Search

Aim: To evaluate the comparative efficacy and safety of identified first-line therapies for patients with EGFR mutation-positive ( EGFRm+) advanced non-small-cell lung cancer (NSCLC), with a focus on ramucirumab + erlotinib. Methods: In the absence of head-to-head studies, a Bayesian network meta-analysis was conducted using randomized clinical trial data to evaluate first-line systemic therapies with erlotinib/gefitinib as the reference treatment. Results: For progression-free survival, ramucirumab + erlotinib was comparable to osimertinib and dacomitinib in the primary analysis. Conclusion: The analysis showed ramucirumab + erlotinib efficacy to be comparable to best-in-class treatment options for previously untreated patients with EGFRm+ advanced NSCLC. Registration information: PROSPERO ID: CRD42020136247

This retrospective, observational study examined patient characteristics, treatment patterns, testing patterns, and outcomes of US patients receiving first-/second- or third-generation epidermal gr...

Aim: To estimate real-world (rw) outcomes for first-line therapy in patients with advanced EGF receptor ( EGFR)-mutated non-small-cell lung cancer (NSCLC), focusing on specific mutation types. Patients & methods: Retrospective observational study (n = 244 patients). Results: Univariate/multivariate analyses showed longer rw progression-free survival (rwPFS) and rwPFS2 in patients with ex19del versus Leu858Arg mutations. Median overall survival was 12.3 months longer with ex19del versus Leu858Arg mutations (HR: 1.47 [95% CI: 0.96–2.25]; p = 0.074). With EGFR-tyrosine kinase inhibitor monotherapy, unadjusted rwPFS for ex19del mutations was longer than for Leu858Arg mutations (HR: 1.62 [95% CI: 1.03–2.56]; p = 0.036). Conclusion: In this rw cohort of patients with advanced EGFR+ NSCLC, ex19del mutations conferred a prognostic advantage over Leu858Arg mutations, with significantly better rwPFS and rwPFS2.

In the phase 3 RELAY trial, ramucirumab/erlotinib demonstrated superior progression-free survival (PFS) over placebo/erlotinib in patients with EGFR-mutated metastatic NSCLC (median PFS 19.4 versus...

Evidence from randomized controlled trials available for timely health technology assessments of new pharmacological treatments and regulatory decision making may not be generalizable to local patient populations, often resulting in decisions being made under uncertainty. In recent years, several reweighting approaches have been explored to address this important question of generalizability to a target population. We present a case study of the Innovative Medicines Initiative to illustrate the inverse propensity score reweighting methodology, which may allow us to estimate the expected treatment benefit if a clinical trial had been run in a broader real-world target population. We learned that identifying treatment effect modifiers, understanding and managing differences between patient characteristic data sets, and balancing the closeness of trial and target patient populations with effective sample size are key to successfully using this methodology and potentially mitigating some of this uncertainty around local decision making.

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

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).This study used an electronic health record-derived de-identified database. Eligible patients had advancedOf 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 underwentThe 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.

In the phase 3 RELAY trial, ramucirumab/erlotinib demonstrated superior progression-free survival (PFS) over placebo/erlotinib in patients withPatients received oral erlotinib (150 mg daily) plus intravenous ramucirumab (10 mg/kg) or placebo Q2W until progressive disease or unacceptable toxicity. Patients completed the Lung Cancer Symptom Scale (LCSS) and EQ-5D questionnaires at baseline and every other cycle. Analyses included time to deterioration (TtD) for LCSS via Kaplan-Meier method and Cox models and changes from baseline using mixed-model repeated-measures regression analysis.Overall patient compliance for LCSS and EQ-5D was95%. TtD did not differ between treatment arms for LCSS Total Score (HR = 0.962, 95% CI = 0.690-1.343) and Average Symptom Burden Index (HR = 1.012, 95% CI = 0.732-1.400). TtD of individual LCSS items (appetite loss, fatigue, cough, shortness of breath, pain, symptom distress, difficulties with daily activities, quality of life) indicated no difference between arms; however, patient-reported blood in sputum was worse for ramucirumab/erlotinib (HR = 1.987, 95% CI = 1.206-3.275). Results of LCSS mean changes from baseline were consistent with TtD, indicating no significant differences between treatment arms except for blood in sputum. Mean changes from baseline in EQ-5D index score (Patients' overall quality of life and symptom burden did not differ with the addition of ramucirumab to erlotinib compared to placebo/erlotinib. These data support the clinical benefit of ramucirumab/erlotinib in untreated

BACKGROUND The integration of data from disparate sources could help alleviate data insufficiency in real-world studies and compensate for the inadequacies of single data sources and short-duration, small sample size studies while improving the utility of data for research. OBJECTIVE This study aims to describe and evaluate a process of integrating data from several complementary sources to conduct health outcomes research in patients with non–small cell lung cancer (NSCLC). The integrated data set is also used to describe patient demographics, clinical characteristics, treatment patterns, and mortality rates. METHODS This retrospective cohort study integrated data from 4 sources: administrative claims from the HealthCore Integrated Research Database, clinical data from a Cancer Care Quality Program (CCQP), clinical data from abstracted medical records (MRs), and mortality data from the US Social Security Administration. Patients with lung cancer who initiated second-line (2L) therapy between November 01, 2015, and April 13, 2018, were identified in the claims and CCQP data. Eligible patients were 18 years or older and received atezolizumab, docetaxel, erlotinib, nivolumab, pembrolizumab, pemetrexed, or ramucirumab in the 2L setting. The main analysis cohort included patients with claims data and data from at least one additional data source (CCQP or MR). Patients without integrated data (claims only) were reported separately. Descriptive and univariate statistics were reported. RESULTS Data integration resulted in a main analysis cohort of 2195 patients with NSCLC; 2106 patients had CCQP and 407 patients had MR data. The claims-only cohort included 931 eligible patients. For the main analysis cohort, the mean age was 62.1 (SD 9.27) years, 48.56% (1066/2195) were female, the median length of follow-up was 6.8 months, and for 37.77% (829/2195), death was observed. For the claims-only cohort, the mean age was 66.6 (SD 12.69) years, 52.1% (485/931) were female, the median length of follow-up was 8.6 months, and for 29.3% (273/931), death was observed. The most frequent 2L treatment was immunotherapy (1094/2195, 49.84%), followed by platinum-based regimens (472/2195, 21.50%) and single-agent chemotherapy (441/2195, 20.09%); mean duration of 2L therapy was 5.6 (SD 4.9, median 4) months. We describe challenges and learnings from the data integration process, and the benefits of the integrated data set, which includes a richer set of clinical and outcome data to supplement the utilization metrics available in administrative claims. CONCLUSIONS The management of patients with NSCLC requires care from a multidisciplinary team, leading to a lack of a single aggregated data source in real-world settings. The availability of integrated clinical data from MRs, health plan claims, and other sources of clinical care may improve the ability to assess emerging treatments.

