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Shortness of breath is a distressing symptom that occurs in 10% to 70% of oncology patients. Despite this broad range in its occurrence, little is known about inter-individual variability in shortness of breath and associated risk factors among patients receiving chemotherapy.Identify subgroups of patients with distinct shortness of breath profiles; evaluate for differences among these subgroups in demographic and clinical characteristics; evaluate for differences among symptom dimensions of shortness of breath, and evaluate for differences in quality of life outcomes.Outpatients (n=1338) completed questionnaires six times over two chemotherapy cycles. Occurrence of shortness of breath was assessed using the Memorial Symptom Assessment Scale. Latent class analysis was used to identify subgroups of patients with distinct shortness of breath profiles.Four distinct shortness of breath profiles were identified (None [70.5%], Decreasing [8.2%], Increasing [7.8%], High [13.5%]). Risk factors for membership in High class included: history of smoking, self-reported diagnosis of lung disease, having lung cancer, and receipt of a higher number of cancer treatments. Compared to the None class, High class reported poorer physical, psychological, and social functioning.Almost 14% of patients with heterogeneous types of cancer receiving chemotherapy had persistently high occurrence rates of shortness of breath for almost two months. In addition, compared to the Decreasing and Increasing classes, the High class' episodes of shortness of breath were more frequent and more severe. Clinicians need to assess all oncology patients for shortness of breath and provide targeted interventions.

Older patients with poor prognosis cancers have complex needs that can benefit from geriatrics and palliative care principles. Because they are not routinely assessed, the prevalence of preexisting geriatric and palliative conditions in this population is unknown.We used the nationally representative Health and Retirement Study (HRS) linked with Medicare claims (1998-2016) to identify adults aged ≥65 years diagnosed with poor prognosis cancers (cancers with a median survival ≤1 year). Using the HRS interview before the first Medicare cancer claim, we used survey-weighted descriptive statistics and modified Poisson regression analysis to examine the prevalence of the following clinically significant conditions: functional impairment, difficulty with mobility, falls and injurious falls, social support, cognition, advance care planning, use of pain or sleep medications, and presence of pain or breathlessness.Of 2105 participants (mean age 76, 53% women, 34% lung cancer, 21% gastrointestinal cancer), the median survival was 9.6 months. Approximately 65% had difficulty climbing stairs (95% CI 63%-67%), 49% had no advance directive (95% CI 45%-54%), 35% lived alone (95% CI 33%-37%), 36% fell in the last 2 years (95% CI 34%-38%), and 32% rated their memory as poor (95% CI 29%-34%). After adjusting for gender, cancer type, and HRS survey time before the first Medicare claim for a poor prognosis cancer, functional impairment and falls were highest among adults aged 85+. Adults aged 65-74 years were less likely to have an advance directive. After adjusting for age, cancer type, and HRS survey time, women had a higher rate of pain and physical impairment. In exploratory analyses, race and socioeconomic status predicted difficulty with mobility and instrumental activities of daily living, living alone, and advance directive completion.Due to a high prevalence across multiple domains, all older adults with poor prognosis cancers should be assessed for geriatric and palliative care conditions.

An academic career in aging research is filled with the incredible highs of important discoveries that improve the lives of older adults and repeated lows when papers and grants are rejected or studies are negative. To normalize the experience of setbacks and failures in aging research, we invited three senior investigators to share their journeys of persistence and resilience as they have navigated their research careers. This career development symposium was presented at the 2021 Annual Scientific Meeting of the American Geriatrics Society, which was held virtually. We aimed to connect researchers in aging, especially trainees and junior investigators, through personal stories of persistence and shared strategies to build resilience and respond to setbacks with a growth mindset.

IntroductionEGFR mutations drive a subset of NSCLC. Patients harboring the common EGFR mutations, deletion ofexon 19 and L858R, respond well to osimertinib, a third-generation tyrosine kinase inhibitor. Nevertheless, the effect of osimertinib on NSCLC with atypical EGFR mutations is not well described. This multicenter retrospective study evaluates the efficacy of osimertinib among patients with NSCLC harboring atypical EGFR mutations.MethodsPatients with metastatic NSCLC treated with osimertinib, harboring at least one atypical EGFR mutation, excluding concurrent deletion of exon 19, L858R, or T790M mutations, from six U.S. academic cancer centers were included. Baseline clinical characteristics were collected. The primary end point was the time to treatment discontinuation (TTD) of osimertinib. Objective response rate by the Response Evaluation Criteria in Solid Tumors version 1.1 was also assessed.ResultsA total of 50 patients with NSCLC with uncommon EGFR mutations were identified. The most frequent EGFR mutations were L861Q (40%, n= 18), G719X (28%, n= 14), and exon 20 insertion (14%, n= 7). The median TTD of osimertinib was 9.7 months (95% confidence interval [CI]: 6.5-12.9 mo) overall and 10.7 months (95% CI: 3.2-18.1 mo) in the first-line setting (n= 20). The objective response rate was 31.7% (95% CI: 18.1%-48.1%) overall and 41.2% (95% CI: 18.4%-67.1%) in the first-line setting. The median TTD varied among patients with L861Q (17.2 mo), G719X (7.8 mo), and exon 20 insertion (1.5 mo) mutations.ConclusionsOsimertinib has activity in patients with NSCLC harboring atypical EGFR mutations. Osimertinib activity differs by the type of atypical EGFR-activating mutation.

Cancer survival has improved since the 1990s, but to different extents across age groups, with a disadvantage for older adults. We aimed to quantify age-related differences in relative survival (RS - one-year, and one-year conditioning on surviving one year) for 10 common cancer types by stage at diagnosis. We used data from 18 United States Surveillance Epidemiology and End Results cancer registries and included cancers diagnosed between 2012-2016 followed until December 31, 2017. We estimated absolute differences in RS between the 50-64 age group and the 75-84 age group. The smallest differences were observed for prostate and breast cancers (1.8%-points [95% confidence interval (CI):1.5-2.1] and 1.9%-points [95%CI:1.5-2.3], respectively). The largest was for ovarian cancer (27%-points, 95%CI:24-29). For other cancers, differences ranged between 7 (95%CI:5-9, esophagus) and 18%-points (95%CI: 17-19, pancreas). Except for pancreatic cancer, cancer type and stage combinations with very high (>95%) or very low (Novelty and ImpactIn this analysis of United States population-based cancer registry data, age-related differences in cancer survival varied widely, ranging from less than 1% absolute difference in localized breast and prostate cancer survival to over 30% absolute difference in localized pancreatic cancer survival. Focused efforts to reduce age-related differences in cancer survival may have greatest impact by prioritizing cancer site and stage combinations with the widest differences.

