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.

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.

Clinicogenomic factors and treatment patterns among patients with advanced non-small cell lung cancer with or without brain metastases in the United States.

BACKGROUND: This retrospective, real-world study evaluated the prevalence of brain metastases, clinicodemographic characteristics, systemic treatments, and factors associated with overall survival among patients with advanced non-small cell lung cancer (aNSCLC) in the US. We also described the genomic characterization of 180 brain metastatic specimens and frequency of clinically actionable genes. MATERIALS AND METHODS: De-identified electronic health records-derived data of adult patients diagnosed with aNSCLC between 2011 and 2017 were analyzed from a US-nationwide clinicogenomic database. RESULTS: Of 3257 adult patients with aNSCLC included in the study, approximately 31% (n = 1018) had brain metastases. Of these 1018 patients, 71% (n = 726) were diagnosed with brain metastases at initial NSCLC diagnosis; 57% (n = 583) of patients with brain metastases received systemic treatment. Platinum-based chemotherapy combinations were the most common first-line therapy; single-agent chemotherapies, epidermal growth factor receptor tyrosine kinase inhibitors, and platinum-based chemotherapy combinations were used in second line. Patients with brain metastases had a 1.56 times greater risk of death versus those with no brain metastases. In the brain metastatic specimens (n = 180), a high frequency of genomic alterations in the p53, MAPK, PI3K, mTOR, and cell-cycle associated pathways was observed. CONCLUSION: The frequency of brain metastases at initial clinical presentation and associated poor prognosis for patients in this cohort underscores the importance of early screening for brain metastasis in NSCLC. Genomic alterations frequently identified in this study emphasize the continued need for genomic research and investigation of targeted therapies in patients with brain metastases.

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.

Development and Validation of Coding Algorithms to Identify Patients with Incident Non-Small Cell Lung Cancer in United States Healthcare Claims Data.

Purpose: We sought to develop and validate an incident non-small cell lung cancer (NSCLC) algorithm for United States (US) healthcare claims data. Diagnoses and procedures, but not medications, were incorporated to support longer-term relevance and reliability. Methods: Patients with newly diagnosed NSCLC per Surveillance, Epidemiology, and End Results (SEER) served as cases. Controls included newly diagnosed small-cell lung cancer and other lung cancers, and two 5% random samples for other cancer and without cancer. Algorithms derived from logistic regression and machine learning methods used the entire sample (Approach A) or started with a previous algorithm for those with lung cancer (Approach B). Sensitivity, specificity, positive predictive values (PPV), negative predictive values, and F-scores (compared for 1000 bootstrap samples) were calculated. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. Results: The best performing algorithm utilized neural networks (Approach B). A 10-variable point-score algorithm was derived from logistic regression (Approach B); sensitivity was 77.69% and PPV = 67.61% (F-score = 72.30%). This algorithm was less sensitive for patients ≥80 years old, with Medicare follow-up time <3 months, or missing SEER data on stage, laterality, or site and less specific for patients with SEER primary site of main bronchus, SEER summary stage 2000 regional by direct extension only, or pre-index chronic pulmonary disease. Conclusion: Our study developed and validated a practical, 10-variable, point-based algorithm for identifying incident NSCLC cases in a US claims database based on a previously validated incident lung cancer algorithm.

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.

The Burden of Metastatic Cancer-Induced Bone Pain: A Narrative Review.

Bone pain is one of the most common forms of pain reported by cancer patients with metastatic disease. We conducted a review of oncology literature to further understand the epidemiology of and treatment approaches for metastatic cancer-induced bone pain and the effect of treatment of painful bone metastases on the patient's quality of life. Two-thirds of patients with advanced, metastatic, or terminal cancer worldwide experience pain. Cancer pain due to bone metastases is the most common form of pain in patients with advanced disease and has been shown to significantly reduce patients' quality of life. Treatment options for cancer pain due to bone metastases include nonsteroidal anti-inflammatory drugs, palliative radiation, bisphosphonates, denosumab, and opioids. Therapies including palliative radiation and opioids have strong evidence supporting their efficacy treating cancer pain due to bone metastases; other therapies, like bisphosphonates and denosumab, do not. There is sufficient evidence that patients who experience pain relief after radiation therapy have improved quality of life; however, a substantial proportion are nonresponders. For those still requiring pain management, even with available analgesics, many patients are undertreated for cancer pain due to bone metastases, indicating an unmet need. The studies in this review were not designed to determine why cancer pain due to bone metastases was undertreated. Studies specifically addressing cancer pain due to bone metastases, rather than general cancer pain, are limited. Additional research is needed to determine patient preferences and physician attitudes regarding choice of analgesic for moderate to severe cancer pain due to bone metastases.