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC.

In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC).To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC.A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively.Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P0.05). Additionally, increasing patient out-of-pocket cost was associated with decreasing adherence to erlotinib (P0.0001). Factors significantly related to longer treatment duration included low-income subsidy status (P0.001) and having Medicare insurance, (P = 0.0004), dual eligibility (Medicare and Medicaid, P = 0.007), and higher erlotinib out-of-pocket costs (P0.0001).There is a need for mechanisms to be in place to identify and address barriers to care. Future research should focus on evaluating and reducing any potential risk to patient outcomes that may be associated with low adherence to or shorter treatment duration on oral chemotherapy.This study was supported by funding from Eli Lilly and Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data interpretation was performed by all the authors. The manuscript was written primarily by Hess, along with Nair, and revised by Hess, Nair, Louder, and Winfree, with assistance from Zhu and Louder.

Objective: To analyze patient-reported swallowing difficulties, healthcare resource utilization and associated costs during the PROCLAIM study. Methods: Patients with stage III non-squamous non-small cell lung cancer received pemetrexed-cisplatin (PemCis) combined with concurrent thoracic radiotherapy followed by consolidation pemetrexed, or concurrent chemoradiotherapy with etoposide-cisplatin (EtoCis) followed by standard consolidation chemotherapy. Patient - reported swallowing function was measured using diaries. Resource utilization (hospitalizations, transfusions, concomitant medications) was compared between treatment arms using Fisher’s exact test and independent t-test. Medical resource use costs were analyzed using nonparametric Wilcoxon rank sum test. Results: Patient-reported difficulty in swallowing function (diary score ≥4) was 33.8% in the PemCis arm and 29% in the EtoCis arm. Overall resource use, including hospitalizations, was similar between treatment arms; however, fewer patients in the PemCis arm received transfusions and selected concomitant medications. Concurrent phase analyses were consistent with the overall study. A significantly lower percentage of patients (31.1% vs. 40.8%) were hospitalized in the PemCis arm. Total costs were significantly higher in the PemCis arm. Other medical costs (excluding study treatment costs) during the concurrent phase were lower for patients in the PemCis arm, due to significantly lower hospitalization costs and lower use of concomitant medications. Subgroup analysis yielded similar results. Conclusions: Patient-reported difficulty in swallowing post-baseline and resource utilization were consistent with previously reported safety outcomes. In the overall study, higher total costs for PemCis were driven by study drug cost. When adjusting for treatment duration, other monthly medical costs were favorable to PemCis. Patients on pemetrexed remained longer on therapy, suggesting better tolerability. ClinicalTrials.gov identifier: NCT00686959.

Background The integration of data from disparate sources could help alleviate data insufficiency in real-world studies and compensate for the inadequacies of single data sources and short-duration, small sample size studies while improving the utility of data for research. Objective This study aims to describe and evaluate a process of integrating data from several complementary sources to conduct health outcomes research in patients with non–small cell lung cancer (NSCLC). The integrated data set is also used to describe patient demographics, clinical characteristics, treatment patterns, and mortality rates. Methods This retrospective cohort study integrated data from 4 sources: administrative claims from the HealthCore Integrated Research Database, clinical data from a Cancer Care Quality Program (CCQP), clinical data from abstracted medical records (MRs), and mortality data from the US Social Security Administration. Patients with lung cancer who initiated second-line (2L) therapy between November 01, 2015, and April 13, 2018, were identified in the claims and CCQP data. Eligible patients were 18 years or older and received atezolizumab, docetaxel, erlotinib, nivolumab, pembrolizumab, pemetrexed, or ramucirumab in the 2L setting. The main analysis cohort included patients with claims data and data from at least one additional data source (CCQP or MR). Patients without integrated data (claims only) were reported separately. Descriptive and univariate statistics were reported. Results Data integration resulted in a main analysis cohort of 2195 patients with NSCLC; 2106 patients had CCQP and 407 patients had MR data. The claims-only cohort included 931 eligible patients. For the main analysis cohort, the mean age was 62.1 (SD 9.27) years, 48.56% (1066/2195) were female, the median length of follow-up was 6.8 months, and for 37.77% (829/2195), death was observed. For the claims-only cohort, the mean age was 66.6 (SD 12.69) years, 52.1% (485/931) were female, the median length of follow-up was 8.6 months, and for 29.3% (273/931), death was observed. The most frequent 2L treatment was immunotherapy (1094/2195, 49.84%), followed by platinum-based regimens (472/2195, 21.50%) and single-agent chemotherapy (441/2195, 20.09%); mean duration of 2L therapy was 5.6 (SD 4.9, median 4) months. We describe challenges and learnings from the data integration process, and the benefits of the integrated data set, which includes a richer set of clinical and outcome data to supplement the utilization metrics available in administrative claims. Conclusions The management of patients with NSCLC requires care from a multidisciplinary team, leading to a lack of a single aggregated data source in real-world settings. The availability of integrated clinical data from MRs, health plan claims, and other sources of clinical care may improve the ability to assess emerging treatments.