PURPOSE: To determine patient and disease characteristics associated with functional disability among adults with advanced non–small-cell lung cancer (NSCLC). METHODS: In a prospective cohort of participants newly diagnosed with advanced NSCLC and beginning systemic treatment, functional disability in usual activities, mobility, and self-care was measured using the EuroQol-5D-5L at baseline. Demographics, comorbidities, brain metastases, Eastern Cooperative Oncology Group performance status (ECOG PS), and psychologic variables (depression [Patient Health Questionnaire-9] and anxiety [Generalized Anxiety Disorder 7-item scale]) were captured. Patients were classified into two disability groups (none-slight or moderate-severe) on the basis of total functional status scores. Differences between disability groups were determined (chi-square and t tests). Associations between patient characteristics and baseline disability were assessed using logistic regression. RESULTS: Among 173 participants, mean age was 63.3 years, 56% were male, 83% had ECOG PS 0-1, and 41% had brain metastases. Baseline disability was present in 39% of participants, with patients having moderate to severe disability in usual activities (37.6%), mobility (26.6%), and self-care (5.2%). Depressive and/or anxiety symptoms ranged from none to severe (Patient Health Questionnaire 9-item scale M = 6.5, SD = 5.3). Depressive symptoms were the only characteristic associated with a higher odds of baseline disability (adjusted odds ratio [aOR]: 1.26; 95% CI, 1.15 to 1.38; P < .001). Participants with poorer ECOG PS (aOR: 4.64; 95% CI, 1.84 to 11.68; P = .001) and depressive symptoms (aOR: 1.15; 95% CI, 1.07 to 1.24; P < .001) had higher odds of moderate-severe mobility disability compared with the none-slight disability group. CONCLUSION: More than one third of all adults with advanced NSCLC have moderate-severe functional disability at baseline. Psychologic symptoms were significantly associated with moderate-severe baseline disability.

Functional outcomes during non-small cell lung cancer (NSCLC) treatment are critically important to older adults. Yet, data on physical function and which measures best capture functional change remain limited.This multisite, mixed methods cohort study recruited adults ≥65 years with advanced NSCLC starting systemic treatment (i.e., chemotherapy, immunotherapy, and/or targeted therapy) with non-curative intent. Participants underwent serial geriatric assessments prior to starting treatment and at one, two, four, and six months, which included the Karnofsky Performance Scale (KPS, range: 0-100%), instrumental activities of daily living (IADL, range: 0-14), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Physical Functioning subscale (EORTC QLQ-C30 PF, range: 0-100), and Life-Space Assessment (LSA, range: 0-120). For all measures, higher scores represent better functioning. In a qualitative substudy, 20 patients completed semi-structured interviews prior to starting treatment and at two and six months to explore how treatment affected their daily functioning. We created joint displays for each interview participant that integrated their longitudinal KPS, IADL, EORTC QLQ-C30 PF, and LSA scores with patient quotes describing their function.Among 87 patients, median age was 73 years (range 65-96). Mean pretreatment KPS score was 79% (standard deviation [SD] 13), EORTC QLQ-C30 PF was 69 (SD 23), and LSA was 67 (SD 28); median IADL was 13 (interquartile range [IQR] 10-14). At two months after treatment initiation, 70% of patients experienced functional decline on at least one measure, with only 13% of these patients recovering at six months. At two and six months, decline in LSA was the most common (48% and 35%, respectively). Joint displays revealed heterogeneity in how well each quantitative measure of physical function captured the qualitative patient experience.Functional decline during NSCLC treatment is common among older adults. LSA is a useful measure to detect subtle functional decline that may be missed by other measures. Given heterogeneity in how well each quantitative measure captures changes in physical function, there is value to including more than one functional measure in geriatric oncology research studies.

To improve the care of older adults with cancer, the traditional approach to clinical trial design needs to be reconsidered. Older adults are underrepresented in clinical trials with limited or no information on geriatric-specific factors, such as cognition or comorbidities. To address this knowledge gap and increase relevance of therapeutic clinical trial results to the real-life population, integration of aspects relevant to older adults is needed in oncology clinical trials. Geriatric assessment (GA) is a multidimensional tool comprising validated measures assessing specific health domains that are more frequently affected in older adults, including aspects related to physical function, comorbidity, medication use (polypharmacy), cognitive and psychological status, social support, and nutritional status. There are several mechanisms for incorporating either the full GA or specific GA measures into oncology therapeutic clinical trials to contribute to the overarching goal of the trial. Mechanisms include utilizing GA measures to better characterize the trial population, define trial eligibility, allocate treatment receipt within the context of the trial, develop predictive models for treatment outcomes, guide supportive care strategies, personalize care delivery, and assess longitudinal changes in GA domains. The objective of this manuscript is to review how GA measures can contribute to the overall goal of a clinical trial, to provide a framework to guide the selection and integration of GA measures into clinical trial design, and ultimately enable accrual of older adults to clinical trials by facilitating the design of trials tailored to older adults treated in clinical practice.

PURPOSE This Provisional Clinical Opinion update presents a clinically pragmatic approach to hepatitis B virus (HBV) screening and management. PROVISIONAL CLINICAL OPINION All patients anticipating systemic anticancer therapy should be tested for HBV by 3 tests—hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc) total immunoglobulin (Ig) or IgG, and antibody to hepatitis B surface antigen—but anticancer therapy should not be delayed. Findings of chronic HBV (HBsAg-positive) or past HBV (HBsAg-negative and anti-HBc–positive) infection require HBV reactivation risk assessment. Patients with chronic HBV receiving any systemic anticancer therapy should receive antiviral prophylactic therapy through and for minimum 12 months following anticancer therapy. Hormonal therapy alone should not pose a substantial risk of HBV reactivation in patients with chronic HBV receiving hormonal therapy alone; these patients may follow noncancer HBV monitoring and treatment guidance. Coordination of care with a clinician experienced in HBV management is recommended for patients with chronic HBV to determine HBV monitoring and long-term antiviral therapy after completion of anticancer therapy. Patients with past HBV infection undergoing anticancer therapies associated with a high risk of HBV reactivation, such as anti-CD20 monoclonal antibodies or stem-cell transplantation, should receive antiviral prophylaxis during and for minimum 12 months after anticancer therapy completion, with individualized management thereafter. Careful monitoring may be an alternative if patients and providers can adhere to frequent, consistent follow-up so antiviral therapy may begin at the earliest sign of reactivation. Patients with past HBV undergoing other systemic anticancer therapies not clearly associated with a high risk of HBV reactivation should be monitored with HBsAg and alanine aminotransferase during cancer treatment; antiviral therapy should commence if HBV reactivation occurs. Additional information is available at www.asco.org/supportive-care-guidelines .

