Real-world patient characteristics and treatment patterns in US patients with advanced non-small cell lung cancer.

BACKGROUND: Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to describe the real-world patient characteristics and treatment patterns of first-line treatment in patients in the US with NSCLC. METHODS: This was an observational, retrospective cohort study based on electronic medical records of US adults with locally advanced or metastatic disease in the ConcertAI Patient360 NSCLC database who initiated first-line treatment with anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy between July 2016 and December 2020. The analysis used patient attributes, clinical characteristics, and treatments from each patient's medical records. RESULTS: A total of 2175 patients were eligible for analysis. The median age was 68 years, and 26.2% of the patients were ≥75 years old. At treatment initiation, 96.4% and 3.6% of the patients had Stage 4 and Stage 3 (B or C) NSCLC, respectively. The most common histology type was nonsquamous adenocarcinoma (66.4%), and 19.8% had Eastern Cooperative Oncology Group performance status ≥2. Immunosuppressive medications were being used by 17.7% of patients, and 11.0% were immunocompromised. Almost all patients had metastases: 64.6% had 1, 23.2% had 2, and 8.0% had ≥3 metastatic sites. Brain metastases were present in 22.9% of patients. Treatment evolution was observed with first-line standard of care shifting from single-agent immunotherapy in 2016 (90.2%) to combination immunotherapy and chemotherapy in 2020 (60.2%). CONCLUSION: Between 2016 and 2020, the first-line treatment paradigm for advanced NSCLC in the US shifted from anti-PD-1/PD-L1 monotherapy to combination chemoimmunotherapy, with increasing biomarker testing. Further research in heterogeneous patient populations to characterize treatment strategies is warranted.

Real-world treatment patterns and outcomes of patients with metastatic nonsquamous non-small cell lung cancer after progression on standard-of-care therapy in the United States.

OBJECTIVES: Data to guide treatment selection in metastatic nonsquamous (mNSq) non-small cell lung cancer (NSCLC) after progression on current standard-of-care (SoC) treatment are limited. We investigated patterns of treatment and clinical outcomes following one or more disease progressions on SoC. MATERIALS AND METHODS: Electronic medical records in the ConcertAI Patient360 NSCLC database were analyzed for US adults with mNSq NSCLC who initiated treatment between 2016 and 2021. Analyses were conducted separately for patients who had ≥1 prior lines of therapy and progression(s) without (Cohort 1) or with (Cohort 2) evidence of targetable genetic alterations (EGFR, ALK, or ROS1). Outcomes included real-world progression-free survival (rwPFS) and overall survival (rwOS). RESULTS: Cohorts 1 and 2 included 281 and 109 patients, respectively. In Cohort 1, subsequent treatment was most often with docetaxel monotherapy (18.5%) or docetaxel + ramucirumab (32.4%). Most patients in Cohort 2 received platinum-based doublet chemotherapy with (22.9%) or without (34.9%) immunotherapy. Median rwPFS and rwOS were 2.9 and 7.2 months, respectively, in Cohort 1, and 3.2 and 10.4 months in Cohort 2. Neither the addition of ramucirumab to docetaxel in Cohort 1 nor the addition of immunotherapy to chemotherapy in Cohort 2 was associated with a marked improvement in additional survival. CONCLUSION: Patients with progressive mNSq NSCLC most commonly received later-line docetaxel for cancer without driver mutations, or platinum-based chemotherapy (following one or more lines of tyrosine kinase inhibitor therapy) for cancer with driver mutations, consistent with guideline recommendations. Median survival was poor regardless of subsequent treatment, highlighting the need for more effective options.

Assessing the Impact of CALGB 9343 on Surgical Trends in Elderly-Women With Stage I ER+ Breast Cancer: A SEER-Based Analysis.