53 Background: Pembrolizumab (Pembro) is used in first-line treatment of patients with metastatic non-squamous non-small cell lung cancer (NSQ NSCLC) as monotherapy and in combination with pemetrexed and platinum agent (Pembro+Pem+Plat). Pembro monotherapy is approved for patients whose tumors express PD-L1 Tumor Proportion Score (TPS) ≥ 1% while triplet therapy is approved regardless of PD-L1 TPS. These 2 regimens have not been compared in a head-to-head trial, and real world (RW) treatment pattern data are lacking. This study used RW data to describe patients who received Pembro or Pembro+Pem+Plat and associated overall survival (OS). Methods: This retrospective observational study selected adult patients with diagnosis of advanced NSQ NSCLC who started first-line treatment with Pembro or Pembro+Pem+Plat between Mar. 2015- Aug. 2018 in Flatiron Health’s electronic health record-derived database. Patient characteristics were summarized descriptively, and the Kaplan-Meier survival method was used (unadjusted). Results: A total of 1137 patients received Pembro (median age 72 years) and 1068 patients received Pembro+Pem+Plat (median age 67 years). Patient characteristics are shown in the Table. Median OS was 11.9 months for the Pembro cohort and 14.3 months for the Pembro+Pem+Plat cohort. Median OS by PD-L1 TPS was TPS < 1%: 8.8 months for Pembro and 9.5 months for Pembro+Pem+Plat, TPS 1-49%: 8.9 months for Pembro and not reached (NR) for Pembro+Pem+Plat, and TPS ≥50%: 13.4 months for Pembro and NR for Pembro+Pem+Plat. Conclusions: These RW data seem to suggest baseline differences between the population with Pembro and Pembro+Pem+Plat with regard to age, PS, disease stage, as well as PD-L1 status. Those baseline differences may play a role in the clinicians’ choice of the two treatment options for the NSCLC patients. [Table: see text]

52 Background: Immunotherapy (IO) for initial treatment of patients with advanced non-squamous non-small cell lung cancer (nsqNSCLC) has led to improved progression free survival (PFS) and overall survival (OS) vs chemotherapy. The objective of this network meta-analysis (NMA) was to compare the efficacy of IO-based therapies to chemotherapy in the first-line treatment until progression for advanced nsqNSCLC. Methods: A systematic literature review was conducted to identify randomized controlled trials reporting PFS and/or OS data in adult patients who received first-line treatment for stage IIIB or IV nsqNSCLC until progression. MEDLINE, EMBASE and Cochrane Central Register were searched from the start of databases to June 2018. The NMA used fixed-effects models to estimate hazard ratios (HRs) and credible intervals (Crl) for PFS and OS of IO therapies vs pemetrexed + platinum. A subgroup of patients with PD-L1 tumor proportion score (TPS) ≥50% was also analysed. Results: Evidence networks comprised of 18 studies for the overall population and 3 studies for the PD-L1 TPS ≥50% subgroup. In PFS analysis for the overall population, HRs were lower for atezolizumab + bevacizumab + paclitaxel + platinum (HR 0.62; 95% CrI 0.48, 0.8), ipilimumab + nivolumab (HR 0.55; 95% CrI 0.38, 0.8) and pemetrexed + pembrolizumab + platinum regimens (HR 0.52; 95% CrI 0.43, 0.63) vs pemetrexed + platinum. In the PD-L1 TPS ≥50% subgroup, PFS HRs were lower for pembrolizumab (HR 0.81; 95% CrI 0.67, 0.98) and pemetrexed + pembrolizumab + platinum (HR 0.36; 95% CrI 0.25, 0.52) vs pemetrexed + platinum. In the OS analysis for the overall population, pemetrexed + pembrolizumab + platinum had a lower HR (HR 0.5; 95% CrI 0.4, 0.64) vs pemetrexed + platinum. This difference in OS was magnified in the PD-L1 TPS ≥50% subgroup (HR 0.42; 95% CrI 0.26, 0.68). Conclusions: Among all IO-based therapies in this analysis, pemetrexed + pembrolizumab + platinum had the highest PFS and OS benefit vs pemetrexed + platinum in the first-line treatment until progression for advanced nsqNSCLC for both the overall population and high PD-L1 subgroup. These comparative efficacy data may inform clinicians in treatment selection.

In patients with non-squamous non-small-cell lung cancer (NSCLC), maintenance therapy regimens, including pemetrexed, have been shown to prolong overall survival (OS) and progression-free survival (PFS). The purpose of this study was to describe real-world maintenance use of pemetrexed and associated outcomes in patients with advanced NSCLC.This was a retrospective, observational study that used longitudinal, demographically and geographically diverse electronic health record data in the United States. Eligible patients were adults with advanced non-squamous NSCLC who had received maintenance treatment with pemetrexed monotherapy or pemetrexed plus bevacizumab. Descriptive statistics were used to describe the patient population and multivariable logistic regression was used to identify the factors associated with duration of maintenance therapy. Kaplan-Meier curves and Cox regression models were used for time-to-event analysis.Patients receiving pemetrexed maintenance therapy were treated with either pemetrexed monotherapy (66.0%) or pemetrexed plus bevacizumab (34.0%). Carboplatin and pemetrexed (37.9%) or carboplatin, pemetrexed and bevacizumab (36.1%) were the most commonly used first-line therapies observed. The majority (84.9%) of these maintenance patients responded to first-line therapy. The median duration of maintenance therapy was 6.0 months for pemetrexed and bevacizumab and 4.1 months for pemetrexed monotherapy. The median OS from the start of first-line therapy of the total study cohort was 21.5 months (95% CI 20.0, 22.9).Real-world effectiveness of pemetrexed maintenance therapy is similar to that observed in published randomized controlled trials, confirming a role for pemetrexed maintenance in eligible patients in clinical practice.

Introduction Advanced non-small cell lung cancer (NSCLC) is a severe disease with burdensome symptoms and traditionally poor outcomes. The treatment of advance disease is based on chemotherapy, with the recent addition of immunotherapy. Patients who respond to initial treatment can opt to receive maintenance therapy (MT). It is important to understand why patients with advanced NSCLC choose to accept or refuse therapy, and how physician recommendations play into this decision-making process. This study characterized patient and physician decision-making regarding treatment for patients with advanced non-squamous NSCLC in the USA using the example of MT. Methods and Materials This study employed multiple approaches: patient interviews, a patient survey, and a physician survey. Qualitative interviews were conducted among patients who had been offered MT to identify factors influencing treatment decision-making. The patient survey explored the decision-making process and quantified challenges and motivators for receiving MT. The physician survey included a discrete choice experiment to understand the relationship between physician treatment recommendations and patient characteristics. Results Interviewed patients (n = 10) were motivated to receive MT in the hope of extending their lives and being proactive against their cancer, and they anticipated reduced adverse effects compared with first-line therapy. Surveyed patients (n = 77) described several deterrents to receiving therapy; the most prominent was severity of adverse effects, which was an influencing factor for 34% of patients. The major motivator for receiving therapy was the potential to extend life, which influenced 97% of patients. A total of 100 oncologists participated in the physician survey. Patients’ lack of treatment motivation/inconvenience, disease progression, presence of severe renal co-morbidities, and older age decreased the likelihood of physicians recommending the use of MT. Conclusion This study identified challenges and motivators influencing advanced NSCLC patients’ decisions to accept or refuse therapy, as well as patient and disease characteristics associated with physician’s treatment recommendations for MT. Electronic supplementary material The online version of this article (10.1007/s40271-018-0327-3) contains supplementary material, which is available to authorized users.

Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting. This population-based study aimed to evaluate treatment patterns at a national level in the USA. This retrospective observational study used data from the US Oncology Network’s iKnowMed database. Patients with advanced NSCLC who initiated first-line therapy with erlotinib and/or intravenous chemotherapy between January 1, 2012 and June 30, 2015 and met all other study criteria were included. Descriptive analyses assessed demographic and clinical characteristics and treatment patterns among the overall study cohort, as well as for specific erlotinib treatment subgroups, stratified by EGFR status. Among the 3108 patients identified, 18.5% were EGFR positive, 49.8% were EGFR negative, and 31.7% were EGFR documented unknown. For the overall cohort, 18.4% received first-line erlotinib monotherapy, fewer than 1% received first-line combination therapy (erlotinib plus chemotherapy), 4.7% received second-line erlotinib monotherapy, and 3.3% received second-line combination therapy. First-line erlotinib monotherapy was used in 77.8% of all EGFR positive patients. Almost two-thirds of the overall cohort were not observed to have advanced to second-line therapy. As treatment options evolve, this study provides real-world treatment patterns that suggest concordance with NCCN guidelines and confirm the remaining need to understand sequencing of therapies and related outcomes. Eli Lilly and Company.

The REVEL study demonstrated improved efficacy with ramucirumab plus docetaxel versus placebo plus docetaxel for previously treated advanced/metastatic non-small-cell lung cancer (NSCLC) without further detriment to patient quality of life, symptoms, or functioning. This post hoc analysis explored the association between baseline Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index (ASBI) and efficacy.Baseline ASBI scores were the average of the 6 LCSS symptom components. Low and high symptom burden (LSB ≤ median, HSB median) were analyzed across and by treatment arms for effects on overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) using the Kaplan-Meier method and Cox proportional hazards model.Baseline LCSS compliance was approximately 78% in both REVEL treatment arms. Patients with LSB versus HSB had fewer poor prognostic factors. The HSB patient population significantly overlapped with previously identified aggressive disease subgroups (rapidly progressing disease or refractory to first-line treatment). Patients with LSB versus HSB had significantly improved OS (P 0.0001), PFS (P 0.0001), and ORR (P = 0.0003) regardless of treatment, with superior ORR and PFS but not OS in the ramucirumab plus docetaxel arm. Patients with HSB treated with ramucirumab plus docetaxel versus docetaxel had improved OS (median, 7.39 vs. 5.95 months; HR 0.749 [95% CI 0.610-0.920]; P = 0.0308), PFS (median, 4.01 vs. 2.63 months; HR 0.749 [0.619-0.907]; P = 0.0202), and ORR (18% vs. 11%; P = 0.0458). Of patients with rapidly progressing disease, 57% (92/162) also had HSB.Baseline ASBI may be an independent prognostic factor in this large second-line cohort of patients with advanced NSCLC. The preservation of improved PFS and OS in the HSB cohort suggests that the addition of ramucirumab to docetaxel provides benefit in patients with greater symptom burden, consistent with previous data on REVEL patients with aggressive disease.

IntroductionTreatment impact on quality of life (QoL) informs treatment management decisions in advanced nonsquamous non–small-cell lung cancer (NS NSCLC). QoL outcomes from the phase III PointBreak trial are reported.MethodsChemonaive patients (n = 939) with stage IIIB/IV nonsquamous non–small-cell lung cancer and Eastern Cooperative Oncology Group performance status 0 to 1 were randomized (1:1) to pemetrexed-carboplatin-bevacizumab (pemetrexed arm) or paclitaxel-carboplatin-bevacizumab (paclitaxel arm). Patients without progressive disease received maintenance pemetrexed-bevacizumab (pemetrexed arm) or bevacizumab (paclitaxel arm). QoL was assessed using Functional Assessment of Cancer Therapy (FACT)-General (FACT-G), FACT-Lung (FACT-L), and FACT/Gynecologic Oncology Group-Neurotoxicity (FACT-Ntx) instruments. Subscale scores, total scores, and trial outcome indices were analyzed using linear mixed-effects models. Post hoc analyses examined the association between baseline FACT scores and overall survival (OS).ResultsMean score differences in change from baseline significantly favored the pemetrexed arm for the neurotoxicity subscale score, FACT-Ntx total scores, and FACT-Ntx trial outcome index. They occurred at cycle 2 (p < 0.001) and persisted through induction cycles 2 to 4 and six maintenance cycles. Investigator-assessed, qualitative, drug-related differences in grade 2 (1.6% versus 10.6%) and grade 3 (0.0% versus 4.1%) sensory neuropathy and grade 3/4 fatigue (10.9% versus 5.0%, p = 0.0012) were observed between the pemetrexed and paclitaxel arms. Baseline FACT-G, FACT-L, and FACT-Ntx scores were significant prognostic factors for OS (p < 0.001).ConclusionsRandomized patients reported similar changes in QoL, except for less change from baseline in neurotoxicity on the pemetrexed arm; investigators reported greater neurotoxicity on the paclitaxel arm and greater fatigue on the pemetrexed arm. Higher baseline FACT scores were favorable prognostic factors for OS.

