Treatment Rationale and Design for J-SONIC: A Randomized Study of Carboplatin Plus Nab-paclitaxel With or Without Nintedanib for Advanced Non–Small-cell Lung Cancer With Idiopathic Pulmonary Fibrosis

We describe the treatment rationale and procedure for a randomized study (J-SONIC; University Hospital Medical Information Network Clinical Trials Registry identification no., UMIN000026799) of carboplatin plus nanoparticle albumin-bound paclitaxel (nab-paclitaxel) with or without nintedanib for patients with advanced non–small cell lung cancer (NSCLC) and idiopathic pulmonary fibrosis (IPF). The study was designed to examine the efficacy and safety of nintedanib administered with carboplatin plus nab-paclitaxel versus carboplatin plus nab-paclitaxel alone in chemotherapy-naive patients with advanced NSCLC associated with IPF. Eligible patients (enrollment target, n = 170) will be randomized at a 1:1 ratio to receive 4 cycles of carboplatin (area under the curve, 6 on day 1) plus nab-paclitaxel (100 mg/m² on days 1, 8, and 15) administered every 3 weeks either without (arm A) or with (arm B) nintedanib (150 mg twice daily), to be followed in arm B by single-agent administration of nintedanib (150 mg twice daily). The present trial is the first randomized controlled study for the treatment of NSCLC associated with IPF. The goal of the study is to demonstrate that nintedanib combined with carboplatin plus nab-paclitaxel prolongs the interval to acute exacerbation of IPF compared with carboplatin plus nab-paclitaxel alone.     

Combination Therapy of Radiotherapy and Anti-PD-1/PD-L1 Treatment in Non–Small-cell Lung Cancer: A Mini-review

Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non–small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade. In the clinical setting, patients receiving radiotherapy before anti-PD-1 treatment have had a significantly better prognosis than those who have not undergone radiotherapy. In the present report, we reviewed previous studies of the combination of radiotherapy and anti-PD-1/PD-L1 treatment for NSCLC. In addition, we report our case of a patient whose PD-L1 expression gradually increased in brain metastases from NSCLC after repeated radiotherapy. In the perspectives portion, we focused on the questions of how to integrate radiotherapy into anti-PD-1/PD-L1 agent regimens and described several ongoing clinical trials.     

Lung Toxicity in Non–Small-Cell Lung Cancer Patients Exposed to ALK Inhibitors: Report of a Peculiar Case and Systematic Review of the Literature

Lung toxicity is a potential fatal effect involving non–small-cell lung cancer (NSCLC) patients exposed to tyrosine kinase inhibitors (TKIs). Moving from our experience regarding a patient who developed lung toxicity while receiving 2 different anaplastic lymphoma kinase (ALK)-TKIs, we performed a systematic review to assess the epidemiologic magnitude and the clinical significance of such toxicity in NSCLC patients treated with ALK-TKIs. Studies were identified using MEDLINE and additional sources (European Society for Medical Oncology, American Society of Clinical Oncology, and World Conference on Lung Cancer abstracts) in agreement with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane guidelines. Lung toxicity was reported in 105 of 4943 NSCLC patients (2.1%). Crizotinib was responsible for pulmonary adverse events (AEs) in 1.8% of exposed patients (49 of 2706). With the limit of a lower number of treated patients (n = 359), brigatinib resulted as the most frequently involved in lung toxicity (7%; n = 25). Pulmonary AEs during therapy with ceritinib, alectinib, and lorlatinib occurred in 1.1%, 2.6%, and 1.8% of the patients, respectively. Sixty-five percent of cases accounted for Grade 3 or 4 events, with a mortality rate of 9%. Radiological patterns of pneumonia were reported in 25 patients, whereas imaging evocative of interstitial lung disease in 37. Overall, 26 of 105 patients (25%) permanently discontinued treatment because of lung toxicity. Lung toxicity is a rare albeit potentially severe side effect in NSCLC patients receiving ALK-TKIs, apparently more frequent with brigatinib. Its early recognition and treatment are crucial for the best outcome of this subgroup of patients, whose overall prognosis is being improved by the availability of several targeted agents.     

Utility of Liquid Biopsy by Improved PNA-LNA PCR Clamp Method for Detecting EGFR Mutation at Initial Diagnosis of Non–Small-Cell Lung Cancer: Observational Study of 190 Consecutive Cases in Clinical Practice

Background

The clinical benefit of liquid biopsy for unselected patients at initial diagnosis has thus far been unclear. We aimed to evaluate the utility of liquid biopsy at initial diagnosis, as well as the efficacy of epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR-TKI) based on liquid biopsy results in clinical practice, using the improved peptide nucleic acid–locked nucleic acid (PNA-LNA) PCR clamp method.

Impact of Clinicopathologic Features on the Efficacy of PD-1/PD-L1 Inhibitors in Patients With Previously Treated Non–small-cell Lung Cancer

Background

The current study aimed to comprehensively investigate the impact of various clinicopathologic features on the efficacy of programmed cell death-1 (PD-1) and ligand (PD-L1) inhibitors in patients with previously treated non–small-cell lung cancer (NSCLC).

Practice Patterns and Outcomes in Elderly Stage I Non–Small-cell Lung Cancer: A 2004 to 2012 SEER Analysis

Background

We reviewed the population-based treatment patterns and outcomes for elderly patients with stage I non–small-cell lung cancer (NSCLC) treated from 2004 to 2012.

Treatment Patterns and Clinical Outcomes Among Metastatic Non–Small-Cell Lung Cancer Patients Treated in the Community Practice Setting

Introduction

Multiple therapeutic options now exist for metastatic non–small-cell lung cancer (mNSCLC). In this study we evaluated treatment patterns and outcomes in mNSCLC patients who received first-line (1L), second-line (2L), and third-line (3L) therapy.

Clinical Application of Genomic Profiling With Circulating Tumor DNA for Management of Advanced Non–Small-cell Lung Cancer in Asia

Background

Genomic profiling of cell-free circulating tumor DNA (ctDNA) is a potential alternative to repeat invasive biopsy in patients with advanced cancer. We report the first real-world cohort of comprehensive genomic assessments of patients with non–small-cell lung cancer (NSCLC) in a Chinese population.

A Randomized Phase III Study Comparing Carboplatin With Nab-Paclitaxel Versus Docetaxel for Elderly Patients With Squamous-Cell Lung Cancer: Study Protocol

Background

Treatment with carboplatin (CBDCA) with weekly paclitaxel (PTX) has shown survival benefits compared with vinorelbine or gemcitabine in elderly patients with non-small-cell carcinoma (NSCLC). Docetaxel (DOC), however, remains a standard treatment in NSCLC. The 130-nm albumin-bound formulation of PTX (nab-PTX) has shown activity in NSCLC. Treatment with CBDCA with weekly nab-PTX showed significantly higher efficacy than CBDCA with PTX in patients with squamous histology and significantly increased overall survival (OS) in patients aged 70 years and older.

Comparing Outcomes of Patients With Early-Stage Non–Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Frailty Status

Introduction

Frailty of surgical patients has been associated with worse outcomes. There is limited literature discussing frailty in patients with lung cancer treated with stereotactic body radiotherapy (SBRT). This study assesses the relationship between frailty and overall survival (OS), tumor control, and toxicity in patients with early-stage non–small-cell lung cancer (NSCLC) treated with SBRT.