Purpose: Lumpectomy (L) and breast radiotherapy (RT) results in equivalent outcomes in comparison to mastectomy (M) for early-stage breast cancer (BC) based on randomized controlled trials (RCT). Since 2004, RCT support that L without RT yields equivalent survival and acceptable local-regional outcomes in women ≥70-years old with T1N0 hormone-sensitive (ER+) BC on endocrine therapy. Based on this, we hypothesized that M rates should decrease substantially after 2004 in this low-risk elderly population. Methods: We used the Surveillance Epidemiology and End Results registry data to conduct this study. We included women with T1N0 ER+ BC from 2000 to 2014. We compared M rates in women diagnosed from 2000 to 2004 vs. 2005-2012 using the Chi-Square test. Logistic regression analyses was performed to examine demographic/clinical factors associated with mastectomy. Results: 67,506 women met the study criteria. In elderly Stage I ER+ BC, the M rate decreased by 6.3%: 29.0% before 2004 to 22.7% after 2004 (p < 0.0001). M rates remained higher in elderly non-Hispanic black (NHB, 27.1%, p < 0.0001), non-Hispanic Asian-Pacific-Islander (NHAPI, 30.1%, p < 0.0001), and Hispanics (24.4%, p = 0.0004) vs. non-Hispanic White (NHW, 21.5%). Treatment in the modern cohort was associated with decreased odds of mastectomy (OR = 0.71, 95% CI 0.68-0.74, p < 0.0001) while NH-API race was associated with the highest increased odds of mastectomy (OR = 1.65, 95% 1.53-1.78, p < 0.0001). In the modern cohort specifically (2005-2014), Hispanic women (OR = 1.12, p = 0.014), NHB women (OR = 1.21, p < 0.0001), and NHAPI women (OR = 1.73, p < 0.0001) all had higher odds of undergoing mastectomy relative to NHW women after adjusting for all other patient and tumor related factors. Conclusions: In elderly patients with stage I, ER+ BC, M rates have decreased modestly since 2004. These trends are driven mostly be decreases in the M rate in NHW women, but M rates remain ~25% in Hispanic, NHB, and NHAPI women. Further research is needed to identify why M, which is associated with higher cost and morbidity than L alone, has not changed substantially in elderly, low-risk BC.

Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With Second-Line Therapies for Medicare Patients With Advanced Non-Small-Cell Lung Cancer.

INTRODUCTION: Real-world data on current treatment practices for non-small-cell lung cancer (NSCLC) are needed to understand the place in therapy and potential economic impact of newer therapies. PATIENTS AND METHODS: This retrospective cohort study identified patients ≥ 65 years old in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database with first-time diagnosis of stage IIIB/IV NSCLC from 2007-2011 who received second-line therapy after first-line platinum-based chemotherapy from 2007 through mid-2013. Second-line regimens, health care resource use, adverse events (AEs), and associated costs were analyzed descriptively. Overall survival was determined by Kaplan-Meier test. Costs were adjusted to 2013 US dollars. RESULTS: We identified 4033 patients with advanced NSCLC who received second-line therapy (47% of those who received first-line platinum-based chemotherapy). Mean (SD) age was 73 (5) years, 2246 (56%) were male; 1134 (28%) and 2899 (72%) had squamous and nonsquamous NSCLC, respectively. The 4 most common second-line regimens were pemetrexed (22%), docetaxel (12%), carboplatin/paclitaxel (11%), and gemcitabine (7%). Median overall survival from second-line therapy initiation was 7.3 months (95% confidence interval, 7.0-7.7). Dyspnea and anemia were the most common AEs of interest, affecting 29% and 26% of patients, respectively; atypical pneumonia was associated with the highest AE-related costs (mean, $5339). The mean total per-patient-per-month cost was $10,885; AE-related per-patient-per-month costs totaled $1036 (10%). Costs were highest for pemetrexed-treated patients. CONCLUSION: These real-world data illustrate the variety of second-line regimens, poor prognosis, and high cost of second-line chemotherapy for patients with advanced NSCLC treated before the approval of immunotherapies for these patients.

C-reactive protein concentration and risk of selected obesity-related cancers in the Women's Health Initiative.

