Lung cancer : journal of the International Association for the Study of Lung Cancer
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Lung cancer is one of the leading causes of cancer death in men and women and treatment outcome continues to lag behind other common cancer types. A subset of lung adenocarcinoma patients exhibit a somatic mutation in EGFR or an ALK rearrangement. In these patients, targeted TKI therapy results in higher response rates, improved PFS and reduced side effects compared with platinum-based chemotherapy. ⋯ Radical local treatment to all oligoprogressive lesions is thought to eradicate the de-differentiated clones and restore overall sensitivity of the metastatic disease. Retrospective studies suggest that aggressive local treatment using stereotactic body radiotherapy (SBRT), surgery or others can be used to eradicate TKI-resistant subpopulations enabling prolonged TKI treatment "beyond progression", which may lead to increased PFS and overall survival. This review focuses on the biological background of resistance development, systemic and local treatment options with a focus on SBRT, as well as challenges in defining the state of OPD and current clinical studies in oligoprogressive oncogene addicted NSCLC.
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Development of the acquired ALK G1202R solvent front mutation and small cell lung cancer (SCLC) transformation have both been independently reported as resistance mechanisms to ALK inhibitors in ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients but have not been reported in the same patient. Here we report an ALK+ NSCLC patient who had disease progression after ceritinib and then alectinib where an ALK G1202R mutation was detected on circulating tumor (ct) DNA prior to enrollment onto a trial of another next generation ALK inhibitor, lorlatinib. The patient's central nervous system (CNS) metastases responded to lorlatinib together with clearance of ALK G1202R mutation by repeat ctDNA assay. ⋯ The patient never received crizotinib. This case illustrates that multiple/compound resistance mechanisms to ALK inhibitors can occur and provide supporting information that loss of p53 and Rb1 are important in SCLC transformation. If clinically feasible, tissue-based re-biopsy allowing histological examination and CGP remains the gold standard to assess resistance mechanism(s) and to direct subsequent rational clinical care.
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Thoracic radiotherapy plays an important role in the treatment of limited disease SCLC. Best results are obtained with twice daily (BID) radiotherapy, starting early and given concurrently with chemotherapy. ⋯ There was no statistically significant difference in survival between the two arms. Although the publication of the study is still awaited, this editorial puts the available data in perspective and draws some important conclusions.
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Observational Study
What factors do patients consider most important in making lung cancer screening decisions? Findings from a demonstration project conducted in the Veterans Health Administration.
The National Lung Screening Trial recently reported that annual low-dose computed tomography screening is associated with decreased lung cancer mortality in high-risk smokers. This study sought to identify the factors patients consider important in making lung cancer screening (LCS) decisions, and explore variations by patient characteristics and LCS participation. ⋯ Decision tools influence Veterans' perceptions about LCS decision-making factors. As the factors important to LCS decision making vary by patient characteristics, targeted materials for specific subgroups may be warranted. Attention should be paid to how LCS incidental findings are communicated.
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The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC. ⋯ BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy.