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Uncommon epidermal growth factor receptor (EGFR) mutations have emerged as a therapeutic challenge in patients with EGFR mutant NSCLC. These mutations are a heterogenous group of aberrations in exons 18-21 and constitute almost 20% of all EGFR mutations. The most common of these are substitution mutations of G719X, L861Q, S768I, as well as exon 20 insertions and compound mutations. Currently, only, afatinib has been approved by regulatory agencies for the therapy of uncommon EGFR mutations. With the introduction of osimertinib, there has been interest in evaluating this agent for the therapy of uncommon mutations.

In this issue of the journal, Bar and colleagues present findings from  a nine-country multi-center retrospective study of patients with metastatic NSCLC with uncommon EGFR mutations excluding exon 20 insertions, treated with osimertinib as a first-line EGFR TKI (the UNICORN study). In this 60-patient study, which is the largest osimertinib cohort to date, the ORR was 61%, mPFS 9.5m, median duration of response 22.1m.  These results may indicate that osimertinib could be appropriate front-line treatment for patients with uncommon EGFR mutations. Importantly, the implications of this study in the context of current available data are critically reviewed in an excellent accompanying editorial by  Drs Lim and Tan. 

Because of strict eligibility criteria in most pivotal phase III trials, there is ongoing concern on the applicability of clinical trial findings to the general population. This has led to an increasing interest in post marketing “real world” data. Thus, building on the PACIFIC trial which established one year of consolidation durvalumab after definitive chemoradiotherapy for stage III unresectable NSCLC as a new standard-of-care,  the PACIFIC-R study aimed to assess the ‘real-world’ outcomes of consolidation durvalumab in an Expanded Access Program in Europe. This program enrolled 1399 patients from 11 countries. The study found that the results of PACIFIC R in terms of PFS is similar to that of PACIFIC. Median overall survival was not reached for PACFIC-R, but approximately 71.2% of patients were alive at 24 months. These findings and their relevance to current practice are discussed in an excellent editorial by Dr Jarushka Naidoo and her colleagues.

Thymic epithelial tumors are the most common malignancies of the anterior mediastinum, even though they are rare. Therapeutic options after progression on front-line platinum-based therapy are limited. PD(L)-1 inhibitors have been used but their use is hampered by a high incidence of immune-related adverse events. Because genetic alterations associated with the cell cycle, including pRB, p16 INK4A , and cyclin D1, are commonly observed in thymic epithelial tumors (TETs), the CDK4/6 inhibitor palbociclib was evaluated in TETs, in a phase II multicenter trial in South Korea. Dr. Jung and colleagues report the results of the trial in this issue of the journal, demonstrating promising efficacy. If confirmed in larger studies, a new therapeutic class will become available for this rare disease. These and other considerations are explored in an insightful accompanying editorial by Dr Artal-Cortes and colleagues

While this journal accepts manuscripts dealing with primary thoracic malignancies within the purview of thoracic surgeons, there are few meritorious manuscripts concerning esophageal cancer submitted for consideration of publication. We note that esophageal cancer is the sixth most common cause of cancer-related death worldwide. Thus we highlight a retrospective single institution study comparing transthoracic esophagectomy performed either by open or robotic approaches in order to evaluate whether there is a difference in sarcopenia, presented by Merboth and colleagues. The investigators found that there was a significantly lower incidence of sarcopenia with robot-assisted minimally invasive esophagectomy compared to open esophagectomy. Confirmation of these results in larger studies will cement the idea that minimally invasive surgical approaches may be superior to traditional open approaches not only in esophageal cancer, but also in a number of thoracic malignancies.

Alex A. Adjei, MD, PhD
Editor-in-Chief

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Figure 1 (A) One week after pembrolizumab administration, most fingers were cold and cyanotic from the distal interphalangeal joint to the fingertips, with gangrene in the right index finger. (B) Eight weeks after pembrolizumab administration, six fingers became gangrenous without improvement. More

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Journal of Thoracic Oncology

Cover Image - Journal of Thoracic Oncology, Volume 18, Issue 2

Journal of Thoracic Oncology (JTO), the official journal of the International Association for the Study of Lung Cancer, is the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. JTO emphasizes a multidisciplinary approach and includes original research reviews and opinion pieces. The audience includes epidemiologists, medical oncologists, radiation oncologists, thoracic surgeons, pulmonologists, radiologists, pathologists, nuclear medicine physicians, and research scientists with a special interest in thoracic oncology. The journal is interested in receiving manuscripts dealing with epidemiology, prevention, screening, early detection, staging, cure, and treatment of thoracic malignancies. More

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The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. More

Companion Journal

Cover Image - JTO Clinical and Research Reports, Volume 4, Issue 1

JTO Clinical and Research Reports is the official open access journal of the International Association for the Study of Lung Cancer. More

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