BACKGROUND: Obesity is a chronic inflammatory condition strongly associated with the risk of numerous cancers. We examined the association between circulating high-sensitivity C-reactive protein (hsCRP), a biomarker of inflammation and strong correlate of obesity, and the risk of three understudied obesity-related cancers in postmenopausal women: ovarian cancer, kidney cancer, and multiple myeloma. METHODS: Participants were 24,205 postmenopausal women who had measurements of baseline serum hsCRP (mg/L) in the Women's Health Initiative (WHI) CVD Biomarkers Cohort, a collection of four sub-studies within the WHI. Incident cancers were identified over 17.9 years of follow-up (n = 153 ovarian, n = 110 kidney, n = 137 multiple myeloma). hsCRP was categorized into study-specific quartiles. Adjusted Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of baseline hsCRP with the risk of these cancers. RESULTS: There was no clear association between baseline hsCRP concentration and the risk of ovarian cancer (quartile 4 vs. 1: HR 0.87, 95% CI 0.56-1.37), kidney cancer (HR 0.95, 95% CI 0.56-1.61), or multiple myeloma (HR 0.82, 95% CI 0.52-1.29). HRs for 1 mg/L increases in hsCRP also approximated the null value for each cancer. CONCLUSIONS: The results of this study suggest that elevated CRP is not a major risk factor for these obesity-related cancers (ovarian or kidney cancers, or multiple myeloma) among postmenopausal women. Given the importance of elucidating the mechanisms underlying the association of obesity with cancer risk, further analysis with expanded biomarkers and in larger or pooled prospective cohorts is warranted.

Real-World Treatment Patterns, Overall Survival, and Occurrence and Costs of Adverse Events Associated With First-line Therapies for Medicare Patients 65 Years and Older With Advanced Non-small-cell Lung Cancer: A Retrospective Study.

PURPOSE: This study sought to better understand real-world treatment patterns, overall and non-small-cell lung cancer (NSCLC)-specific survival, adverse event (AE) occurrence, and economic impact of first-line cancer therapies in Medicare patients. PATIENTS AND METHODS: This retrospective cohort study identified patients ≥ 65 years in the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database who received a first-time advanced (stage IV) NSCLC diagnosis from 2007 to 2011, and who received first-line platinum-based chemotherapy from 2007 through mid-2013. First-line regimens, healthcare resource use, occurrence of AEs, and associated costs (2013 US dollars) were analyzed. Median survival was determined using the Kaplan-Meier method. RESULTS: Surprisingly, only 46% of patients (n = 13,472) with stage IIIB/IV NSCLC received systemic therapy, and 5931 received platinum-based therapy. The mean age was 73 years, with 3354 (57%) males; 1489 (25%) had squamous and 4442 (75%) nonsquamous histology. The most common regimens were carboplatin doublets (70%), including carboplatin/paclitaxel (38%), carboplatin/pemetrexed (12%), carboplatin/gemcitabine (11%), and carboplatin/docetaxel (7%). The median overall survival from first-line therapy initiation was 7.2 months (95% confidence interval, 7.0-7.5 months). Dyspnea and anemia were the most common AEs of interest, whereas atypical pneumonia was associated with the greatest AE-related costs (mean, $5044). The mean total per-patient-per-month cost was $11,909, with AE-related costs comprising 9% of total costs. The highest costs and survival were observed for patients treated with carboplatin/pemetrexed and bevacizumab/carboplatin/paclitaxel. CONCLUSIONS: These real-world data illustrate the most common first-line regimens by histology, overall survival, AEs, and some of the high AE-related costs of therapy for advanced NSCLC, and provides extremely useful information for clinicians.

Ibuprofen and fatal lung cancer: A brief report of the prospective results from the Third National Health and Nutrition Examination Survey (NHANES III).

