PD-L1 testing and clinical management of newly diagnosed metastatic non-small cell lung cancer in Spain: MOREL study

Aim: To describe the clinical management and PD-L1 testing of patients with newly diagnosed stage IV non-small cell lung cancer (NSCLC) without driver mutations in Spain. Methods: Multicenter, retrospective study. Results: Among 297 evaluated patients, 89.2% received systemic treatment for stage IV disease, of whom 53.6% received platinum doublet therapy, 26.8% immunotherapy as monotherapy and 14.7% immunotherapy + chemotherapy, with 9.4% receiving treatment as part of a clinical trial. Treatment was initiated 1 month after histological diagnosis, with PD-L1 test results available in most cases (92.6%). PD-L1 testing was performed in 287 patients, 95.1% by in-house tests, mostly with the 22C3 pharmDx assay. The factor most strongly associated with treatment selection was, as expected, the expression of PD-L1. Conclusion: PD-L1 testing is implemented in clinical practice and seems to guide treatment decisions in patients with NSCLC in Spain.

Lymphadenopathy and granulomas: benignancy of malignancy and differential diagnosis with endobronchial ultrasound-transbronchial needle biopsy 19G needle fine-needle aspiration biopsy

Endobronchial ultrasound (EBUS) is a very useful tool for the diagnosis of lymphadenopathy of the mediastinum. Nowadays, EBUS can substitute video-assisted thoracic surgery when a 19G needle is used. Several studies have provided data for efficient diagnosis not only for lung cancer, but for also sarcoidosis, tuberculosis and lymphoma. We present five cases of EBUS-transbronchial needle biopsy 19G needle used for the diagnosis of mediastinum lymphadenopathy. We present not only the pathological diagnosis, but also the steps for the differential clinical and pathological differential diagnosis for sarcoidosis, tuberculosis, cancer metastasis, respiratory infection and lymphoma.

HER3 expression and MEK activation in non-small-cell lung carcinoma

Aim: We explore HER3 expression in lung adenocarcinoma (adeno-NSCLC) and identify potential mechanisms of HER3 expression. Materials & methods: Tumor samples from 45 patients with adeno-NSCLC were analyzed. HER3 and HER2 expression were identified using immunohistochemistry and bioinformatic interrogation of The Cancer Genome Atlas (TCGA). Results: HER3 was highly expressed in 42.2% of cases. ERBB3 copy number did not account for HER3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a surrogate of functional signaling) did not correlate with HER3 ligands. ERBB3 RNA expression levels were significantly correlated with MEK activity after adjusting for EGFR expression. Conclusion: HER3 expression is common and is a potential therapeutic target by virtue of frequent overexpression and functional downstream signaling.

A comparative study of immunotherapy as second-line treatment and beyond in patients with advanced non-small-cell lung carcinoma

Background: Immunotherapy has demonstrated an improved overall survival (OS) and progression-free survival (PFS) as second-line treatment and subsequent lines compared with chemotherapy. Materials and methods: This was a retrospective review among eight medical centers comprising 100 patients with a confirmed diagnosis of non-small-cell lung carcinoma, in their second-line treatment or beyond with immune checkpoints inhibitors treatment. The current study aimed to analyze effectiveness of immunotherapy in second-line treatment or further in the Mexican population, using PFS rate, OS rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. Results: In total, 100 patients met the criteria for enrollment in the current study. From the total study population, 49 patients (49.0%) were male and 51 (51.0%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the study. A total of 61 patients (61.0%) had partial response; 11 (11.0%) stable disease; 2 (2.0%), complete response, 4 (4.0%), progression; and 22 (22.0%) were nonevaluable. We found a median PFS of 4 months (95% CI: 3.2–4.7 months) and an OS of 9 months (95% CI: 7.2–10.7 months). Conclusion: The response to immunotherapy is similar, with an improvement in OS and PFS, independent of which drug is used. Patients using nivolumab had a better survival, although that was not statistically significant.