Immunotherapy with checkpoint inhibitors against programmed cell death receptor (PD-1) and programmed cell death ligand (PD-L1) has been implemented in the treatment pathway of patients with non-small cell lung cancer (NSCLC) from locally advanced disease to the metastatic setting. This approach has resulted in improved survival and a more favourable toxicity profile when compared with chemotherapy. Following the successful introduction of single-agent immunotherapy, current clinical trials are focusing on combination treatments with chemotherapy or radiotherapy or even other immunotherapeutic agents. However, most of the data available from these trials are derived from, and therefore might be more applicable to younger and fitter patients rather than older and often frail lung cancer real-world patients. This article provides a detailed review of these immunotherapy agents with a focus on the data available regarding older NSCLC patients and makes recommendations to fill evidence gaps in this patient population.

BACKGROUND: Shared decision making (SDM) is especially important for older adults with cancer given the risks of over- and undertreatment, uncertainty regarding benefits/harms worsened by research underrepresentation, and individual preferences. We aimed to adapt the Best Case/Worst Case (BC/WC) communication tool, which improves SDM in geriatric surgery, to geriatric oncology. METHODS: We conducted focus groups with 40 stakeholders (fourteen older adults with lung cancer, twelve caregivers, fourteen medical oncologists) to elicit perspectives on using the BC/WC tool for geriatric oncology and to identify components needing refinement. During each focus group, participants viewed a BC/WC demonstration video and answered questions modified from the Decision Aid Acceptability Scale. We analyzed transcripts using deductive and inductive thematic analyses. DISCUSSION: Participants believed that the BC/WC tool could help patients understand their cancer care choices, explore tradeoffs and picture potential outcomes, and deliberate about decisions based on their goals, preferences, and values. Oncologists also reported the tool could guide conversations to address points that may frequently be skipped (e.g., alternative options, treatment goals). Participant preferences varied widely regarding discussion of the worst-case scenario and desire for statistical information. CONCLUSION: The BC/WC tool is a promising strategy that may improve SDM in geriatric oncology and patient understanding of alternative options and treatment goals. Based on participant input, adaptations will include framing cancer care as a series of decisions, eliciting patient preferences and asking permission before offering the worst-case scenario, and selection of the two most relevant options to present if multiple exist.

Dyspnea is a common and distressing symptom for oncology patients.However, dyspnea is not well-characterized and often underestimated by clinicians. This systematic review summarizes the prevalence, intensity, distress, and impact of dyspnea in oncology patients and identifies research gaps.A search of all of the relevant databases was done from 2009 to May 2022. A qualitative synthesis of the extant literature was performed using established guidelines.One hundred-seventeen studies met inclusion criteria. Weighted grand mean prevalence of dyspnea in patients with advanced cancer was 58.0%. Intensity of dyspnea was most common dimension evaluated, followed by the impact and distress. Depression and anxiety were the most common symptoms that co-occurred with dyspnea.Numerous methodologic challenges were evident across studies. Future studies need to use valid and reliable measures; evaluate the impact of dyspnea; and determine biomarkers for dyspnea.

BackgroundMaintenance of function during cancer treatment is important to older adults. Characteristics associated with pretreatment life-space mobility and changes during non-small cell lung cancer (NSCLC) treatment remain unknown.MethodsThis mixed methods cohort study recruited adults age ≥65 with advanced NSCLC starting palliative chemotherapy, immunotherapy, and/or targeted therapy from a Comprehensive Cancer Center, Veterans Affairs, and safety-net clinic. Patients completed geriatric assessments including Life-Space Assessment (LSA) pretreatment and at 1, 2, 4, and 6 months after treatment initiation. LSA scores range from 0 to 120 (greater mobility); LSA

ContextPatients with lung cancer who undergo chemotherapy (CTX) experience multiple symptoms. Evaluation of how these symptoms cluster together and how these symptom clusters change over time are salient questions in symptom clusters research.ObjectivesThe purposes of this analysis, in a sample of patients with lung cancer (n=145) who were receiving CTX, were to 1) evaluate for differences in the number and types of symptom clusters at three time points (i.e., before their next cycle of CTX, the week after CTX, and two weeks after CTX) using ratings of symptom occurrence and severity and 2) evaluate for changes in these symptom clusters over time.MethodsAt each assessment, a modified version of the Memorial Symptom Assessment Scale was used to assess the occurrence and severity of 38 symptoms. Exploratory factor analyses were used to extract the symptom clusters.ResultsAcross the two symptom dimensions (i.e., occurrence and severity) and the three assessments, six distinct symptom clusters were identified; however, only three of these clusters (i.e., lung cancer specific, psychological, nutritional) were relatively stable across both dimensions and across time. Two additional clusters varied by time but not by symptom dimension (i.e., epithelial/gastrointestinal and epithelial). A sickness behavior cluster was identified at each assessment with the exception of the week before CTX using only the severity dimension.ConclusionFindings provide insights into the most common symptom clusters in patients with lung cancer undergoing CTX. Most common symptoms within each cluster appear to be relatively stable across the two dimensions, as well as across time.

