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Abstract Background In non-small cell lung cancer (NSCLC), interstitial hypertension is a barrier to chemotherapy delivery, and is mediated by platelet derived growth factor receptor (PDGFR). Antagonizing PDGFR with imatinib may improve intra-tumoral delivery of paclitaxel, increasing response rate (RR). Methods This single-stage, open-label phase II study evaluated pulse dose imatinib and weekly paclitaxel in elderly patients with advanced NSCLC. Eligible patients were aged ≥ 70 with untreated, stage IIIB-IV NSCLC and ECOG performance status 0-2. Primary endpoint was RR. Secondary endpoints included median progression free and overall survival (PFS, OS) and correlatives of PDGFR pathway activation. Baseline Charlson Comorbidity Index (CCI) and Vulnerable Elder Survey-13 (VES-13) were correlated with outcomes. Results Thirty-four patients with median age 75 enrolled. Eleven of 29 (38%) were frail by VES-13 score. Overall RR was 11/34 (32%; 95% CI 17%-51%), meeting the primary endpoint. Median PFS and OS were 3.6 and 7.3 months, respectively. High tumoral PDGF-B expression predicted inferior PFS. Frail patients by VES-13 had significantly worse median PFS (3.2 vs. 4.5 months; p=0.02) and OS (4.8 vs. 12 months; p=0.02) than non-frail. Conclusions The combination of imatinib and paclitaxel had encouraging activity as measured by the primary endpoint of RR. However, PFS and OS were typical for elderly patients treated with single agent chemotherapy and the regimen is not recommended for further study. Adjunct imatinib did not overcome the established association of tumoral PDGF-B expression with inferior PFS. VES-13 was a powerful predictor of poor survival outcomes. Frailty should be further studied as a predictor of non-benefit from chemotherapy. Trial Registration ClinicalTrials.gov NCT01011075

Purpose: We sought to examine the prognostic value of fluorodeoxyglucose-positron emission tomography (PET) imaging during chemoradiation for unresectable non-small cell lung cancer for survival and hypothesized that tumor PET response is correlated with peripheral T-cell function., Methods and Materials: Forty-five patients with American Joint Committee on Cancer version 7 stage IIB-IIIB non-small cell lung cancer enrolled in a phase II trial and received platinum-doublet chemotherapy concurrent with 6 weeks of radiation (NCT02773238). Fluorodeoxyglucose-PET was performed before treatment start and after 24 Gy of radiation (week 3). PET response status was prospectively defined by multifactorial radiologic interpretation. PET responders received 60 Gy in 30 fractions, while nonresponders received concomitant boosts to 74 Gy in 30 fractions. Peripheral blood was drawn synchronously with PET imaging, from which germline DNA sequencing, T-cell receptor sequencing, and plasma cytokine analysis were performed., Results: Median follow-up was 18.8 months, 1-year overall survival (OS) 82%, 1-year progression-free survival 53%, and 1-year locoregional control 88%. Higher midtreatment PET total lesion glycolysis was detrimental to OS (1 year 87% vs 63%, P < .001), progression-free survival (1 year 60% vs 26%, P  = .044), and locoregional control (1 year 94% vs 65%, P  = .012), even after adjustment for clinical/treatment factors. Twenty-nine of 45 patients (64%) were classified as PET responders based on a priori definition. Higher tumor programmed death-ligand 1 expression was correlated with response on PET ( P  = .017). Higher T-cell receptor richness and clone distribution slope were associated with improved OS ( P  = .018-0.035); clone distribution slope was correlated with PET response ( P  = .031)., Conclusions: Midchemoradiation PET imaging is prognostic for survival; PET response may be linked to tumor and peripheral T-cell biomarkers., (© 2021 The Authors.)

Objectives: To identify commonly prescribed first-, second-, and third-line chemotherapy regimens for persons with lung cancer and to evaluate the utilization patterns and costs of care associated with receiving these regimens., Study Design: Retrospective data analysis., Methods: Using health insurance claims from January 1, 2002, through December 31, 2006, patients with lung cancer were identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. An algorithm was developed to identify first-, second-, and third-line chemotherapy. Patients were stratified by the number of discrete regimens received or by their specific chemotherapy agent or combination of agents. Data were analyzed for up to 2 years from the date of the initial first-line regimen and for 1 year from the second and third lines. Patient costs were based on total reimbursements for each group during the observation period., Results: Of patients receiving first-line chemotherapy, 25% and 10% received second-line and third-line chemotherapy, respectively. Docetaxel, gefitinib, and erlotinib hydrochloride were the most commonly prescribed second-line regimens; gefitinib and docetaxel were the most commonly prescribed third-line regimens. The most commonly prescribed second- and third-line agents changed substantially over time. Total costs and costs per patient per month increased as the number of lines of chemotherapy prescribed increased., Conclusions: Second- and third-line chemotherapy is prescribed infrequently, and patterns of prescribing are changing over time. Direct medical care costs increase substantially with additional lines of therapy.