Chronic inflammation appears to increase the risk of lung cancer and, reciprocally, agents that reduce inflammation have been found to reduce this risk. However, few prospective studies have assessed whether there exists an association between lung cancer and the use of non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, the association between fatal lung cancer and NSAIDs was investigated using cohort data from the Third National Health and Nutrition Examination Study (NHANES III). Baseline data were collected on smoking, NSAID use and other lifestyle factors for 10,735 participants during 1988-1994, with cause-specific mortality status ascertained through probabilistic record matching based on the National Death Index until 2006. Cox proportional hazards regression models were conducted to estimate hazard ratios (HRs) and confidence intervals (CIs) for NSAID use and death from lung cancer, controlling for current smoking and other covariates. During the 18 years of follow-up, 269 participants succumbed to lung cancer, of whom 252 (93.6%) reported a history of cigarette smoking. Since all but 17 of the 269 fatal lung cancer cases occurred among current or former smokers, estimates of NSAID effects were ascertained from a sub-cohort of 5,882 individuals who reported a history of past or current cigarette smoking. Multivariate regression models revealed that regular use of ibuprofen resulted in a 48% reduced risk of lung cancer mortality (HR=0.52, 95% CI: 0.33-0.82, P<0.01). The main effects of other compounds tested, such as aspirin or acetaminophen, were not statistically significant. Our results suggest that high-risk subgroups of smokers may benefit from the regular use of specific NSAIDs, which may prove to be a useful strategy for lung cancer prevention.

Costs of Diagnostic Assessment for Lung Cancer: A Medicare Claims Analysis.

PURPOSE: To assess the diagnostic costs leading up to a lung cancer diagnosis in patients with abnormal computed tomography (CT) scans. PATIENTS AND METHODS: A retrospective cohort study using the 5% Medicare claims data (January 1, 2009, to December 31, 2011) was conducted. Patients aged 65 to 74 years with an abnormal chest CT scan were identified. Index was defined as the date of the abnormal chest CT scan. Outcomes assessed over a 12-month follow-up after index included lung cancer diagnosis rate and the use and associated costs of follow-up diagnostic tests up to diagnosis of lung cancer. RESULTS: Of 8979 patients identified with an abnormal chest CT scan (mean age, 69.3 ± 2.9 years), 13.9% were diagnosed with lung cancer over 12 months. Chest x-rays were the most common diagnostic test. Of the 19% who underwent a biopsy, 43.6% were not diagnosed with lung cancer during follow-up. The average total diagnostic assessment cost per patient was higher for those with versus without lung cancer ($7567 vs. $3558). Among patients not diagnosed with lung cancer, the median diagnostic cost per patient for those with versus without biopsy was ∼ 28 times higher. Adverse events significantly increased the average cost per biopsy (approximately 4-fold). CONCLUSION: Total lung cancer diagnostic cost was $38.3M in the defined study sample, of which 43.1% was accounted for by biopsied patients without a lung cancer diagnosis. Additional risk stratification is required to decrease unnecessary biopsy referrals and costs. Further, adverse events significantly increased costs.

Lack of private health insurance is associated with higher mortality from cancer and other chronic diseases, poor diet quality, and inflammatory biomarkers in the United States.

OBJECTIVE: The lack of health insurance reduces access to care and often results in poorer health outcomes. The present study simultaneously assessed the effects of health insurance on cancer and chronic disease mortality, as well as the inter-relationships with diet, obesity, smoking, and inflammatory biomarkers. We hypothesized that public/no insurance versus private insurance would result in increased cancer/chronic disease mortality due to the increased prevalence of inflammation-related lifestyle factors in the underinsured population. METHODS: Data from the Third National Health and Nutrition Examination Survey participants (NHANES III;1988-1994) were prospectively examined to assess the effects of public/no insurance versus private insurance and inflammation-related lifestyle factors on mortality risk from cancer, all causes, cardiovascular disease (CVD) and diabetes. Cox proportional hazards regression was performed to assess these relationships. RESULTS: Multivariate regression analyses revealed substantially greater risks of mortality ranging from 35% to 245% for public/no insurance versus private insurance for cancer (HR=1.35; 95% CI=1.09,1.66), all causes (HR=1.54; 95% CI=1.39,1.70), CVD (HR=1.62; 95% CI=1.38,1.90) and diabetes (HR=2.45; 95% CI=1.45,4.14). Elevated CRP, smoking, reduced diet quality and higher BMI were more prevalent in those with public insurance, and were also associated with increased risks of cancer/chronic disease mortality. DISCUSSION: Insurance status was strongly associated with cancer/chronic disease mortality after adjusting for lifestyle factors. The results suggest that inadequate health insurance coverage results in a substantially greater need for preventive strategies that focus on tobacco control, obesity, and improved dietary quality. These efforts should be incorporated into comprehensive insurance coverage programs for all Americans.