1538 Background: As more treatment options become available for advanced non-small cell lung cancer (NSCLC), oncologists still have difficulty predicting functional resiliency versus functional disability throughout treatment. Functional resiliency refers to the ability to recover baseline functional status in the face of an intervening health care event. This study aims to identify characteristics associated with resilience among adults with advanced NSCLC. Methods: In a prospective cohort of participants with newly diagnosed stage IV NSCLC, resilience was evaluated based on three functional disability items in the EQ-5D-5L (modified: mEQ-5D-5L) through 12 months of follow-up compared to baseline scores. This included patients treated with chemotherapy, immunotherapy, targeted agents and no treatment. Participants were classified into four groups: functional decline, maintenance, resilient, or variable. Resilience was determined based on improvement in disability scores, with a 1-point increase in functional status score representing a 0.5 standard deviation change on the mEQ-5D-5L. Patient characteristics included demographics, comorbidities, ECOG performance status, presence of brain or bone metastases, mood (GAD-7, PHQ-9), and lung cancer-specific symptoms (QLQ-LC13). Treatment toxicity and toxicity grades were also recorded. Differences between groups were determined through Fisher’s exact test or ANOVA. Results: Among 207 participants, 87 (42.0%) maintained functional status, 78 (37.7%) experienced functional decline, 22 (10.6%) were classified as resilient and 20 (9.7%) were variable. Characteristics associated with higher resilience (p < 0.1) included being employed (p = 0.02) and living in a metro setting (p = 0.10). Characteristics not associated with resilience included age, education level, smoking status, presence of brain metastases, ECOG performance status, or psychological symptoms. Approximately half the participants (n = 105, 50.7%) who received treatment experienced toxicities. One third (33.8%) experienced ≥ grade 3 toxicities. There was no significant association between toxicity grade and resilience grouping. Conclusions: Characteristics associated with functional resilience included employment status and living setting. At least half of adults with advanced NSCLC experience treatment-related toxicities. It is important to determine characteristics of resilience to better understand which patients will tolerate cancer treatments.

Background: Maintaining functional status is important to older adults with cancer, but data are limited on how systemic treatments affect functional status. We systematically reviewed changes in functional status during systemic cancer treatments and identified characteristics associated with functional decline and improvement. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Register of Controlled Trials for articles examining characteristics associated with functional changes in older adults during systemic cancer treatment published in English between database inception and January 11, 2019 (PROSPERO CRD42019123125). Findings were summarized with descriptive statistics. Study characteristics between older adult–specific and non–older adult–specific studies were compared using the Fisher exact test. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 44 studies, which enrolled >8,400 patients; 39% of studies focused on older adults (1 study enrolled adults aged ≥60 years, 10 enrolled adults aged ≥65 years, and 6 enrolled adults aged ≥70 years). Almost all studies (98%) used patient-reported outcomes to measure functional status; only 20% used physical performance tests. Reporting of functional change was heterogeneous, with 48% reporting change scores. Older adult–specific studies were more likely to analyze functional change dichotomously (29% vs 4%; P=.008). Functional decline ranged widely, from 6% to 90%. The most common patient characteristics associated with functional decline were older age (n=7 studies), worse performance status (n=4), progressive disease status (n=4), pain (n=4), anemia (n=4), and worse nutritional status (n=4). Twelve studies examined functional improvement and identified 11 unique associated characteristics. Conclusions: Functional decline is increasingly recognized as an important outcome in older adults with cancer, but definitions and analyses are heterogeneous, leading to a wide range of prevalence. To identify patients at highest risk of functional decline during systemic cancer treatments, trials need to routinely analyze functional outcomes and measure characteristics associated with decline (eg, nutrition).

Background Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes. Materials and Methods To compare fatigue and neuropathy longitudinally by age ( Results Older patients had on average a 0.17-point (95% confidence interval [CI], 0.00–0.34; p = .049) higher mean fatigue grade longitudinally compared with younger patients. PS 2 was associated with earlier development of grade ≥2 fatigue (hazard ratio [HR], 1.56; 95% CI, 1.07–2.27; p = .02). For neuropathy, older age was associated with earlier development of grade ≥2 neuropathy (HR, 1.41; 95% CI, 1.00–1.97; p = .049). Patients with PS 2 had a 1.30 point lower neuropathy AUC (95% CI, −2.36 to −0.25; p = .02) compared with PS 0–1. In contrast, maximum grade analyses only detected a higher percentage of older adults with grade ≥3 fatigue and neuropathy at some point during treatment. Conclusion Our comparison of complementary but distinct aspects of chemotherapy toxicity identified important longitudinal differences in fatigue and neuropathy by age and PS that are missed by the traditional maximum grade approach. Clinical trial identification number: NCT00003117 (CALGB 9730) Implications for Practice The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time. This toxicity over time analysis of fatigue and neuropathy during chemotherapy for advanced non-small cell lung cancer demonstrates how to use longitudinal methods to comprehensively characterize AEs over time by age and performance status (PS). We identified important longitudinal differences in fatigue and neuropathy that are missed by the maximum grade approach. This new information about how older adults and patients with PS 2 experience these toxicities longitudinally may be used clinically to improve discussions about treatment options and what to expect to inform shared decision making and symptom management.

Introduction Optimal treatment for older adults with stage III non-small cell lung cancer (NSCLC) remains unclear. Here we hypothesized that sequential chemoradiation therapy (sCRT) is better tolerated than concurrent (cCRT) but confers acceptable efficacy. We evaluated these strategies in older adults utilizing Alliance for Clinical Trials in Oncology data. Materials and methods Pooled analyses from 6 first-line stage III NSCLC CRT trials (Cancer and Leukemia Group B 8433, 8831, 9130, 30106, 30407, 39801) were used to compare toxicity and survival outcomes with cCRT versus sCRT in patients age ≥ 65 years. Grade 3–5 adverse events (AEs), progression-free and overall survival (PFS; OS) are reported with adjustment for covariates. Results Four hundred older adults, of whom 106 (26.5%) had received sCRT and 294 (73.5%) had received cCRT, comprised the cohorts. Virtually all had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0–1 (99%). More grade 3–5 AEs were observed at any time-point with cCRT than sCRT (94.2% versus 86.8%; 95% confidence interval for difference in proportions, 1.3%, 15.5%) and this finding remained after adjusting for length of study treatment (P = 0.018). Comparable PFS and OS were observed with sCRT versus cCRT (median: 8.0 versus 9.2 months; median: 11.9 versus 13.4 months, respectively) even after adjustment for age, sex, ECOG PS, body mass index, pretreatment weight loss, stage, and cisplatin-based therapy (P = 0.604 and P = 0.906, respectively). Discussion These data show that sCRT was associated with less toxicity than cCRT with no associated statistically significant decrease in efficacy outcomes and that sCRT merits further study in this population.