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting.

OBJECTIVE: To examine the real-world incidence and management of select adverse events (AEs) among female patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), receiving a cyclin-dependent kinase 4 and 6 (CDK4 and 6) inhibitor (palbociclib, abemaciclib, or ribociclib). METHODS: This retrospective study analyzed data from the US Oncology Network iKnowMed electronic health record database for 396 patients with an initial MBC diagnosis on/after 1 January 2014 and receipt of first CDK4 and 6 regimen between 1 January 2017 and 31 December 2018. In this descriptive study, the proportion of patients who experienced select AEs and associated dose modifications or discontinuations were reported. The occurrence of select healthcare resource utilization categories was also reported. RESULTS: Median follow-up time was 451, 262, and 355 days for patients in the palbociclib, abemaciclib, and ribociclib cohorts, respectively. The most common AEs were neutropenia (palbociclib, 44.8%; abemaciclib, 10.6%; ribociclib, 36.3%), diarrhea (palbociclib, 8.0%; abemaciclib, 43.0%; ribociclib, 8.8%), and fatigue (palbociclib, 12.9%; abemaciclib, 17.6%; ribociclib, 16.5%). AEs resulted in a treatment hold among 91 (23.0%), a dose reduction among 86 (21.7%), and permanent discontinuation among 48 (12.1%) patients overall. CONCLUSIONS: This real-world study provides insight into the occurrence of AEs which varied by CDK4 and 6 inhibitor. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible these differences reflect proactive management of AEs on the part of clinicians to help patients remain on therapy.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4 and 6 inhibitors) have changed the landscape for the treatment of metastatic breast cancer (MBC) among patients who are hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2−). An understanding of the real-world management of adverse events (AEs) will help optimize treatment strategies. Here, data from the US Oncology Network electronic health record database for 396 HR+, HER2−, MBC patients receiving a CDK4 and 6 inhibitor were examined to describe the proportion of patients who experienced select AEs and the associated outcomes of these AEs. Compared to clinical trials, frequencies of AEs were numerically lower but dose reductions due to AEs were numerically higher. It is possible that these differences reflect a proactive management of AEs on the part of clinicians to help patients remain on therapy.

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.

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.

Real-world treatment patterns and outcomes of abemaciclib for the treatment of HR+, HER2- metastatic breast cancer.

OBJECTIVE: This retrospective observational study described baseline characteristics, real-world treatment patterns, and outcomes among patients with metastatic breast cancer treated with abemaciclib in the United States. METHODS: De-identified electronic health record-derived data were used to describe patients who began abemaciclib treatment on or after 30 June 2016 and ≥4 months before data cutoff (31 December 2018). Real-world response (rwR) and real-world progression assessments were abstracted from clinical documentation. Descriptive statistics were used to calculate the real-world best response. The Kaplan-Meier method estimated real-world time to first response (rwTTFR) and real-world progression-free survival (rwPFS). RESULTS: The median age of 118 female patients at abemaciclib initiation was 66.5 years (interquartile range, 57.0, 73.0). The breakdown of patients who received abemaciclib in first, second, third, or later lines was 28.8%, 21.2%, 20.3%, and 29.7%, respectively. Patients received abemaciclib as monotherapy (12.7%) or in combination with endocrine therapy: fulvestrant (59.3%); aromatase inhibitor (22.9%); aromatase inhibitor and fulvestrant (5.1%). There were 68 patients (57.6%) with ≥1 rwR assessment: 41.2% with a real-world complete response or real-world partial response. Median rwTTFR was 3.6 months (95% confidence interval, 3.5, 5.2). Twelve-month rwPFS probability was 61.7%. CONCLUSIONS: This study represents utilization and outcomes associated with abemaciclib approximately 1 year following FDA approval. Treatment patterns demonstrated heterogeneity and, as in clinical trials, patients appeared to benefit from abemaciclib treatment in the real world. More research investigating outcomes associated with abemaciclib treatment is needed, with larger samples and longer follow-up to enable closer evaluation by subgroup, regimen, and line of therapy.