Introduction PRONOUNCE compared the efficacy and safety of pemetrexed+carboplatin followed by pemetrexed (Pem+Cb) with paclitaxel+carboplatin+bevacizumab followed by bevacizumab (Pac+Cb+Bev) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC). Methods Patients ≥18 years of age with stage IV nonsquamous NSCLC (American Joint Committee on Cancer v7.0), and Eastern Cooperative Oncology Group performance status 0/1 were randomized (1:1) to four cycles of induction Pem+Cb (pemetrexed, 500 mg/m 2 , carboplatin, area under the curve=6) followed by Pem maintenance or Pac+Cb+Bev (paclitaxel, 200 mg/m 2 , carboplatin, area under the curve=6, and bevacizumab, 15 mg/kg) followed by Bev maintenance in the absence of progressive disease or discontinuation. The primary objective was progression-free survival (PFS) without grade 4 toxicity (G4PFS). Secondary end points were PFS, overall survival (OS), overall response rate (ORR), disease control rate (DCR), and safety. Resource utilization was also assessed. Results Baseline characteristics of the patients randomized to Pem+Cb (N = 182) and Pac+Cb+Bev (N = 179) were well balanced between the arms. Median (months) G4PFS was 3.91 for Pem+Cb and 2.86 for Pac+Cb+Bev (hazard ratio=0.85, 90% confidence interval, 0.7–1.04; p = 0.176); PFS, OS, ORR, or DCR did not differ significantly between the arms. Significantly more drug-related grade 3/4 anemia (18.7% versus 5.4%) and thrombocytopenia (24.0% versus 9.6%) were reported for Pem+Cb. Significantly more grade 3/4 neutropenia (48.8% versus 24.6%), grade 1/2 alopecia (28.3% versus 8.2%), and grade 1/2 sensory neuropathy were reported for Pac+Cb+Bev. Number of hospitalizations and overall length of stay did not differ significantly between the arms. Conclusions Pem+Cb did not produce significantly better G4PFS compared with Pac+Cb+Bev. Pem+Cb was not superior in PFS, OS, ORR, or DCR compared with Pac+Cb+Bev. Both regimens were well tolerated, although, toxicity profiles differed.

Background: Survival outcomes are related to treatment choices in a line of therapy and to treatment sequences across all lines of therapy. Objective: The Real-World Treatment Sequences and Outcomes among Patients with NSCLC (RESOUNDS) study is designed to (1) evaluate treatment sequences used for patients who receive at least two lines of therapy for non-small cell lung cancer (NSCLC) in the United States and (2) evaluate patient outcomes in terms of progression-free and overall survival related to treatment sequencing. Additional objectives include the evaluation of symptoms, comorbidities, and health care resource utilization and costs. Methods: Patients will be censored at loss to follow-up due to leaving the health plan or reaching the end of the study period. Results: This study is ongoing. Conclusions: The RESOUNDS cohort study is a novel approach to building a comprehensive dataset that mimics a prospective observational study using linked patient-level data from four real-world data sources. This study will provide timely information on the sequencing of treatments for patients with NSCLC.

Kaisa Taipale,1 Katherine B Winfree,2 Mark Boye,2 Mickael Basson,3 Ghassan Sleilaty,4 James Eaton,5 Rachel Evans,5 Christos Chouaid6 1Global Patient Outcomes and Real World Evidence International, Oy Eli Lilly Finland AB, Helsinki, Finland; 2Global Patient Outcomes and Real World Evidence, Eli Lilly and Company, Indianapolis, IN, USA; 3Corporate Affairs, Lilly France, Neuilly-sur-Seine, 4Bio-Medicines Medical Affairs, Lilly France, Neuilly-sur-Seine, France; 5ICON Health Economics and Epidemiology, ICON Plc, Milton Park, UK; 6Thoracic Oncology, Service de Pneumologie, Centre Hospitalier Intercommunal Créteil, Créteil, France Background: Comparative effectiveness and cost-effectiveness data for induction–maintenance (I–M) sequences for the treatment of patients with nonsquamous non-small-cell lung cancer (nsqNSCLC) are limited because of a lack of direct evidence. This analysis aimed to compare the cost-effectiveness of I–M pemetrexed with those of other I–M regimens used for the treatment of patients with advanced nsqNSCLC in the French health-care setting. Materials and methods: A previously developed global partitioned survival model was adapted to the France-only setting by restricting treatment sequences to include 12 I–M regimens most relevant to France, and incorporating French costs and resource-use data. Following a systematic literature review, network meta-analyses were performed to obtain hazard ratios for progression-free survival (PFS) and overall survival (OS) relative to gemcitabine + cisplatin (induction sequences) or best supportive care (BSC) (maintenance sequences). Modeled health-care benefits were expressed as life-years (LYs) and quality-adjusted LYs (QALYs) (estimated using French EuroQol five-dimension questionnaire tariffs). The study was conducted from the payer perspective (National Health Insurance). Cost- and benefit-model inputs were discounted at an annual rate of 4%. Results: Base-case results showed pemetrexed + cisplatin induction followed by (→) pemetrexed maintenance had the longest mean OS and PFS and highest LYs and QALYs. Costs ranged from €12,762 for paclitaxel + carboplatin → BSC to €35,617 for pemetrexed + cisplatin → pemetrexed (2015 values). Gemcitabine + cisplatin → BSC, pemetrexed + cisplatin → BSC, and pemetrexed + cisplatin → pemetrexed were associated with fully incremental cost-effectiveness ratios (ICERs) of €16,593, €80,656, and €102,179, respectively, per QALY gained versus paclitaxel + carboplatin → BSC. All other treatment sequences were either dominated (ie, another sequence had lower costs and better/equivalent outcomes) or extendedly dominated (ie, the comparator had a higher ICER than a more effective comparator) in the model. Sensitivity analyses showed the model to be relatively insensitive to plausible changes in the main assumptions, with none increasing or decreasing the ICER by more than ~€20,000 per QALY gained. Conclusion: In the absence of direct comparative trial evidence, this cost-effectiveness analysis indicated that of a large number of I–M sequences used for the treatment of patients with nsqNSCLC in France, pemetrexed + cisplatin → pemetrexed achieved the best clinical outcomes (0.28 incremental QALYs gained) versus paclitaxel + carboplatin → BSC. Keywords: advanced nonsquamous NSCLC, cost-effectiveness, France, induction–maintenance, pemetrexed, quality-adjusted life-years

Introduction Ramucirumab, a recombinant human immunoglobulin G1 monoclonal antibody receptor antagonist designed to block the ligand-binding site of vascular endothelial growth factor receptor-2 (VEGFR-2), was evaluated as second-line treatment in combination with docetaxel in patients with non–small-cell lung cancer in the REVEL trial ( NCT01168973 ). Ramucirumab significantly improved overall survival (OS) and progression-free survival (PFS). We report age subgroup analysis results primarily on the basis of a 65-year cutoff. Patients and Methods Patients were randomized 1:1 to ramucirumab with docetaxel or placebo with docetaxel (n = 1253). Of these, 798 were younger than 65 years (ramucirumab, n = 391; control, n = 407) and 455 were 65 years or older (ramucirumab, n = 237; control, n = 218). Treatment comprised 21-day cycles of 75 mg/m2 docetaxel with 10 mg/kg ramucirumab or placebo. Prespecified age subgroup analyses were performed, including OS, PFS, and objective response rate. Quintiles age analysis was conducted to establish a relationship between efficacy and age. The Lung Cancer Symptom Scale (LCSS) measured quality of life outcomes. Safety was assessed according to adverse events (AEs). Results Patients younger than 65 years showed favorable OS outcomes with ramucirumab treatment (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.62-0.87; P Conclusion In this subgroup analysis, true treatment effect differences on the basis of age have not been established, and treatment should not be deterred solely because of age.

Background RELAY showed significantly improved progression free survival (PFS) for RamErl over PboErl in patients with EGFR+ mNSCLC, (mPFS 19.4 vs 12.4 mo; HR 0.59, 95%CI 0.46-0.76; p Methods Eligible patients were randomized (1:1) to receive 150 mg daily oral Erl plus 10 mg/kg intravenous Ram or Pbo Q2W until progressive disease or unacceptable toxicity. Patients completed the Lung Cancer Symptom Scale (LCSS) and the EQ-5D at baseline, every other cycle, and the 30-day follow-up visit. Two pre-specified analyses, time to deterioration (TtD) for LCSS (secondary endpoint) and TtD in Eastern Cooperative Oncology Group performance status (ECOG PS) (exploratory endpoint) were analyzed using the Kaplan Meier method and Cox models. Changes from baseline were analyzed using a mixed-model repeated measures regression analysis. Results Patients (93.7%) maintained ECOG PS 0/1 in both arms until progression; thus, a TtD analysis was not feasible. Overall patient compliance for LCSS and EQ-5D was high (>95%). TtD for LCSS total score (HR = 0.96 [95% CI: 0.69-1.34] and average symptom burden index TtD (HR = 1.01 [95% CI: 0.73-1.40]) did not differ between treatment arms. TtD of individual LCSS items (appetite loss, fatigue, cough, shortness of breath, blood in sputum [hemoptysis], and pain; symptom distress, difficulties with daily activities, and quality of life) indicated no difference between arms, except in patient-reported hemoptysis (HR = 1.99 [95% CI: 1.21, 3.28]), which favored the PboErl arm. LCSS mean changes from baseline were consistent with TtD. Mean changes from baseline in EQ-5D index score (p = 0.94) and VAS (p = 0.95) revealed no overall differences in health status between treatment arms. Conclusions The addition of Ram to Erl does not impair patient-focused outcomes in RELAY. These quality of life data support the clinical benefit of RamErl in untreated EGFR+ mNSCLC. Clinical trial identification NCT02411448. Editorial acknowledgement Susan P. Whitman, a full-time employee of Eli Lilly and Company, provided medical writing and editing support. Legal entity responsible for the study Eli Lilly and Company. Funding Eli Lilly and Company. Disclosure K. Yoh: Honoraria (self), Research grant / Funding (institution): Eli Lilly and Company, Taiho, Novartis, Ono, AstraZeneca, Chugai; Research grant / Funding (institution): Bayer, Pfizer; Honoraria (self): BMS. S. Atagi: Honoraria (self), Honoraria (institution), financial interests euro500-20000p.a.: AZ, Chugai, MSD, Ono, Taiho, BI, Pfizer, BMS, Eli Lilly; Honoraria (institution), interests euro >250000p.a.: Hoffmann-LaRoche. M. Reck: Honoraria (self), Advisory / Consultancy: AbbVie, Amgen, AZ, BMS, BI, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. E.B. Garon: Research grant / Funding (institution): AZ, BMS, Lilly, Genentech, Merck, Novartis, Iovance, Neon, Dynavax, Mirati; Advisory / Consultancy, advisory board and steering committee : Dracen, EMD Serono. S. Ponce Aix: Speaker Bureau / Expert testimony: Lilly. D. Moro-Sibilot: Advisory / Consultancy: Roche, BMS, MSD, Takeda, Pfizer, Novartis, AZ, Lilly, BI. K.B. Winfree: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. B. Frimodt-Moller: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. A.H. Zimmermann: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. C.M. Visseren-Grul: Shareholder / Stockholder / Stock options, Full / Part-time employment: Eli Lilly and Company. K. Nakagawa: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): MSDKK, Eli Lilly Japan KK, BMS, Taiho, Ono, Chugai, AZ KK, Astellas Pharma, Novartis Pharma KK, Nippon BI, Pfizer Japan; Travel / Accommodation / Expenses: Eli Lilly and Company.

e20706 Background: Despite advances in therapy, recent observational data shows that aNSCLC pts with RDP continue to have a poor prognosis. This retrospective, observational study characterizes the demographic, molecular, & treatment profile of pts with RDP. Methods: Adult aNSCLC pts receiving first-line (1L) platinum-based (Pt) therapy between 01/2014 - 12/2018 were identified in the COTA Real-World Evidence database and assigned to RDP (n = 280) & non-RDP (n = 1,212) cohorts based on time to progression during 1L Pt therapy (≤ 12 and > 12 weeks, respectively). Results: Of 1,492 eligible pts, the incidence of RDP was 19%. Mean age (±SD) was 64.6 (10.9) and 66.1 (10.2) in the RDP and non-RDP group, respectively (p = 0.04). Data showed RDP patients had higher percentage of stage IV disease at diagnosis (77 v 72, p < 0.01), higher histologic grade G3/G4 (37 v 29, p = 0.01), and PD-L1 negative (< 1% expression) status (p = 0.01). Table shows molecular profiling across cohorts. No notable difference in treatment patterns across 1L and 2L was observed. Conclusions: This study identifies stage IV disease at diagnosis, higher grade, & PD-L1 negative ( < 1% expression) as potential risk factors for RDP. A better understanding of this poor prognosis cohort may offer an opportunity to better optimize therapies & outcomes. [Table: see text]