15 Background: Discordance in prognostic understanding between caregivers of adults with cancer and the patient’s oncologist is common. However, the relationship between caregiver-oncologist discordance and caregiver bereavement outcomes is unknown. We evaluated the associations of caregiver-oncologist discordance in beliefs about the patient’s curability and life expectancy with caregiver-reported therapeutic alliance and anxiety. Methods: This is a secondary analysis of a multicenter study that assessed the effect of a communication intervention among patients with advanced cancer and their caregivers. Prior to intervention exposure, caregivers and oncologists were asked about their belief in the patient’s chances for cure and living ≥2 years: 100%, about 90%, about 75%, about 50/50, about 25%, about 10%, and 0%. Discordance was defined as a difference by 2 response levels on each prognostic understanding item. Outcomes at 7 months after patient death included caregiver-reported therapeutic alliance [modified 5-item Human Connection (THC) scale] and anxiety (Generalized Anxiety Disorder-7). We used multivariable linear regression models to assess the independent associations of discordance with therapeutic alliance and anxiety. Results: We included 97 caregivers (mean age 63, range 22-83). Approximately 40% of caregiver-oncologist dyads had discordant beliefs about curability (caregivers were more optimistic in 100% of dyads) and 63% had discordant beliefs about life expectancy (caregivers were more optimistic in 94% of dyads). On multivariate analysis, discordance in beliefs about prognostic estimates was associated with lower THC score (b = -6.94, SE 3.17, p = 0.03). Discordance in beliefs about curability was associated with lower anxiety levels (b = -1.79, SE 0.90, p = 0.05). Conclusions: Caregiver-oncologist discordance may decrease caregiver-reported therapeutic alliance and anxiety, both of which may shape how caregivers interact with the healthcare system. A better understanding the role of caregivers’ prognostic understanding will guide interventions to improve caregiver-oncologist therapeutic alliance and caregiver anxiety. Clinical trial information: NCT01485627.

PURPOSE: While attentional function is an extremely important patient outcome for older adults, research on changes in function in this group is extremely limited. The purposes of this study were to: identify subgroups of older patients (i.e., latent growth classes) based on changes in their level of self-reported attentional function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality of life (QOL) outcomes. METHODS: Older oncology outpatients (n=365) who were assessed for changes in attention and working memory using the Attentional Function Index a total of six times over two cycles of chemotherapy (CTX). QOL was assessed using the Medical Outcomes Study-Short Form 12 and the QOL-Patient Version Scale. Latent profile analysis (LPA) was used to identify subgroups of older adults with distinct attentional function profiles. RESULTS: Three distinct attentional functional profiles were identified (i.e., low, moderate, and high attentional function). Compared to the high class, older adults in the low and moderate attentional function classes had lower functional status scores, a worse comorbidity profile and were more likely to be diagnosed with depression. In addition, QOL scores followed an expected pattern (low class < moderate class < high attentional function class). CONCLUSIONS: Three distinct attentional function profiles were identified among a relatively large sample of older adults undergoing CTX. The phenotypic characteristics associated with membership in the low and moderate latent classes can be used by clinicians to identify high risk patients.

Context Although physical function is an important patient outcome, little is known about changes in physical function in older adults receiving chemotherapy (CTX). Objectives Identify subgroups of older patients based on changes in their level of physical function; determine which demographic and clinical characteristics were associated with subgroup membership; and determine if these subgroups differed on quality-of-life (QOL) outcomes. Methods Latent profile analysis was used to identify groups of older oncology patients ( n = 363) with distinct physical function profiles. Patients were assessed six times over two cycles of CTX using the Physical Component Summary score from the Short Form 12. Differences, among the groups, in demographic and clinical characteristics and QOL outcomes were evaluated using parametric and nonparametric tests. Results Three groups of older oncology patients with distinct functional profiles were identified: Well Below (20.4%), Below (43.8%), and Above (35.8%) normative Physical Component Summary scores. Characteristics associated with membership in the Well Below class included the following: lower annual income, a higher level of comorbidity, being diagnosed with depression and back pain, and lack of regular exercise. Compared with the Above class, patients in the other two classes had significantly poorer QOL outcomes. Conclusion Almost 65% of older oncology patients reported significant decrements in physical function that persisted over two cycles of CTX. Clinicians can assess for those characteristics associated with poorer functional status to identify high-risk patients and initiate appropriate interventions.

Objectives Neutropenia is associated with the risk of life-threatening infections, chemotherapy dose reductions and delays that may compromise outcomes. This analysis was conducted to develop a prediction model for chemotherapy-induced severe neutropenia in lung cancer. Materials and Methods Individual patient data from existing cooperative group phase II/III trials of stages III/IV non-small cell lung cancer or extensive small-cell lung cancer were included. The data were split into training and testing sets. In order to enhance the prediction accuracy and the reliability of the prediction model, lasso method was used for both variable selection and regularization on the training set. The selected variables was fit to a logistic model to obtain regression coefficients. The performance of the final prediction model was evaluated by the area under the ROC curve in both training and testing sets. Results The dataset was randomly separated into training [7606 (67 %) patients] and testing [3746 (33 %) patients] sets. The final model included: age (>65 years), gender (male), weight (kg), BMI, insurance status (yes/unknown), stage (IIIB/IV/ESSCLC), number of metastatic sites (1, 2 or ≥3), individual drugs (gemcitabine, taxanes), number of chemotherapy agents (2 or ≥3), planned use of growth factors, associated radiation therapy, previous therapy (chemotherapy, radiation, surgery), duration of planned treatment, pleural effusion (yes/unknown), performance status (1, ≥2) and presence of symptoms (yes/unknown). Conclusions We have developed a relatively simple model with routinely available pre-treatment variables, to predict for neutropenia. This model should be independently validated prospectively.

Purpose Evaluate how subgroups of older adults with distinct attentional function profiles differ on the severity of nine common symptoms and determine demographic and clinical characteristics and symptom severity scores associated with membership in the low and moderate attentional function classes. Methods Three subgroups of older oncology outpatients were identified using latent profile analysis based on Attentional Function Index (AFI) scores. Symptoms were assessed prior to the second or third cycle of CTX. Logistic regressions evaluated for associations with attentional function class membership. Results For trait anxiety, state anxiety, depression, sleep disturbance, morning fatigue, and evening fatigue scores, differences among the latent classes followed the same pattern (low > moderate > high). For morning and evening energy, compared to high class, patients in low and moderate classes reported lower scores. For pain, compared to moderate class, patients in low class reported higher scores. In the logistic regression analysis, compared to high class, patients with lower income, higher comorbidity, higher CTX toxicity score, and higher levels of state anxiety, depression, and sleep disturbance were more likely to be in low AFI class. Compared to high class, patients with higher comorbidity and trait anxiety and lower morning energy were more likely to be in moderate AFI class. Conclusions Consistent with the hypothesis that an increased risk for persistent cognitive decline is likely related to a variety of physical and psychological factors, for six of the nine symptoms, a “dose response” effect was observed with higher symptom severity scores associated with a progressive decline in attentional function.