Efficacy and safety of tyrosine kinase inhibitors in advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutation: a network meta-analysis

Aim: To compare the efficacy and safety of tyrosine kinase inhibitors (TKIs) as first-line treatment in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with positive EGFR mutation. Materials & methods: Following a systematic literature review until December 2019, we conducted a random-effects pairwise and network meta-analyses (NMA). We ranked treatments for efficacy and safety based on the surface under the cumulative ranking curve (SUCRA). Results: Tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) improved survival outcomes with fewer grade 3 or higher adverse events compared to chemotherapy. Overall survival results suggest that osimertinib has the highest probability of being the most efficacious (SUCRA, 79.9%), followed by dacomitinib (SUCRA, 75.8%). Adverse events results suggest that osimertinib (SUCRA, 84.3%) and gefitinib (SUCRA, 78.9%) has the highest probability of being the safest. Conclusion: In this NMA, we found that osimertinib is the most efficacious and safest EGFR-TKI. These results may guide clinicians in choosing the most appropriate treatment option among EGFR-TKIs for their patient’s individual clinical characteristics.

Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform

Aim: Evaluate real-world patient preferences, experiences and outcomes (health-related quality of life [HRQoL]) from patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) utilizing the ALKConnect Patient Insight Network. Patients & methods: Demographics, disease history/status/treatment, patient preferences and HRQoL (MD Anderson Symptom Inventory lung cancer module, reported as symptom severity and interference) were evaluated for US adults with ALK+ NSCLC. Results: Among 104 patients (median age: 53.0 years, 67.3% female, 40.0% employed), HRQoL and 3-month delay in disease progression were important treatment attributes. Burdensome symptoms included fatigue and disturbed sleep. Symptoms interfered most with work and day-to-day activity. Higher HRQoL was associated with ALK tyrosine kinase inhibitor (TKI) treatment and employment. Conclusion: ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC.

Treatment and outcomes for early non-small-cell lung cancer: a retrospective analysis of a Portuguese hospital database

Aim: This observational study evaluated treatment patterns and survival for patients with stage I–IIIA non-small-cell lung cancer (NSCLC). Materials & methods: Adults newly diagnosed with NSCLC in 2012–2016 at IPO-Porto hospital were included. Treatment data were available for patients diagnosed in 2015–2016. Results: 495 patients were included (median age: 67 years). The most common treatments were surgery alone or with another therapy (stage I: 66%) and systemic anticancer therapy plus radiotherapy (stage II: 54%; stage IIIA: 59%). One-year OS (95% CI) for patients with stage I, II and IIIA NSCLC (diagnosed 2012–2016) were 92% (88–96), 71% (62–82) and 69% (63–75), respectively; one-year OS (95% CI) for treated patients with stage I–II or stage IIIA NSCLC (diagnosed 2015–2016) were 89% (81–97) and 86% (75–98) for non-squamous cell and 76% (60–95) and 49% (34–70) for squamous cell NSCLC. Conclusion: Treatment advances are strongly needed for stage I–IIIA NSCLC, especially for patients with squamous cell histology.

Current clinical trials and patent update on lung cancer: a retrospective review

Several clinical trials using different interventions are currently being sponsored to combat lung cancer at its different stages. The purpose of this study was to provide a portfolio of those trials. All active, open and recruiting clinical trials registered at ClinicalTrials.gov up to March 2018 were included. Information related to 6092 registered lung cancer trials was downloaded. Phase II trials were in the majority, comprising nearly 48.7% of total clinical trials with industry the major sponsor (41.3%) followed by NIH (12.3%). Multicenter studies were the norm accounting for 47.9% and the main study location was the USA (50.9%). Common interventions were radiation (26%), surgery (22%) and EGFR inhibitors (17%). Patent information includes major patent filing office and sponsors. The data analysis provides a comprehensive description of lung cancer trials.

Diagnosis and management of small pulmonary atypical carcinoid tumor associated with Cushing syndrome

Ectopic adrenocorticotropic hormone ( ACTH) syndrome is rare and identification of its source is often challenging. We report the case of an ectopic Cushing syndrome in a young adult male secondary to an occult ACTH producing atypical carcinoid tumor. Extensive biochemical and imaging workup was unrevealing. The diagnosis was aided by Ga-DOTA PET scan demonstrating a suspicious left upper lobe lung nodule. The patient underwent video-assisted thoracoscopic exploration with wedge resection and mediastinal lymphadenectomy of a T2aN2M0 atypical carcinoid, resulting in the normalization of ACTH levels and complete resolution of symptoms. The role of a Ga-DOTA PET scan in diagnosing pulmonary carcinoid tumors and their management are discussed.