Brain Metastases in Non–Small-Cell Lung Cancer

Up to 50% of patients with advanced non-small-cell lung cancer will develop brain metastases at some point during their illness. These metastases cause a substantial burden in morbidity and mortality, which has motivated research and technological innovation over the past 2 decades. Surgery, radiotherapy, and systemic therapies have each played a role in management, with the greatest changes associated with the popularization of stereotactic radiosurgery. In this review, the evidence behind each modality used in the management of brain metastases for non–small-cell lung cancer patients is examined, and recommendations regarding the current standards of care and areas of future research focus are provided.     

Advanced Non–Small-Cell Lung Cancer in the Elderly

Systemic chemotherapy provides improvement in both survival and quality of life for patients with advanced non–small-cell lung cancer (NSCLC). Elderly patients have more comorbidities and tend to tolerate more poorly aggressive chemotherapy and radiation therapy than younger individuals. Our purpose in this article is to summarize recent studies of single-agent chemotherapy and combination regimens with cytotoxic or targeted therapies in the management of elderly patients with advanced NSCLC. We have reviewed the available evidence in the literature to gauge the results of therapy for elderly patients with lung cancer. We found that single-agent chemotherapy remains the standard of care for nonselected elderly patients. Retrospective analyses suggest that the efficacy of platinum-based combination chemotherapy is similar in fit older and younger patients, with increased but acceptable toxicity for elderly patients. Therefore, the outcomes in the fit elderly mirror results observed in younger patients, although toxicity is generally greater.     

Crizotinib in the Treatment of Non–Small-Cell Lung Cancer

An anaplastic lymphoma kinase (ALK) translocation giving rise to activated ALK tyrosine kinase is present in approximately 5% of non–small-cell lung cancers (NSCLCs). Crizotinib is an oral tyrosine kinase inhibitor targeting ALK, met proto-oncogene, and c-ros oncogene 1 (ROS1). It was recently approved in several countries for the treatment of patients with advanced, ALK-rearranged NSCLC. In 2012, results from the first phase III trial showing superiority of crizotinib compared with standard chemotherapy in second-line treatment of ALK-positive NSCLC were presented. Furthermore, crizotinib was recently shown to be active in ROS1-rearranged NSCLC. Here, we give an overview of the molecular pathogenesis of ALK-rearranged NSCLC, the pharmacokinetic and pharmacodynamic properties of crizotinib, and clinical trials of crizotinib for ALK-rearranged NSCLC.     

Current Data with Pemetrexed in Non–Small-Cell Lung Cancer

Pemetrexed (Alimta®) is a novel multitargeted antifolate that inhibits 3 enzymes involved in folate metabolism and purine and pyrimidine synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent has broad antitumor activity in phase II trials in a wide variety of solid tumors. In non–small-cell lung cancer (NSCLC), single-agent activity has been documented in the first- and second-line settings. Promising activity has also been demonstrated when pemetrexed is combined with cisplatin and gemcitabine. A pivotal phase III study in mesothelioma has been presented, indicating the superiority of pemetrexed in combination with cisplatin versus cisplatin alone in this disease. Approval for pemetrexed in combination with cisplatin in advanced mesothelioma is expected within the next 12 months. This review discusses the activity of pemetrexed in NSCLC.     

Oxaliplatin in First-line Therapy for Advanced Non–Small-Cell Lung Cancer

Platinum doublets are the recommended standard first-line chemotherapy for stage IIIB/IV non–small-cell lung cancer (NSCLC). As efficacy outcomes associated with currently approved agents (cisplatin and carboplatin) are broadly similar, the decision about which platinum-based doublet to use is based on other factors such as toxicity. The goals for new platinum agents are to maintain and perhaps improve current efficacy and to improve toxicity. The aim of this article is to review the available clinical data from studies investigating the third-generation platinum analogue oxaliplatin in patients with advanced NSCLC. Information was obtained from the PubMed database and from recent presentations at national and international meetings. Oxaliplatin has been studied as monotherapy and in combination with a wide range of other chemotherapies (vinca alkaloids, taxanes, gemcitabine, and pemetrexed), mainly in phase II trials. Preliminary results from studies in which oxaliplatin-based doublets have been combined with targeted agents (eg, bevacizumab) are now available. In general, the clinical activity observed with oxaliplatin-based therapy is similar to that seen with other currently used platinum regimens, although outcomes vary between individual trials (response rates, 23%-48%; median progression-free survival, 2.7-7.3 months; median overall survival, 7.3-13.7 months). The toxicity profile of oxaliplatin, particularly when compared with cisplatin, makes it an alternative treatment, especially in patients unable to tolerate cisplatin. However, well-conducted randomized phase III trials will be needed to clarify which particular groups of patients with NSCLC may benefit from oxaliplatin-based therapy.     