Predicting optimal treatment regimens for patients with HR+/HER2- breast cancer using machine learning based on electronic health records.

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2- MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios = 0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2- MBC.

Development and validation of coding algorithms to identify patients with incident lung cancer in United States healthcare claims data.

PURPOSE: Our aim was to develop and validate a practical US healthcare claims algorithm for identifying incident lung cancer that improves on positive predictive value (PPV) and sensitivity observed in past studies. METHODS: Patients newly diagnosed with lung cancer in Surveillance, Epidemiology, and End Results (SEER) (gold standard) were linked with Medicare claims. A 5% Medicare "other cancer" sample and noncancer sample served as controls. A split-sample validation approach was used. Rules-based, regression, and machine learning models for developing algorithms were explored. Algorithms were developed in the model building subset. Rules-based algorithms and those with the highest F scores were evaluated in the validation subset. F scores were compared for 1000 bootstrap samples. Misclassification was evaluated by calculating the odds of selection by the algorithm among true positives and true negatives. RESULTS: A practical single-score algorithm derived from a logistic regression model had sensitivity = 78.22% and PPV = 78.50% (F score: 78.36). The algorithm was most likely to misclassify older patients (ages ≥80 years) or with missing data in the SEER registry, shorter follow-up time in Medicare (<3 months), insurance through Veterans Affairs, >1 cancer in SEER, or certain Charlson comorbidities (dementia, chronic pulmonary disease, liver disease, or myocardial infarction). CONCLUSION: In this dataset, a practical point-based algorithm for identifying incident lung cancer demonstrated significant and substantial improvement (7.9% and 23.9% absolute improvement in sensitivity and PPV, respectively) compared with a current standard.

Replication of randomized clinical trial results using real-world data: paving the way for effectiveness decisions.

The FDA is preparing guidance about using real-world evidence (RWE) to support decisions about product effectiveness. Several ongoing efforts aim to replicate randomized clinical trial (RCT) results using RWE with the intent of identifying circumstances and methods that provide valid evidence of drug effects. Lack of agreement may not be due to faulty methods but rather to the challenges with emulating RCTs, differences in healthcare settings and patient populations, differences in effect measures and data analysis, bias, and/or the efficacy-effectiveness gap. In fact, for some decisions, RWE may lead to better understanding of how treatments work in usual care settings than a more constrained view from RCTs. Efforts to reconcile the role and opportunities for generating complementary evidence from RWE and RCTs will advance regulatory science.

Real-world survival outcomes of heavily pretreated patients with refractory HR+, HER2-metastatic breast cancer receiving single-agent chemotherapy-a comparison with MONARCH 1.

PURPOSE: In MONARCH 1 (NCT02102490), single-agent abemaciclib demonstrated promising efficacy activity and tolerability in a population of heavily pretreated women with refractory HR+, HER2- metastatic breast cancer (MBC). To help interpret these results and put in clinical context, we compared overall survival (OS) and duration of therapy (DoT) between MONARCH 1 and a real-world single-agent chemotherapy cohort. METHODS: The real-world chemotherapy cohort was created from a Flatiron Health electronic health records-derived database based on key eligibility criteria from MONARCH 1. The chemotherapies included in the cohort were single-agent capecitabine, gemcitabine, eribulin, or vinorelbine. Results were adjusted for baseline demographics and clinical differences using Mahalanobis distance matching (primary analysis) and entropy balancing (sensitivity analysis). OS and DoT were analyzed using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: A real-world single-agent chemotherapy cohort (n = 281) with eligibility criteria similar to the MONARCH 1 population (n = 132) was identified. The MONARCH 1 (n = 108) cohort was matched to the real-world chemotherapy cohort (n = 108). Median OS was 22.3 months in the abemaciclib arm versus 13.6 months in the matched real-world chemotherapy cohort with an estimated hazard ratio (HR) of 0.54. The median DoT was 4.1 months in MONARCH 1 compared to 2.9 months in the real-world chemotherapy cohort with HR of 0.76. CONCLUSIONS: This study demonstrates an approach to create a real-world chemotherapy cohort suitable to serve as a comparator for trial data. These exploratory results suggest a survival advantage and place the benefit of abemaciclib monotherapy in clinical context.

KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC. Relevant clinical trials and observational studies were identified by searching MEDLINE, Embase and Cochrane Register of Controlled Trials. Meta-analyses were performed using data extracted from multivariable and univariable analyses from clinical studies to assess the empirical evidence of KRAS mutation status as a prognostic or/and predicitive factor. 43 selected studies were identified by the SLR and included in this meta-analysis. Pairwise meta-analyses of hazard ratios (HRs) reported in randomized controlled trials (RCTs) did not demonstrate a significant prognostic effect of mutant KRAS on overall survival (OS) (HR=1.10; 95% CI [0.88, 1.38]) or progression free survival (PFS) (HR=1.03; 95% CI [0.80, 1.33]). However, when conducting meta-analyses on HRs reported in observational studies, a statistically significant negative prognostic effect of mutant KRAS was observed (OS HR=1.71; 95% CI [1.07, 2.84]; PFS HR=1.18; 95% CI [1.02, 1.36]). Meta-analyses of objective response rate (ORR) in RCTs demonstrated a negative prognostic effect of mutant KRAS (RR=0.38; 95% CI [0.16, 0.63]). Limited data were available to evaluate the role of KRAS mutation as a predictive factor. In conclusion, this research offers evidence that KRAS mutation may be a negative prognostic factor for survival and response outcomes in patients with advanced/metastatic NSCLC, but further research is needed to address conflicting results on the importance of KRAS mutations as a predictive factor.

Primary tumor location and survival in colorectal cancer: A retrospective cohort study.

BACKGROUND: Primary tumor location is a prognostic factor for metastatic colorectal cancer (mCRC). Post hoc analyses of mCRC clinical trials, including FIRE-3, CALGB/SWOG 80405, suggest that primary tumor location is also predictive of survival benefit with cetuximab or bevacizumab in combination with 5-fluorouracil-based chemotherapy. AIM: Evaluate prognostic/predictive roles of primary tumor location in real-world mCRC patients treated with cetuximab or bevacizumab plus 5-fluorouracil-based chemotherapy. METHODS: This retrospective cohort study selected patients with KRAS wild-type mCRC who initiated first-line therapy with cetuximab or bevacizumab in combination with 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) or 5-fluorouracil/ leucovorin/oxaliplatin (FOLFOX) between January 2013 and April 2017 from the Flatiron Health electronic health record-derived database of de-identified patient-level data in the United States. Primary tumor location was abstracted from patients' charts. Left-sided primary tumor location (LPTL) was defined as tumors that originated in the splenic flexure, descending colon, sigmoid colon, or rectum; right-sided primary tumor location (RPTL) was defined as tumors that originated from the appendix, cecum, ascending colon, hepatic flexure, or transverse colon. Propensity score matching was used to balance the baseline demographic and clinical characteristics between patients treated with cetuximab and patients treated with bevacizumab. Kaplan-Meier and Cox regression methods were used for survival analyses. RESULTS: A total of 1312 patients met the selection criteria. Of 248 cetuximab plus FOLFIRI or FOLFOX patients, 164 had LPTL and 84 had RPTL; of 1064 bevacizumab plus FOLFIRI or FOLFOX patients, 679 had LPTL and 385 had RPTL. Cetuximab LPTL and RPTL patients were more likely to receive FOLFIRI vs bevacizumab patients (LPTL: 64.0% vs 24.3%; RPTL: 76.2% vs 24.9%, P < 0.001). Stage at initial diagnosis was different between cetuximab RPTL vs bevacizumab RPTL patients (P < 0.001); cetuximab RPTL patients were more likely to have stage III disease (44.0% vs 22.6%), while bevacizumab RPTL patients were more likely to have stage IV disease (65.7% vs 48.8%). Cetuximab RPTL patients were more likely to have a documented history of adjuvant chemotherapy vs bevacizumab RPTL patients (47.6% vs 22.3%, P < 0.001). In the propensity score-matched sample, median overall survival (OS) was 29.7 mo (95%CI: 26.9-35.2) for LPTL patients vs 18.3 mo (95%CI: 15.8-21.3) for RPTL patients (P < 0.001). Median OS was 29.7 mo (95%CI: 27.4-NA) for cetuximab LPTL patients vs 29.1 mo (95%CI: 26.6-35.6) for bevacizumab LPTL patients (HR = 0.87; 95%CI: 0.63-1.19; P = 0.378) and 17.0 mo (95%CI: 12.0-32.6) for cetuximab RPTL patients vs 18.8 mo (95%CI: 15.8-22.3) for bevacizumab RPTL patients (HR = 1.00; 95%CI: 0.68-1.46; P = 0.996). The interaction of treatment and primary tumor location was not significant in the Cox regression. CONCLUSION: In this real-world mCRC cohort, the prognostic role of primary tumor location was substantiated, but not the predictive role for treatment with cetuximab vs bevacizumab in combination with 5-fluorouracil-based chemotherapy.