PURPOSE: While older adults with cancer are more likely to develop chemotherapy-induced peripheral neuropathy (CIPN), the study aimed to determine if patient-reported and objective measures of CIPN differ by age among cancer survivors. METHODS: Cancer survivors with persistent CIPN after completion of platinum and/or taxane chemotherapy completed CIPN questionnaires (severity, interference with activities, sensory and motor symptoms) and objective testing (light touch, vibration, pain, cold sensation). CIPN measures were compared by age group (

12044 Background: Older adults with poor prognosis cancers are more likely to experience toxicity from cancer-directed therapies. Although geriatric assessment (GA) reduces chemotherapy toxicity by detecting pre-existing conditions, GA can be difficult for oncologists to perform because of limited time and resources. We aim to determine the prevalence of pre-existing geriatric conditions that could be detected if GA were performed during routine oncology care. Methods: We used the Health and Retirement Study (HRS) linked with Medicare (1998-2016) to identify adults age >65 with poor prognosis cancers (median overall survival < 1 year). The HRS is a biennial nationally representative survey that asks about pre-existing geriatric conditions. Using the interview prior to the cancer diagnosis, we determined the presence of conditions included in GA: functional status (i.e. difficulty with climbing stairs, walking one block, getting up from a chair, bathing or showering, taking medications, and managing money), falls and injurious falls, unintentional weight loss, self-rated health, social support, mentation, advanced care planning, use of pain or sleep medications, and mobility. To identify groups with the highest prevalence of pre-existing geriatric conditions, we stratified results by age (adjusted for gender) and gender (adjusted for age). Results: Our study included 2,121 participants. At the time of cancer diagnosis, mean age was 76, 51% were female, 79% were non-Hispanic White, 26% had lung cancer, 14% had a GI cancer, and 60% had other metastatic cancers. Mean time between the HRS interview and cancer diagnosis was 12.7 months. The median overall survival of the entire cohort was 9.6 months with a 45% 1-year survival rate. The adjusted prevalence of pre-existing geriatric concerns were as follows: 65% had difficulty with climbing several flights of stairs, 27% had difficulty with walking one block, 47% had difficulty getting up from a chair after sitting down, 12% had difficulty in bathing or showering, 6% had difficulty taking medications, 11% had difficulty in managing money, 35% had a fall in the last 2 years with 12% of participants reporting injury after their fall. Those who were aged 85+, vs those aged 65-74, had higher rates of conditions indicative of cognitive impairment (e.g. 12 vs 4% had difficulty taking medications, p = 0.000, 26% vs 6% had difficulty managing money, p = 0.000) and physical impairments (e.g. 54% vs 30% had falls, respectively, p = 0.000). Rates of geriatric conditions indicative of physical impairment were higher in women vs men (e.g. 72% vs 58% had difficulty climbing stairs, p = 0.000 and 52% vs 41% had difficulty getting up from a chair, p = 0.000). Conclusions: Patients with poor prognosis cancers have high rates of pre-existing geriatric conditions that can be detected by GA. Geriatric assessments could find important impairments that could be addressed prior to cancer therapy to reduce adverse effects.

Purpose Under-representation of elderly, women, and racial/ethnic minority patients with cancer in clinical trials is of national concern. The goal of this study was to characterize enrollment trends and disparities by age, sex, and race/ethnicity in lung cancer trials. Methods We analyzed data for 23,006 National Cancer Institute cooperative group lung cancer trial participants and 578,476 patients with lung cancer from the SEER registry from 1990 to 2012. The enrollment disparity difference (EDD) and enrollment disparity ratio (EDR) were calculated on the basis of the proportion of each subgroup in the trial population and the US lung cancer population. Annual percentage changes (APCs) in the subgroup proportions in each population were compared over time. Results Enrollment disparity for patients ≥ 70 years of age with non–small-cell lung cancer improved from 1990 to 2012 (test of parallelism, P = .020), with a remaining EDD of 0.22 (95% CI, 0.19 to 0.25) and EDR of 1.65 (95% CI, 1.51 to 1.82) in 2010 to 2012. No improvement was seen for elderly patients with small-cell lung cancer (SCLC), with an APC of 0.20 ( P = .714) among trial participants, despite a rising proportion of elderly patients with SCLC in the US population (APC, 0.32; P = .020). Enrollment disparity for women with lung cancer improved overall, with the gap closing by 2012 (EDD, 0.03 [95% CI, 0.00 to 0.06]; EDR, 1.07 [95% CI, 1.00 to 1.16]). Enrollment disparities persisted without significant improvement for elderly women, blacks, Asians/Pacific Islanders, and Hispanics. Conclusion Under-representation in lung cancer trials improved significantly from 1990 to 2012 for elderly patients with non–small-cell lung cancer and for women, but ongoing efforts to improve the enrollment of elderly patients with SCLC and minorities are needed. Our study highlights the importance of addressing enrollment disparities by demographic and disease subgroups to better target under-represented groups of patients with lung cancer.

Chemotherapy-related cognitive impairment (CRCI) can occur during or after chemotherapy and represents a concern for many patients with cancer. Among older patients with cancer, in whom there is little clinical trial evidence examining side effects like CRCI, many unanswered questions remain regarding risk for and resulting adverse outcomes from CRCI. Given the rising incidence of cancer with age, CRCI is of particular concern for older patients with cancer who receive treatment. Therefore, research related to CRCI in older patients with cancers is a high priority. In this manuscript, we discuss current gaps in research highlighting the lack of clinical studies of CRCI in older adults, the complex mechanisms of CRCI, and the challenges in measuring cognitive impairment in older patients with cancer. Although we focus on CRCI, we also discuss cognitive impairment related to cancer itself and other treatment modalities. We highlight several research priorities to improve the study of CRCI in older patients with cancer.

Purpose Older adults receiving cancer chemotherapy are at increased risk for decrements in physical (PF) and cognitive (CF) function. Objectives Study identified subgroups of patients with distinct PF and CF profiles; risk factors associated with subgroup membership; and impact of subgroup membership on quality of life (QOL). Methods In 366 older oncology patients, PF and CF were assessed using the Physical Component Summary (PCS) of the SF-12 and Attentional Function Index, respectively. Latent profile analysis was used to identify subgroups of older patients with distinct PF/CF profiles. Results Three distinct PF/CF profiles were identified (i.e., Very Low PF + Moderate CF (15.6%); Low PF + Low CF (39.3%), Normal PF + Normal CF (45.1%)). Compared to the both Normal class, patients in the other two classes had a lower functional status, a worse comorbidity profile, and were less likely to exercise on a regular basis. Compared to the Both Normal class, patients in the Both Low class were less likely to be married/partnered, more likely to live alone, less likely to be employed, and more likely to report depression and back pain. Compared to the other two classes, patients in the Both Low class had a lower annual household income and were receiving chemotherapy with a worse toxicity profile. Conclusion First study to use a person-centered analytic approach to identify subgroups of older adults with distinct PF/CF profiles. Fifty-five percent of the older adults had statistically significant and clinically meaningful decrements in both PF AND CF that had negative effects on all aspects of QOL.