e20723 Background: Clinical trials have shown that aNSCLC patients (pts) with AD, including those with rapid disease progression (RDP) on initial therapy (time to progression ≤ 12 weeks), have poor prognosis. This retrospective study evaluates the real world clinical burden associated with AD, defined as the difference in clinical effectiveness outcomes during subsequent treatment following RDP v non-RDP on platinum-based (Pt) therapy. Methods: Adult aNSCLC pts receiving standard post-Pt progression therapy (immune checkpoint inhibitors, single agent chemo, ramucirumab) between 03/01/2015 and 06/30/2018, after Pt therapy, with ≥ 3 months of potential follow up, were identified in the Flatiron EHR-derived deidentified database and assigned to RDP (n = 158) and non-RDP (n = 518) cohorts. Real-world tumor response (rwTR) was collected using technology-enabled abstraction. Overall survival (OS) from start of 1L, and real-world (rw) progression free survival (PFS) & rw tumor response outcomes (rw objective response rate [rwORR], rw disease control rate [rwDCR], rw time to first response [rwTTFR], rw duration of response [rwDOR] & rw best response [rwBR]) during post-Pt progression therapy were estimated. Results: Of 676 eligible pts, 23% had RDP. Clinical outcomes in the RDP and non-RDP cohorts are shown in table. Conclusions: Findings from this real world cohort underscore the clinical burden & unmet medical need for more effective treatment strategies in pts with aggressive aNSCLC pts who rapidly progress on initial therapy. As the treatment landscape evolves, characterization of these pts is warranted to identify potential risk factors. [Table: see text]

e20725 Background: In REVEL, adding ramucirumab to docetaxel improved response rates among Pt-treated aNSCLC pts. This observational study evaluated rwTR in aNSCLC pts treated with R+D after Pt & ICI or other (non-ICI) therapies. Methods: Adult aNSCLC pts receiving 2L/3L R+D between 3/1/15 & 6/30/18, after 1L/2L Pt therapy, with ≥ 1 documented rwTR assessment, & ≥ 3 months of potential follow-up were selected from the Flatiron Health EHR-derived de-identified database (n = 172). Based on prior ICI exposure, pts were assigned to either the R+D post-ICI or the R+D post non-ICI [other] unmatched cohort. Study endpoints during R+D therapy included real-world (rw) objective response rate [rwORR], rw disease control rate [rwDCR], rw time to first response [rwTTFR], rw duration of response [rwDOR] & rw best response [rwBR]. Results: Overall, median age was 66.0 years and most pts were male (54.7%), white (70.3%), treated in the community (99.4%), had nonsquamous histology (79.7%), were stage IV at diagnosis (70.9%), had a low (≤ 1) Charlson comorbidity index (90.7%) & ECOG ≤ 1 (57.6%). Among tested pts, most were negative for EGFR (93.0%), ALK (94.9%) ROS1 (96.6%), or PD-L1 (75.0%). Baseline characteristics were similar between cohorts. Table shows significant differences in rwBR & rwDCR when stratified by cohort. Conclusions: Pts receiving R+D in the post-ICI setting had improved rwDCR compared to the R+D post-Other group, driven by a greater proportion of rwPR & a higher rate of rwSD as rwBR. The proportion of rwPD as rwBR was lower in R+D post-ICI pts. rwTR rates were generally similar to tumor response outcomes reported in REVEL. Understanding impact on OS is warranted given the increasing use of ICIs in earlier lines of therapy. [Table: see text]

e20727 Background: R+D is approved for use in pts with aNSCLC after Pt chemotherapy. With recent approvals, ICI can now be added to Pt chemotherapy (Pt + ICI) in 1L. This retrospective observational study provides an exploratory view of baseline characteristics and rw clinical effectiveness outcomes for pts receiving 2L R+D post 1L Pt + ICI. Methods: All adult pts treated with 2L R+D after 1L Pt + ICI therapy between 03/01/2015 and 06/30/2018, with ≥ 3 months follow up, were selected from the Flatiron Health EHR-derived de-identified database (n = 15). Rw clinical endpoints during R+D therapy included rw objective response rate (rwORR), rw disease control rate (rwDCR), rw best response, as well as Kaplan-Meier estimates of rw time to first response & rw duration of response. Results: Median age was 62 years, 10 pts (66.6%) were aged < 65 years, 11 (73.3%) were men, 3 (20.0%) had no history of smoking, 14 (93.3%) had non-squamous histology, 4 (26.7%) were EGFR positive, 3 (20.0%) were KRAS positive and 6 (85.7%) were PD-L1 negative. Of the 8 pts with a documented rw tumor response assessment, 3 (37.5%) had partial response (PR), 3 (37.5%) had stable disease (SD), & 2 (25.0%) had progressive disease as their rw best response. The rwORR (PR or complete response [CR]) & rwDCR (PR, CR, or SD) were 37.5% and 75.0%, respectively. Among responding pts, median time to first response was 2.2 months (95% CI, 1.3 - not reached [NR]) & median duration of response was 2.3 months (95% CI, 1.5 - NR). Patient numbers were too small (n = 15) and duration of follow-up was too short (3.4 months [IQR, 0.7 - 5.4]) to make robust estimation of overall survival or rw progression free survival. Conclusions: Data from this small patient cohort in US community practice are not conclusive and should be considered exploratory, but do show high rates of rw objective response and rw disease control rates during 2L R+D following 1L Pt + ICI. Data with larger sample sizes and additional follow-up are needed to better understand outcomes of R+D following the addition of ICI to 1L Pt chemotherapy regimens.

e20716 Background: RDP on initial therapy imposes significant clinical burden among pts with aNSCLC. This retrospective claims study provides estimates of the economic burden associated with RDP during subsequent therapy following RDP v non-RDP on platinum-based (Pt) therapy. Methods: Adult Medicare Advantage or commercially insured aNSCLC pts receiving a subsequent line of therapy (LOT) from 03/2015 to 08/2017 after initial Pt therapy were identified in the Optum Research Database and assigned to unmatched RDP & non-RDP cohorts based on Pt treatment duration (≤ 12 and > 12 weeks, respectively) as a surrogate. All-cause healthcare costs were inflation adjusted to 2017 US$ and computed as per patient per month (PPPM) during the subsequent LOT. Total costs were the sum of medical (inpatient, ambulatory, ER, and other costs) and outpatient pharmacy costs. Results: Patient characteristics were similar between RDP (n = 751) and non-RDP (n = 1,304) cohorts, with mean age of 68 years for the total study sample (n = 2,055). Overall, nivolumab was the most common subsequent regimen post Pt; 40% of the total study sample. While duration of subsequent LOTs was shorter for RDP pts (Kaplan-Meier median, 167 v 192 days and log rank test P = 0.03), mean systemic therapy drug costs were similar ($10,516 v $9,642, P = 0.14) during the LOT and PPPM total costs for RDP pts were $4,103 higher than those for non-RDP pts, driven by higher PPPM costs for inpatient stays and ambulatory visits (Table). Conclusions: This study sheds light on the significant economic burden of aNSCLC that rapidly progresses, and may inform management strategies to improve outcomes and lower downstream costs for RDP pts. Future research should continue to explore unmet needs for RDP pts, including underlying cost drivers, to provide context for the rapidly changing aNSCLC treatment landscape.[Table: see text]

Introduction This prospective observational study evaluated the effect of race on disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in patients with NSCLC treated with second-line pemetrexed. Patients and Methods Eligibility criteria included stage IIIB or IV NSCLC patients receiving single-agent pemetrexed for second-line therapy in routine clinical practice. Noninferiority was evaluated using logistic regression analysis of DCR, controlling for predefined covariates. Noninferiority was considered if the upper 95% confidence bound on the adjusted odds ratio (OR) for Caucasian vs. African-American individuals was less than 1.78, corresponding to a difference in proportion of 14% assuming Caucasian individuals to have a DCR of approximately 50%. The bound was chosen to be half of the anticipated difference between treatment and no second-line treatment. PFS and OS were estimated using the Kaplan–Meier method. Tools were used to measure functional status and symptom burden. Results The unadjusted DCR was 43.7% (117/268) for Caucasian and 45.0% (27/60) for African-American individuals (unadjusted OR, 0.95; 95% confidence interval [CI], 0.54-1.66). The adjusted OR in the final logistic regression model was 0.82 (95% CI, 0.43-1.58). This upper 95% confidence bound was within the prespecified acceptable bound of 1.78. Median PFS times (months) were 2.7 (95% CI, 2.4-3.4) for Caucasian and 3.0 (95% CI, 2.3-4.7) for African-American individuals (P = .91). Median OS times (months) were 6.7 (95% CI, 5.7-7.9) for Caucasian and 6.9 (95% CI, 4.5-8.9) for African-American individuals (P = .92). Baseline and functional status after baseline assessment and mean symptom burden did not differ substantially among races. Conclusion African-American race was not considered to be a significant predictor of disease control after second-line treatment with pemetrexed.

Background This was a post hoc analysis of patients with non-squamous histology from a phase III maintenance pemetrexed study in advanced non-small cell lung cancer (NSCLC). Patients and methods The six symptom items' [average symptom burden index (ASBI)] mean at baseline was calculated using the lung cancer symptom scale (LCSS). Low and high symptom burden (LSB, ASBI < 25; HSB, ASBI ≥ 25) and performance status (PS: 0, 1) subgroups were analyzed for treatment effect on progression-free survival (PFS) and overall survival (OS) using the Cox proportional hazard models adjusted for demographic/clinical factors. Results Significantly longer PFS and OS for pemetrexed versus placebo occurred in LSB patients [PFS: median 5.1 versus 2.4 months, hazard ratio (HR) 0.49, P < 0.0001; OS: median 17.5 versus 11.0 months, HR 0.63, P = 0.0012] and PS 0 patients (PFS: median 5.5 versus 1.7 months, HR 0.36, P < 0.0001; OS: median 17.7 versus 10.3 months, HR 0.54, P = 0.0019). Significantly longer PFS, but not OS, occurred in HSB patients (median 3.7 versus 2.8 months, HR 0.50, P = 0.0033) and PS 1 patients (median 4.4 versus 2.8 months, HR 0.60, P = 0.0002). Conclusions ASBI and PS are associated with survival for non-squamous NSCLC patients, suggesting that maintenance pemetrexed is useful for LSB or PS 0 patients following induction.

IntroductionIn a phase III, randomized, double-blind study (PARAMOUNT), maintenance pemetrexed demonstrated significant benefit in advanced non–small-cell lung cancer (NSCLC). We present safety, resource use, and quality of life (QoL) results.MethodsAfter four 21-day cycles of pemetrexed-cisplatin (N = 939), patients with advanced nonsquamous NSCLC, whose disease had not progressed and who had a performance status of 0/1, were randomized 2:1 (N = 539) to maintenance pemetrexed 500 mg/m2 plus best supportive care or placebo plus best supportive care every 21 days until disease progression or unacceptable toxicity. QoL was measured using the EuroQol 5-dimensional questionnaire (EQ-5D).ResultsFrequently reported grade 3 to 4 drug-related toxicities with maintenance pemetrexed versus placebo were anemia (4.5% versus 0.6%; p = 0.016), fatigue (4.2% versus 0.6%; p = 0.016), and neutropenia (3.6% versus 0.0%; p < 0.006). No significant differences in drug-related grade 3 to 5 toxicities were observed with long-term pemetrexed exposure (>6 cycles), except grade 3 to 4 neutropenia, which did not result in increased infections. Patients on maintenance pemetrexed required more transfusions (13.4% versus 5.0%; p = 0.003), granulocyte colony- or granulocyte-macrophage colony-stimulating factors (5.3% versus 0.0%; p

Small cell lung cancer (SCLC) is associated with poor prognosis due to its early metastatic potential and lack of improved outcomes with newer cytotoxic agents. Identifying factors associated with clinical outcomes can help clinicians determine which patients are more likely to benefit from therapy. Functional Assessment of Cancer Therapy (FACT) subscales and Eastern Cooperative Oncology Group performance status (ECOG PS) were retrospectively analyzed as prognostic factors for overall survival (OS) and progression-free survival (PFS) in patients with extensive-stage disease (ED)-SCLC.Using data from a Phase III trial of pemetrexed-carboplatin vs. etoposide-carboplatin, the effect of the prognostic factors on OS and PFS was analyzed via Cox models. The Kaplan-Meier method was used to estimate OS and PFS parameters for the prognostic subgroups (defined by baseline FACT scores and ECOG PS).Patients with higher baseline FACT-General (FACT-G) score (≥ median) had significantly higher OS (hazard ratio [HR]=0.62, P.0001) and PFS (HR=0.83, P=.032) compared with patients with lower FACT-G score (median). Similar results were observed for higher baseline physical well-being (PWB) and functional well-being (FWB) scores. For OS, there was a significant interaction between PS and FACT-PWB score (P=.005). In patients with PS=2 and higher FACT-PWB scores at baseline, a 48% reduction in the risk of death (P=.025) and nearly 3-month longer median OS were estimated.Higher baseline FACT-G, FACT-PWB, and FACT-FWB scores were found to be favorable prognostic factors for survival in ED-SCLC. Higher FACT-PWB scores at baseline predicted better survival for patients with poorer PS.

e21120Background: This review aimed to summarize the clinical utility (efficacy, safety, and quality of life) of ramucirumab compared to nintedanib, immune checkpoint inhibitors (ICIs), and chemoth...