“My Patient Was Diagnosed With Nontargetable Advanced Non–Small Cell Lung Cancer. What Now?” Diagnosis and Initial Treatment Options for Newly Diagnosed Patients With Advanced NSCLC

Author(s):  
Melissa Johnson ◽  
Nathan A. Pennell ◽  
Hossein Borghaei

Although lung cancer remains the leading cause of cancer-related mortality in the United States and worldwide, the rate at which Americans are dying from lung cancer is declining. Improving survival can be explained, in large part, by a growing understanding of the heterogeneous biology of non–small cell lung cancer (NSCLC) as well as recent successes of novel therapeutic strategies more effective and tolerable than platinum-based chemotherapy. We now recognize distinct subtypes of NSCLC, defined by molecular profiling and immunohistochemistry, with different treatment algorithms, including targeted small molecular inhibitors and immunotherapy for each. Both biomarker selection and preferred frontline strategies continue to evolve rapidly, making it difficult for many practitioners to keep up. In this review, we will first describe the recommended initial workup for a patient with advanced or metastatic NSCLC in 2018; next, we present an algorithm to aid oncologists in the selection of the most appropriate therapy for treatment-naive patients with NSCLC, and finally, we offer a look into future treatment options through a discussion of ongoing clinical trials.

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Sherif Ahmed Abdelwahab ◽  
Dina Ahmed Salem ◽  
Caroline Magued Elmaraghi ◽  
Alaa Naguib Mohammed Hassan

Abstract Background Lung cancer represents the top cause of death and the most common cancer worldwide. In the United States, lung cancer is the second most common cancer accounts for 12.9% of new cancer diagnoses and 27.4 of all cancer deaths. Non small cell lung cancer (NSCLC) represents up to 80% of all lung cancers which divided into two major types: squamous cell carcinoma (SCC) and nonsquamous cell carcinoma (NSCC, including adenocarcinoma, large-cell carcinoma, and other subtypes). Aim of the Work To assess the correlation between CEA (carcinoembryonic antigen) levels and response to platinum-based chemotherapy assessed by RECIST criteria of advanced non-small cell lung cancer patients. Patients and Methods This is a prospective study conducted between November 2018 and July 2019, 30 consecutive patients with advanced NSCLC previously treated with at least one line of chemotherapy were prospectively enrolled in thoracic malignancies department in Ain-Shams university hospital and Ismailia Teaching Oncology Hospital. The study was approved by the ethics committee at the faculty of medicine, Ain Shams University. Results In our study we evaluated response by CTs according to RECIST criteria and considered patients with clinical response (PR and SD) as responders and patients with PD as non-responders. Conclusion Our study found correlation between CEA and radiological response and patients with CEA reduction equal or more than 18.5% have objective response to treatment with Sensitivity and specificity 66.67% and 85.71% respectively.


2010 ◽  
Vol 8 (7) ◽  
pp. 822-832 ◽  
Author(s):  
Charu Aggarwal ◽  
Neeta Somaiah ◽  
George R. Simon

Lung cancer is the leading cause of cancer-related mortality in the United States. Non–small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients with NSCLC present with locoregionally advanced or metastatic disease, for which response rates and median overall survival remain poor. Platinum-based chemotherapy is the mainstay of treatment for NSCLC in both adjuvant and metastatic disease. Personalized chemotherapy and targeted biologic therapy based on a tumor's histologic and molecular profile have already shown promise in optimizing efficacy. Various markers are currently being investigated for their ability to guide treatment decision-making and management. This article describes these predictive and prognostic markers and details their current role, benefit, and potential future use in the management of patients with NSCLC.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Katrina Kildey ◽  
Neha S. Gandhi ◽  
Katherine B. Sahin ◽  
Esha T. Shah ◽  
Eric Boittier ◽  
...  

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.


2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).


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