Key Points Question Is exposure to the National Comprehensive Cancer Center guidelines associated with decreased decisional conflict and increased rates of guideline-concordant care in patients with non–small cell lung cancer? Findings In this nonrandomized clinical trial, exposure to the National Comprehensive Cancer Center guidelines in 76 patients with non–small cell lung cancer was associated with increased smoking cessation counseling and decreased use of adjuvant chemotherapy after resection of early-stage disease. Use of the tool during consultation was also associated with decreased decisional conflict and greater satisfaction with their decision by the patients. Meaning The findings of this study suggest that use of cancer treatment guidelines is not in conflict with shared decision-making; increasing patients’ access to guidelines appears to improve the quality of oncologic care., Importance The association of guideline-based decision support with the quality of care in patients with non–small cell lung cancer (NSCLC) is not known. Objective To evaluate the association of exposure to the National Comprehensive Cancer Center (NCCN) guidelines with guideline-concordant care and patients’ decisional conflict. Design, Setting, and Participants A nonrandomized clinical trial, conducted at a tertiary care academic institution, enrolled patients from February 23, 2015, to September 28, 2017. Data analysis was conducted from July 19, 2019, to April 22, 2020. A cohort of 76 patients with NSCLC seen at diagnosis or disease progression and a retrospective cohort of 157 patients treated before the trial were included. Adherence to 6 NCCN recommendations were evaluated: (1) smoking cessation counseling, (2) adjuvant chemotherapy for patients with stage IB to IIB NSCLC after surgery, (3) pathologic mediastinal staging in patients with stage III NSCLC before surgery, (4) pathologic mediastinal staging in patients with stage III NSCLC before nonsurgical treatment, (5) definitive chemoradiotherapy for patients with stage III NSCLC not having surgery, and (6) molecular testing for epidermal growth factor receptor and anaplastic lymphoma kinase alterations for patients with stage IV NSCLC. Subgroup analysis was conducted to compare the rates of guideline concordance between the prospective and retrospective cohorts. Secondary end points included decisional conflict and satisfaction. Interventions An online tool customizing the NCCN guidelines to patients’ clinical and pathologic features was used during consultation, facilitated by a trained coordinator. Main Outcomes and Measures Concordance of practice with 6 NCCN treatment recommendations on NSCLC and patients’ decisional conflict. Results Of the 76 patients with NSCLC, 44 were men (57.9%), median age at diagnosis was 68 years (interquartile range [IQR], 41-87 years), and 59 patients (77.6%) had adenocarcinoma. In the retrospective cohort, 91 of 157 patients (58.0%) were men, median age at diagnosis was 66 years (IQR, 61-65 years), and 105 patients (66.9%) had adenocarcinoma. After the intervention, patients received more smoking cessation counseling (4 of 5 [80.0%] vs 1 of 24 [4.2%], P, This nonrandomized clinical trial examines the inclusion of National Comprehensive Cancer Network (NCCN) guidelines in a tool used by patients with non–small cell lung cancer to facilitate decision-making.

9570 Background: Osimertinib (osi) is a 3rd generation EGFR tyrosine kinase inhibitor (TKI) approved for first line (1L) treatment of metastatic NSCLC harboring EGFR Exon 19 del and L858R (representing > 80% of EGFR activating mutations) or in NSCLC with EGFRT790M (the most common resistance mutation to 1st or 2nd generation TKI). However, it has not been well-studied in EGFR-mutant NSCLC harboring less common EGFR activating mutations such as G719X, L861Q, S768I, and exon 20 insertion (ins), among others. Methods: We conducted a multi-institution, retrospective study approved on institutional IRB protocols in a series of patients (pts.) with metastatic NSCLC treated with osi who harbored at least one atypical EGFR mutation, excluding those with concurrent L858R, Exon 19 del, or T790M. Kaplan-Meier analyses were generated with SPSS, v25 (IBM Corp., USA). Response was assessed by RECIST 1.1 in evaluable pts. Time on osi was employed as a surrogate endpoint for clinical benefit in this retrospective analysis. Results: Fifty-one NSCLC pts with uncommon EGFR mutations were identified among six US institutions. Pt characteristics: 72.5% women, median age 65 yo (44-83 yo), 82.3% ECOG PS 0-1, 43.1% never smoker, 100% lung adenocarcinoma, 58.8% Caucasian, 25.5% Asian, 3.9% Black, 2.0% Hispanic, and 9.8% Other. The most frequent mutations were L861Q (35.3%, N = 18), G719X (27.5%, N = 14), and Exon 20 ins (15.7%, N = 8). Osi was used in the 1L setting in 39.2% (N = 20). Median time on osi was 7.1 months (mo.) in the overall cohort (95% CI, 5.4 to 8.8 mo.) and 8.9 mo. (95% CI, 7.0 to 10.8 mo.) in pts receiving 1L osi. Patients harboring G719X (N = 4) and L861Q (N = 10) mutations had a median time on 1L osimertinib of 5.8 mo. and 19.3 mo., respectively. One patient’s tumor had an EGFR exon 19 ins and was on 1L osi with a partial response for 16.8 months. Two patients with Exon 20 ins were on 1L osi for 9.3 mo. and 8 mo., respectively. Conclusions: In this largest known clinically annotated dataset of patients with atypical EGFR-mutations treated with osi, activity was noted, though 1L clinical benefit on osi appears lower in this multicenter US cohort than in E19del or L858R. These results are comparable to the recently published prospective phase II trial ( Cho et al, 2019) conducted in Korea. Patients with L861Q and Exon 19 insertion appeared to benefit the most from osi in this time on treatment retrospective analysis. More detailed analysis of this cohort is planned and further prospective studies are warranted to determine clinical benefit of osi amongst diverse atypical EGFR-mutations.

