Lung cancer : journal of the International Association for the Study of Lung Cancer
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Immune checkpoint inhibitors are considered standard second-line treatment in advanced non-small cell lung cancer patients. This strategy has also become standard in first-line setting for a subgroup of patients with strongly positive PD-L1 tumors; therefore, PD-L1 status might be considered a new biomarker that deserves upfront testing. ⋯ However, some questions remain unanswered such as the best treatment strategy or the real upfront efficacy of these therapeutic strategies in the whole lung cancer population. In this review we summarize the main results in the first-line setting of recent phase III trials with immune checkpoint inhibitors in advanced non-small cell lung cancer patients.
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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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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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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.
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Multicenter Study Clinical Trial
Predictive factors for EGFR-tyrosine kinase inhibitor retreatment in patients with EGFR-mutated non-small-cell lung cancer - A multicenter retrospective SEQUENCE study.
Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations experiencing a response to EGFR-tyrosine kinase inhibitor (TKI) initially. We investigated EGFR-TKI retreatment in patients who had previously received EGFR-TKI followed by chemotherapy. ⋯ EGFR-TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR-mutated NSCLC patients after failure of first-line EGFR-TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR-TKI and in females with the exon 21 mutation.