Perceptions of overdetection of breast cancer among women 70 years of age and older in the USA: a mixed-methods analysis.

OBJECTIVES: Current research on the perceptions of overdiagnosis or overdetection of breast cancer has largely been conducted outside of the USA and with women younger than 70 years.Therefore, we explored older women's perceptions about the concept of overdetection of breast cancer and its influence on future screening intentions. DESIGN: Mixed-methods analysis using purposive sampling based on race/ethnicity, age and educational level. Semistructured interviews, including two hypothetical scenarios illustrating benefits and harms of screening and overdetection, were analysed using inductive and deductive thematic approaches. An inferential clustering technique was used to assess overall patterns in narrative content by sociodemographic characteristics, personal screening preferences or understanding of overdetection. SETTING: Houston/Galveston, Texas, USA. PARTICIPANTS: 59 English-speaking women aged 70 years and older with no prior history of breast cancer. RESULTS: Very few women were familiar with the concept of overdetection and overtreatment. After the scenarios were presented, half of the women still demonstrated a lack of understanding of the concept of overdetection. Many women expressed suspicion of the concept, equating it to rationing. Women who showed understanding of overdetection were more likely to express an intent to discontinue screening, although 86% of the women stated that hearing about overdetection did not influence their screening decision. Themes identified did not differ by race/ethnicity, education, age or screening preferences. Differences were identified between women who understood overdetection and women who did not (r=0.23, p<0.001). CONCLUSIONS: Many older women did not understand the concept of overdetection, in addition to being suspicious of or resistant to the concept. Providing older women with descriptions of overdetection may not be sufficient to influence screening intentions.

Development and validation of a claims-based approach to proxy ECOG performance status across ten tumor groups.

AIM: To develop a claims-based prediction model of poor performance status (PS) in commercially insured and Medicare supplemental beneficiaries with cancer. PATIENTS & METHODS: Retrospective analysis was conducted of electronic medical records (EMR) from community oncology practices linked to MarketScan claims. Multivariable logistic regression predicted PS scores from the EMR using claims-based diagnostic and procedure codes. RESULTS: The study included 8442 patients diagnosed with cancer from 2007 to 2015. Overall, 8.1% of patients had poor EMR-based PS. Bootstrapping results from the final model showed sensitivity and specificity of approximately 75% with a predicted probability cutpoint = 0.078, c-statistic = 0.821 and pseudo-R2 = 0.25. CONCLUSION: Patients with poor PS can be identified in claims data. This prediction model enables future studies evaluating cancer treatments and outcomes to account for PS.

Minimization of olaratumab drug waste using real-world data.

PURPOSE: Results of a study in which population-based body weight and body surface area (BSA) data were used for vial size optimization to reduce drug waste associated with administration of the i.v. anticancer agent olaratumab are reported. METHODS: A retrospective observational study was conducted to determine weight and BSA distributions in a large sample of U.S. oncology patients using data from a large electronic medical record database. Body weight and BSA values at the time of initial systemic anticancer therapy were used to compute olaratumab dose requirements in a cohort of patients with soft tissue sarcoma; those data were analyzed to derive estimates of drug waste likely to result from the use of various proposed olaratumab vial sizes in combination with an existing 500-mg size. Weight and BSA distributions were calculated for additional cohorts of patients with 7 other cancer types. RESULTS: Median weight values in men (n = 1,179) and women (n = 1,078) with soft tissue sarcoma were 82.55 kg (interquartile range [IQR], 72.58-95.53 kg) and 68.69 kg (IQR, 58.51-84.28 kg), respectively. Modeling of olaratumab dosing scenarios indicated that use of the 500-mg vial only would result in estimated average drug waste of 234 mg per patient per administration; analysis of various potential vial size combinations showed that waste could be reduced by 87.6% with the addition of a 190-mg vial size. CONCLUSION: Analysis of real-world patient weight and BSA data allowed olaratumab vial size optimization to enable maximal dosing flexibility with minimal drug waste.