Prospective evaluation of C-reactive protein, smoking and lung cancer death in the Third National Health and Nutrition Examination Survey.

Chronic inflammation plays an important role in lung carcinogenesis. Few prospective studies have examined associations between lung cancer, serum C-reactive protein (CRP), a measure of systemic inflammation, and inflammatory lifestyle factors, such as smoking and obesity. This study prospectively examined the relationship between CRP and lung cancer death and its interrelationships with several lifestyle factors. Baseline data on smoking and other lifestyle variables were collected for 8,950 participants in the Third National Health and Nutrition Examination Survey (NHANES III: 1988-1994). Baseline CRP levels were measured in serum samples by nephelometry. Mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) for CRP and lung cancer death, with adjustment for smoking and other variables. During 18 years of follow-up, 219 individuals died from lung cancer. Multivariate regression models revealed a dose-response effect for elevated CRP and risk of lung cancer death when adjusting for age, gender, BMI and smoking. Compared to individuals with CRP <3 mg/l, lung cancer death was significantly associated with elevated levels of CRP: HR=1.63 (95% CI=1.15-2.26) for 3-7 mg/l and HR=2.44 (95% CI=1.81­3.45) for CRP >7 mg/l, P-trend <0.0001). The risk of lung cancer death for smokers increased 9-fold in adjusted models (P<0.0001). When stratified by gender and smoking status the effects of CRP were similar for smokers and males but did not reach statistical significance for females and non-smokers. This study supports a dose-dependent relationship between lung cancer death and CRP for males and smokers, but additional efforts are needed to better elucidate these relationships in women and non-smokers. The results suggest that CRP may emerge as a valuable tool in identifying high-risk subgroups of smokers for lung cancer prevention strategies.

Assessment of the effects of severe obesity and lifestyle risk factors on stage of endometrial cancer.

BACKGROUND: Lifestyle risk factors, including obesity, have been associated with increased risk of endometrial cancer (EC). Women with higher obesity levels tend to have less aggressive EC disease stage and histology. This study further investigated associations between nonmodifiable risk factors, such as age, race, and grade, and modifiable lifestyle factors, such as diet and physical activity expenditure, in relation to severe obesity and late versus early EC stage at diagnosis. METHODS: Demographic, anthropometric, and lifestyle surveys were administered to 177 women with histologically confirmed EC. Logistic regression analyses assessed the relationship between obesity and other risk factors on EC stage at diagnosis. RESULTS: In multivariate models, body mass index (BMI) < 35 was not significantly associated with late EC stage at diagnosis (OR = 1.67, P = 0.219) when adjusting for grade and age. Grade was significantly associated with EC stage when controlling for BMI and age (OR = 8.48, P = .000). Women more than the age of 60 had a fourfold increased risk of diagnosis at late versus early EC stage when adjusting for other risk factors. Age had a confounding effect on the obesity-EC stage association. CONCLUSIONS: Our results corroborate those of past studies showing that BMI is not an independent risk factor for EC stage and that age may have confounded the obesity-EC stage association. Because of mixed results and implications for treatment outcomes, however, further research examining these variables is warranted. IMPACT: Our results provide further insight into the obesity EC-stage association, especially the confounding effect of age. Future studies should examine modifiable lifestyle factors in larger and more diverse populations.

