Lung cancer remains the leading cause of cancer death world-wide. This is in part due patients presenting late with disseminated disease and despite recent advances, a limited therapeutic landscape... Despite these advances there remains a significant unmet clinical need with much research needed to elucidate the optimal treatment paradigm to improve response rates, mortality and quality of life for patients with advanced NSCLC. READ ARTICLE

Encyclopedia of Respiratory Medicine (Second Edition) DOI:10.1016/B978-0-08-102723-3.00265-1

Authors: Alice Davies, Martin Forster

Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial

Introduction: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ NSCLC. Methods: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into {less than or equal to}median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses. Results: Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all p<0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the {less than or equal to}median BEP (alectinib adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI): 1.07-3.89], p=0.0305; crizotinib adjusted HR 1.83 [95% CI: 1.11-3.00], p=0.0169). Median progression-free survival was longer with alectinib than crizotinib in both {less than or equal to}median and >median BEPs (p<0.0001). Overall survival data remain immature; survival probability was lower in the >median versus {less than or equal to}median BEP in both treatment arms (alectinib HR 2.52 [95% CI: 1.08-5.88], p=0.0333; crizotinib HR 2.63 [95% CI: 1.27-5.47], p=0.0096). Conclusion: These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding. READ ARTICLE

Clinical Cancer Research DOI:10.1158/1078-0432.CCR-21-2840

Authors: Rafal Dziadziuszko, Solange Peters, Tony Mok, D. Ross. Camidge, Shirish M. Gadgeel, Sai-Hong Ignatius. Ou, Krzysztof Konopa, Johannes Noé, Malgorzata Nowicka, Walter Bordogna, Peter N. Morcos, Vlatka Smoljanovic, Alice T. Shaw

Clinical TrialsKirk SmithFebruary 23, 2022Chemotherapy, targeted therapy, imaging, chest, lung cancer

Post-chemotherapy and targeted therapy imaging of the chest in lung cancer

Non-small-cell lung cancer (NSCLC) is frequently diagnosed when it is not amenable to local therapies; therefore, systemic agents are the mainstay of therapy for many patients. In recent years, treatment of advanced NSCLC has evolved from a general approach primarily involving chemotherapy to a more personalised strategy in which biomarkers such as the presence of genomic tumour aberrations and the expression of immune proteins such as programmed death-ligand 1 (PD-L1), in combination with other elements of clinical information such as histology and clinical stage, guide management. For instance, pathways resulting in uncontrolled growth and proliferation of tumour cells due to epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements may be targeted by tyrosine kinase inhibitors (TKIs). In this article, we review the current state of medical oncology, imaging characteristics of mutations, pitfalls in response assessments and the imaging of complications. READ ARTICLE

Clinical Radiology DOI:10.1016/j.crad.2021.08.001

Authors: B. W. Carter, M. Altan, G. S. Shroff, M. T. Truong, I. Vlahos

EditorialKirk SmithJanuary 1, 2022Chemotherapy, targeted therapy, imaging, chest, lung cancer

Treatment of anaplastic lymphoma kinase-positive lung adenocarcinoma with pemetrexed and carboplatin after crizotinib failure and significant liver dysfunction; a case report

Tyrosine kinase inhibitors are the first-line treatment for Anaplastic Lymphoma Kinase-positive lung adenocarcinomas. However, chemotherapy is still an option in patients who are unresponsive or intolerant of tyrosine kinase inhibitors. There is a high likelihood of brain metastasis in patient with lung adenocarcinomas with Anaplastic Lymphoma Kinase rearrangement. Surveillance brain imaging may have a role in clinical follow up. Brigatinib and lorlatinib are two tyrosine kinase inhibitors with excellent intracranial penetrance. READ ARTICLE

Cancer Treatment and Research Communications DOI:10.1016/j.ctarc.2020.100291

Authors: Oranus Mohammadi, Kayla Haines, Mohammad Jahanzeb,

Clinical Utility of Targeted Sequencing in Lung Cancer: Experience From an Autonomous Swedish Health Care Center

Objectives: Mutation analysis by massive parallel sequencing (MPS) is routinely performed in the clinical management of lung cancer in Sweden. We describe the clinical and mutational profiles of lung cancer patients subjected to the first 1.5 years of treatment predictive MPS testing in an autonomous regional health care region... Conclusion: Although the increasing importance of MPS as a predictor of response to targeted therapies is indisputable, its role in prognostics or as a predictor of clinical course in nontargetable advanced stage lung cancer requires further investigation. READ ARTICLE

JTO Clinical and Research Reports DOI:10.1016/j.jtocrr.2020.100013

Authors: Sofi Isaksson, Bassam Hazem, Mats Jönsson, Christel Reuterswärd, Anna Karlsson, Håkan Griph, Jens Engleson, Gudrun Oskarsdottir, Ronny Öhman, Karolina, Holm, Frida Rosengren, Karin Annersten, Göran Jönsson, Åke Borg, Anders Edsjö, Per Levéen, Hans Brunnström, Kajsa Ericson Lindquist, …Maria Planck

$Efficacy of Platinum/Pemetrexed Combination Chemotherapy in ALK-Positive NSCLC Refractory to Second-Generation ALK Inhibitors$

Efficacy of Platinum/Pemetrexed Combination Chemotherapy in ALK-Positive NSCLC Refractory to Second-Generation ALK Inhibitors

This was a retrospective study performed at three institutions. Patients were eligible if they had advanced ALK-positive NSCLC refractory to one or more second-generation ALK TKI(s) and had received platinum/pemetrexed-based chemotherapy. Among 58 patients eligible for this study, 37 had scans evaluable for response with measurable disease at baseline. The confirmed objective response rate to platinum/pemetrexed-based chemotherapy was 29.7% (11 of 37 patients; 95% confidence interval [CI]: 15.9% – 47.0%), with median duration of response of 6.4 months (95% CI: 1.6 months – not reached). The median progression-free survival for the entire cohort was 4.3 months (95% CI: 2.9 – 5.8 months). Progression-free survival was longer in patients who received platinum/pemetrexed in combination with an ALK TKI compared to those who received platinum/pemetrexed alone (6.8 months vs. 3.2 months, respectively; hazard ratio ¼ 0.33; p ¼ 0.025). Platinum/pemetrexed-based chemotherapy shows modest efficacy in ALK-positive NSCLC after failure of second-generation ALK TKIs. The activity may be higher if administered with an ALK TKI, suggesting a potential role for continued ALK inhibition. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2019.10.014

Authors: Jessica J. Lin, Adam J. Schoenfeld, Viola W. Zhu, Beow Y. Yeap, ScD, Emily Chin, BA, Marguerite Rooney, BA, Andrew J. Plodkowski, Subba R. Digumarthy, Ibiayi Dagogo-Jack, Justin F. Gainor, Sai-Hong Ignatius Ou, Gregory J. Riely, Alice T. Shaw

Real-World OutcomesKirk SmithOctober 12, 2019Chemotherapy, Efficacy, ALK, non-small cell lung cancer (NSCLC)