Interdisciplinary Palliative Care Intervention in Metastatic Non–Small-Cell Lung Cancer

ObjectiveChallenges and barriers continue to hinder the integration of palliative care models into comprehensive, ambulatory oncology care. This article aims to describe how symptoms, distress, and quality of life (QOL) data from the usual care phase of a National Cancer Institute–supported Program Project informed the development of an interdisciplinary, tailored palliative care intervention for patients with metastatic non–small-cell lung cancer (NSCLC).MethodsPatients receiving usual care for metastatic NSCLC were recruited into this prospective longitudinal study over a 1-year period. A total of 130 patients with stage IV NSCLC were accrued, and 114 patients had evaluable data. Research nurses assisted patients in completing the clinical section of the data forms, and patients completed surveys and self-reports at baseline and 6, 12, and 24 weeks.ResultsPatients ranged in age from 40 to 84 years, and 61% were Caucasian non-Hispanic. Sixty-six former (N = 59) and current smokers had an average of 38 pack-year history of smoking. The Karnofsky Performance Status, Instrumental Activities of Daily Living, and Cognitive scores deteriorated significantly (P = .001, .009, and .042, respectively). Social Activity was stable, whereas Social Support increased significantly. Overall symptom distress score and Total symptom score both significantly increased at 24 weeks (P = .003 and .017, respectively). Physical Well-Being decreased significantly (P = .036), whereas the Functional Assessment of Cancer Therapy-Lung, Functional Assessment of Chronic Illness Therapy-Spirituality Subscale, and Distress scores remained statistically stable over time.ConclusionsPatients with metastatic NSCLC continue to experience high symptom burden and diminished physical well-being over time while receiving cancer treatments. An interdisciplinary palliative care intervention is currently being tested to improve symptom burden and overall QOL.     

A Reasonable Definition of Oligo-Recurrence in Non–Small-Cell Lung Cancer

BackgroundThe concept of oligo-recurrence in non–small-cell lung cancer (NSCLC) has been suggested to describe the possibility of achieving long-term survival or even cure with local therapy for recurrence despite having recurrent disease. Oligo-recurrence involves a limited number of metachronous recurrences that can be treated with local therapy. However, the number of recurrences that constitutes an oligo-recurrence has varied among studies and remains to be defined. The aim of this study was to elucidate the number of recurrences that constitutes an oligo-recurrence in NSCLC.Patients and MethodsWe retrospectively reviewed 577 patients with NSCLC who had underwent complete resection and developed recurrence between 1990 and 2009, and these patients were evaluated.Patients were categorized according to the number of recurrences, and postrecurrence survival (PRS) was compared between groups.ResultsAltogether, 270 patients underwent local therapy for all recurrent lesions. In these patients, sex (female), histological type (adenocarcinoma), gene mutation status, recurrence-free interval <1 year, and presence of 1 or 2 recurrences were factors associated with prolonged PRS. Additionally, all patients who maintained a cancer-free status for at least 5 years after treatment for recurrence and were considered possibly cured, had 1 or 2 recurrences.ConclusionAmong patients receiving radical local therapy, the PRS was particularly longer among those with 1 or 2 recurrences, and these patients were able to aim for postrecurrence cure. Thus, a reasonable threshold to define oligo-recurrence in NSCLC is 1 or 2 recurrences that can be treated with local therapy.     

Immunohistochemistry for EGFR Mutation Detection in Non–Small-Cell Lung Cancer

Introduction

The sensitivity and specificity of immunohistochemistry (IHC) was compared with the standard polymerase chain reaction (PCR)-based method for detecting common activating epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC). Additionally, we evaluated predictive value of IHC EGFR mutation–positive status for EGFR tyrosine kinase inhibitor (TKI) treatment outcome and estimated cost-effectiveness for the upfront IHC testing.

Molecularly Targeted Therapies in Locally Advanced Non–Small-Cell Lung Cancer

Approximately a third of the patients with non-small cell lung cancer (NSCLC) present with locally advanced disease not amenable to curative resection. Concurrent chemoradiation is currently the treatment of choice for these patients. Outcomes in patients with locally advanced NSCLC treated with concurrent chemoradiation are modest at best. No significant progress has been made over the past decade in this subset of patients with NSCLC. Several trials have examined the role of molecular targeted therapies in this setting. We review the results of these trials and present the outline of a proposed prospective clinical trial to evaluate targeted drugs in molecularly selected group of patients with locally advanced NSCLC.     

Biomarkers of Immune Checkpoint Inhibitors in Non–Small Cell Lung Cancer: Beyond PD-L1

Immunotherapy has markedly improved the survival rate of patients with non–small cell lung cancer (NSCLC) and has introduced a new era in lung cancer treatment. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Thus, it is crucial to identify potential biomarkers suitable for screening the population that may benefit from immunotherapy. Based on the current clinical trials, the aim of the present study was to review the biomarkers for immune checkpoint inhibition that may have the potential to predict the response to immunotherapy in patients with lung cancer. A non-systematic literature review was done. We searched for eligible randomized controlled trials (RCTs) from PubMed, Embase, and the Cochrane Central Register of Controlled Trials from January 2015 to January 2021. The keywords included biomarkers, immunotherapy, immune checkpoint inhibition, programmed death ligand 1 (PD-L1), and non–small cell lung cancer. Additional biomarkers beyond PD-L1 that have been shown to have predictive capacity include tumor mutational burden, microsatellite instability, lung immune prognostic index, gut microbiome, and certain alterations in genes (eg, STK11 deletion, LKB1 kinase mutation, MDM2/4 amplification) that confer immunoresistance. The biomarkers reviewed in this article could help us better select the appropriate immunotherapy treatment for patients with NSCLC.