Exercise and dietary change after diagnosis and cancer-related symptoms in long-term survivors of breast cancer: CALGB 79804.

OBJECTIVE: Improving diet and exercise can reduce survivors' risk of cancer-related fatigue, poor physical functioning, and potential recurrence. A cancer diagnosis can represent a 'teachable moment', leading survivors to make positive changes in diet and exercise behaviors; however, little is known about how often this occurs or about factors that enhance or limit survivors' ability to make these changes. This cross-sectional descriptive study investigated both the prevalence and clustering of self-reported changes in diet and exercise and how these changes related to ongoing cancer-related symptoms, social support, and stressful life events among long-term breast cancer survivors. METHODS: Survivors (n=227, response rate=72%) of a prior Cancer and Leukemia Group B treatment trial, on average 12 years post-diagnosis, completed a mailed survey assessing health behavior changes since diagnosis and current symptoms, social support, and stressful life events. RESULTS: Over half of survivors reported making positive exercise or diet changes since diagnosis: over 25% reported making exercise and diet changes. Analyses of covariance models showed that survivors who reported increasing their exercise also reported lower fatigue. Trends were also found between increased fruit and vegetable intake and decreased fatigue and between increased exercise and increased social support. CONCLUSIONS: These results underscore the need for health promotion efforts among survivors. Exercise promotion is especially needed since more survivors attempted to change dietary behaviors than exercise on their own. Further, fatigue may limit survivors' ability to change their health behaviors; alternatively, survivors who increase their exercise may experience less fatigue.

Arm/hand swelling and perceived functioning among breast cancer survivors 12 years post-diagnosis: CALGB 79804.

INTRODUCTION: Lymphedema is an under-reported and debilitating consequence of axillary node dissection among breast cancer survivors. This study describes the characteristics of arm and hand swelling in relation to perceived physical and mental health functioning among breast cancer survivors 9-16 years post-diagnosis who previously participated in a clinical trial coordinated by the Cancer and Leukemia Group B (CALGB 8541). METHODS: Eligible survivors of CALGB 8541 completed questionnaires assessing demographics, arm/hand swelling, perceived physical functioning, and mental health. RESULTS: Two hundred forty-five women (94% white, mean age = 63, on average 12.4 years post-diagnosis) completed questionnaires (participation rate = 78%). Seventy-five women (31%) reported arm/hand swelling since their surgery. Of these women, 76% reported current swelling and half reported constant swelling, mainly in the upper arm. Swelling was reported as mild or moderate in 88% of the women. Women who reported severe swelling had significantly worse physical functioning and trended toward worse depressive symptoms and poorer mental health (lower mental SF-36 scores) as well. Activity-limiting swelling was also significantly associated with worse physical functioning. Although swelling interfered with wearing clothing (36%) and perceptions about general appearance (32%), only 37% of women sought treatment for swelling. CONCLUSIONS: Arm/hand swelling is a chronic problem for a subgroup of long-term survivors of breast cancer, negatively affecting physical functioning. IMPLICATIONS FOR CANCER SURVIVORS: Educational efforts are needed as part of a comprehensive survivorship care plan to raise awareness about lymphedema so that survivors may identify this complication, seek treatment early, and potentially improve their physical functioning.

Applying a conceptual model for examining health-related quality of life in long-term breast cancer survivors: CALGB study 79804.

OBJECTIVES: The Survivor's Health and Reaction study used a quality-of-life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health-related quality of life (HRQL) and to document the prevalence of problems and health-oriented behaviors in a follow-up study of breast cancer patients who participated in CALGB 8541. METHODS: A total of 245 survivors (78% of those invited) who were 9.4-16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. RESULTS: The regression model revealed that decreased energy levels (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR=2.39, 95% CI: 1.10, 5.19), and lower social support (OR=1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). CONCLUSION: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors.