3 (0.04), and the mean (SE) IQS (newton) was 365.0 (3.00). After adjusting for age and gender, the correlation coefficient between aASM and IQS was 0.365 (P < 0.001). Diabetes, coronary heart disease/congestive heart failure (CHD/CHF), and vision problems were significant predictors of lower muscle strength (P < 0.05) in the multiple regression models that adjusted for age, gender, and aASM, and obesity significantly modified the relationship between aASM and IQS (P < 0.05). CONCLUSIONS: Among individuals aged 50 and older in the US, muscle mass and muscle strength are positively correlated, independent of the associations of age and gender with muscle mass and strength. A variety of comorbid medical conditions serve as independent predictors of lower muscle strength (e.g., diabetes, CHD/CHF, vision problems) and/or modify the relationship between muscle mass and muscle strength (e.g., obesity).

Real-world comparison between weekly versus biweekly dosing of cetuximab for metastatic colorectal cancer.

Aim: This real-world study aims to compare overall survival (OS) associated with biweekly (Q2W) versus weekly (Q1W) cetuximab dosing regimens for metastatic colorectal cancer (mCRC) treatment in the US. Methods: Adult patients with KRAS wild-type mCRC who received cetuximab ± chemotherapy from 2013 to 2019 were selected using Flatiron Health's electronic health records database. Propensity score matching was used to balance Q2W and Q1W cohorts on baseline patient characteristics. The Kaplan-Meier method was used for survival analyses. Several sensitivity analyses were conducted to assess the robustness of findings from the main analysis. Results: Of 1075 patients in the study, 60.7% received cetuximab Q1W and 39.3% Q2W. Median OS (95% confidence interval) in months was 17.2 (15.3, 18.8) for Q2W versus 14.3 (12.8, 16.0) for Q1W; p = 0.246. Similar OS between the dosing cohorts was observed in sensitivity analyses. Conclusion: Weekly and biweekly cetuximab had comparable effectiveness in this real-world study.

Characteristics and Outcomes in Cases of US Male Patients with Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking. METHODS: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). RESULTS: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD. CONCLUSION: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting.

Real-World Analysis of Clinical and Demographic Characteristics, Treatment Patterns, and Outcomes in Predominantly Older Patients with HR+/HER2- Metastatic Breast Cancer Receiving Abemaciclib in Routine Clinical Practice.

INTRODUCTION: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients. METHODS AND MATERIALS: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes. RESULTS: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation. CONCLUSIONS: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC.

Study of patient characteristics, treatment patterns, EGFR testing patterns and outcomes in real-world patients with EGFRm+ non-small cell lung cancer.

OBJECTIVE: This retrospective, observational study examined patient characteristics, treatment patterns, testing patterns, and outcomes of US patients receiving first-/second- or third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). METHODS: This study used an electronic health record-derived de-identified database. Eligible patients had advanced EGFRm+ non-small cell lung cancer. Descriptive statistics were used to describe demographic, clinical, and treatment characteristics. Logistic regression models were used to identify patient characteristics that were associated with the use of osimertinib vs. a first-/second-generation EGFR TKI. Kaplan-Meier methods were used for survival analysis. RESULTS: Of the 782 patients who received first-line (1L) therapy with first-/second-generation EGFR TKIs in cohort A, erlotinib was the most common (58%), and osimertinib was the most widely prescribed second-line (2L) therapy (52%). Of the patients who received 1L therapy with osimertinib, a greater range of treatments were prescribed in 2L. A third of patients treated with first-/second-generation EGFR TKIs underwent EGFR testing near the end of 1L, and 44% of these patients had T790M positive disease. The median time on targeted therapy (TTT) of the cohort was 11.1 months (95% confidence interval [CI] 9.7, 12.3), and the median overall survival from the start of 1L therapy was 23.5 months (95% CI 20.7, 24.8). CONCLUSIONS: The majority of patients treated with first-/second-generation EGFR TKIs went on to receive osimertinib in the 2L setting, but overall, only a third of patients had received molecular testing at progression. Improved testing frequency is vital to inform treatment decisions.