e24022 Background: Maintaining function and preventing functional decline during cancer treatment is critically important to older adults. This systematic review characterized and identified patient factors associated with functional change during systemic cancer therapy in older adults. Methods: Following PRISMA guidelines, we searched PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials for articles examining changes in function during systemic cancer treatment published in English through 1/11/19. Studies were eligible if they included adults age >65 and analyzed associations between patient factors and change in function. At least two independent investigators reviewed each article with discrepancies resolved by consensus. Major findings were summarized; no meta-analysis was planned a priori given the heterogeneity in studies. Results: We screened 15,244 titles/abstracts and 519 full texts. The final analysis included 69 studies, which enrolled > 11,000 patients with cancer. Most studies enrolled adults of all ages; 20% included only adults age >65 and 13% only adults age >70. A quarter of studies enrolled patients with lung cancer while 22% included all solid tumors and hematologic malignancies. The majority of studies evaluated function during chemotherapy (96%) with 9% including targeted therapy and 4% immunotherapy. Function was primarily measured with patient-reported outcomes (93% of studies). Reporting of functional change was heterogeneous with many reporting change scores or means at multiple time points. Among studies that reported the percentage of patients who developed functional decline, results ranged widely from 6% to 90%. Functional improvement occurred among 2% to 57% of patients. The most common patient factors associated with functional decline during systemic cancer therapy were older age (n = 8 studies), fatigue (n = 8), worse baseline performance status (n = 8) and physical activity (n = 5), and anemia (n = 5). Only 10 studies examined factors associated with functional recovery, identifying 12 unique patient factors. Conclusions: Among older adults with cancer, functional changes during systemic cancer therapy are common. Interventions to target modifiable patient factors associated with functional decline are needed to help patients maintain or improve function during treatment. Additionally, evaluating both functional decline and improvement is necessary to better characterize functional trajectories during systemic cancer therapy.

Purpose: Accurate comorbidity measurement is critical for cancer research. We evaluated comorbidity assessment in the National Cancer Database (NCDB), which uses a code-based Charlson-Deyo Comorbidity Index (CCI), and compared its prognostic performance with a chart-based CCI and individual comorbidities in a national sample of patients with breast, colorectal, or lung cancer. Patients and Methods: Through an NCDB Special Study, cancer registrars re-abstracted perioperative comorbidities for 11,243 patients with stage II to III breast cancer, 10,880 with stage I to III colorectal cancer, and 9,640 with stage I to III lung cancer treated with definitive surgical resection in 2006-2007. For each cancer type, we compared the prognostic performance of the NCDB code-based CCI (categorical: 0 or missing data, 1, 2+), Special Study chart-based CCI (continuous), and 18 individual comorbidities in three separate Cox proportional hazards models for postoperative 5-year overall survival. Results: Comorbidity was highest among patients with lung cancer (13.2% NCDB CCI 2+) and lowest among patients with breast cancer (2.8% NCDB CCI 2+). Agreement between the NCDB and Special Study CCI was highest for breast cancer (rank correlation, 0.50) and lowest for lung cancer (rank correlation, 0.40). The NCDB CCI underestimated comorbidity for 19.1%, 29.3%, and 36.2% of patients with breast, colorectal, and lung cancer, respectively. Within each cancer type, the prognostic performance of the NCDB CCI, Special Study CCI, and individual comorbidities to predict postoperative 5-year overall survival was similar. Conclusion: The NCDB underestimated comorbidity in patients with surgically resected breast, colorectal, or lung cancer, partly because the NCDB codes missing data as CCI 0. However, despite underestimation of comorbidity, the NCDB CCI was similar to the more complete measures of comorbidity in the Special Study in predicting overall survival.

To evaluate whether an association exists between the intensity of surveillance following surgical resection for non-small cell lung cancer (NSCLC) and survival.Surveillance guidelines following surgical resection of NSCLC vary widely and are based on expert opinion and limited evidence.A Special Study of the National Cancer Database randomly selected stage I to III NSCLC patients for data reabstraction. For patients diagnosed between 2006 and 2007 and followed for 5 years through 2012, registrars documented all postsurgical imaging with indication (routine surveillance, new symptoms), recurrence, new primary cancers, and survival, with 5-year follow-up. Patients were placed into surveillance groups according to existing guidelines (3-month, 6-month, annual). Overall survival and survival after recurrence were analyzed using Cox Proportional Hazards Models.A total of 4463 patients were surveilled with computed tomography scans; these patients were grouped based on time from surgery to first surveillance. Groups were similar with respect to age, sex, comorbidities, surgical procedure, and histology. Higher-stage patients received more surveillance. More frequent surveillance was not associated with longer risk-adjusted overall survival [hazard ratio for 6-month: 1.16 (0.99, 1.36) and annual: 1.06 (0.86-1.31) vs 3-month; P value 0.14]. More frequent imaging was also not associated with postrecurrence survival [hazard ratio: 1.02/month since imaging (0.99-1.04); P value 0.43].These nationally representative data provide evidence that more frequent postsurgical surveillance is not associated with improved survival. As the number of lung cancer survivors increases over the next decade, surveillance is an increasingly important major health care concern and expenditure.

Introduction Time-to-treatment-failure (TTF) is the interval from chemotherapy initiation to premature discontinuation. We evaluated TTF based on age. Methods Pooled analyses were conducted with first-line chemotherapy trials for advanced NSCLC (CALGB 9730, 30203, and 30801). Comparisons among patients who were 65 years and older and 70 years and older were performed for TTF (primary endpoint), reasons for early chemotherapy cessation, grade 3+ adverse events, and overall survival. Results Among 1006 patients, 460 (46%) were older than 65 years of age. One hundred forty-five older patients (32% of this age cohort) completed all six planned chemotherapy cycles as did 170 (32%) younger patients. Median TTF was 2.9 months (95% confidence interval: 2.7– 3.2) in older patients and 3 months (95% confidence interval: 2.9–3.5) in younger patients; adjustment for performance status and stratification by chemotherapy by trial yielded no statistically significant age-based difference in TTF. However, reasons for early chemotherapy cessation differed between age groups (multivariate p = 0.004). Older patients were less likely to discontinue from cancer progression (41% versus 55%) and more likely from toxicity or patient choice (16% and 15%, respectively) compared to younger patients (13% and 6%, respectively). Older patients were more likely to experience grade 3+ adverse events (86% versus 79%) with no statistically significant difference in survival. An age cutpoint of 70+ years showed no difference in TTF, a lower trend of early cessation due to cancer progression, and somewhat shorter older patient survival. Conclusions TTF was comparable between older and younger patients; but different, age-based, and potentially modifiable reasons account for it.