Metastatic Squamous Lung Cancer Research Articles

Afatinib for the Treatment of NSCLC with Uncommon EGFR Mutations: A Narrative Review.

Afatinib, the world's first irreversible ErbB family (containing four different cancer cell epidermal growth factor receptors, including EGFR, HER2, ErbB3, and ErbB4) inhibitor, is a second-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It can be used as a first-line treatment for locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR-sensitive mutation or for patients with locally advanced or metastatic squamous lung cancer whose disease progresses during or after platinum-containing chemotherapy. Currently, with the use of third-generation EGFR-TKIs, afatinib is no longer clinically indicated as the first choice for patients with NSCLC who have EGFR-sensitive mutations. However, afatinib showed a considerable inhibitory effect in NSCLC patients with uncommon EGFR mutations (G719X, S768I, and L861Q) according to a combined post hoc analysis of the LUX-Lung2/3/6 trials. With the development of genetic testing technology, the detection rate of uncommon EGFR mutations is increasing. The aim of this paper is to describe in detail the sensitivity of rare EGFR mutations to afatinib and to provide information and a reference for those suffering from advanced NSCLC who have uncommon EGFR mutations.

Second-line therapy and MicroRNA plasma level in metastatic lung cancer patients: case-control study

The first cause of cancer death was lung cancer among men and women. MicroRNAs are small noncoding regulatory RNAs with a length of 18–24 nucleotides. MicroRNAs could target more than 100 mRNAs, and they can affect many cellular processes. The objective of this study is investigating the role of miR-663a and miR-663b, in metastatic lung cancer patients compare with healthy people. The relationship between these microRNAs and chemoresistance was investigated through Real time polymerase chain reaction methodology used to determine the levels expression of miR-663a and miR-663b in the serum of 30 patients with metastatic lung cancer were treated with second line therapy versus 25 healthy individuals who follow up for one year. The resulted data showed that miR-663a expression was related to type of lung cancer and was significantly higher in metastatic squamous lung cancer group (P=0.012). While the expression of miR-663b was significantly correlated with the response to treatment, in which the expression of miR-663b was higher in the poor-response group (P=0.016). Inconclusion, this study showed that the high plasma level of miR-663a miR-663b may be related to chemoresistance in patients with metastatic lung cancer.

Rare Grade 3 Dermatologic Immune-Related Adverse Event: Psoriasis in Patient with Metastatic Lung Cancer, A Case Report

We report a case of a 62-year-old men with a diagnosis of metastatic squamous lung cancer receiving the anti-PD1 pembrolizumab therapy. After the second maintenance treatment cycle, the patient reported a rare dermatologic immune-related adverse event, characterized by itchy psoriatic manifestations widespread >30% of the body surface. The diagnosis was confirmed by skin biopsy. Patient was treated according to guidelines without significant clinical response.

MA14.10 Clinical Outcomes in Metastatic Squamous Lung Cancer with Targetable Driver Alterations

Genomic profiling is not routinely performed for metastatic squamous (SCC) and adenosquamous (ASC) NSCLC. However molecular profiling may be ordered if demographic features suggest a higher likelihood of a targetable driver alteration (e.g. never or remote smoking history). Response and survival data are scant in pts with actionable alterations treated with targeted therapy. We reviewed the clinical data and molecular profiling (FISH, PCR, tissue NGS, ctDNA) of metastatic SCC and ASC pts treated at our institution from Feb 2010-Dec 2018. Pts with typical sensitizing mutations in EGFR or BRAF V600E or fusions in ALK or ROS1 treated with matched targeted therapy for ≥2 months were included in this analysis. Response assessment was based on RECIST v1.1. Among 261 metastatic SCC or ASC pts with available molecular profiling, 16 total pts (6%) were found to have actionable targets, consisting of 13 SCC and 2 ASC (median age 53, 81% female, 88% never-smoker). The distribution of driver alterations in this cohort was 56% (9/16) EGFR ex19del/L858R/G719A, 38% (6/16) ALK fusion, and 6% (1/16) BRAF. The overall objective response rate (ORR) and median progression free survival (PFS) to targeted therapy was 69% and 5.2 months respectively. By mutational subgroup, ORR was 67% (6/9) for EGFR, 67% (4/6) for ALK, and 100% (1/1) for BRAF. Median PFS was only 4.5 months (95% CI 3.0 – 6.0) for EGFR pts and 2.8 months (95% CI 0 – 6.4) for ALK pts, and the lone BRAF pt had a PFS of 8.5 months. In EGFR pts with available NGS, co-mutations in TP53 (75% [6/8]) and PIK3CA (38% [3/8]) were seen at rates higher than previously reported in EGFR+ ADC (TP53 55%, PIK3CA 12%; Blakely et al, Nat Gen 2017). In ALK pts with available NGS, co-mutations in TP53 (80% [4/5]) were also higher than recently reported in ALK+ ADC (24%; Kron et al, Ann Oncol 2018). Despite initial responses comparable to those previously reported in ADC, matched targeted therapy in pts with SCC and ASC histology is associated with shorter PFS. A higher prevalence of adverse co-mutations such as TP53 and PIK3CA may contribute to early targeted therapy resistance in these histologies. These findings may have implications for the use of targeted therapy in squamous lung cancer.

P2.03a-002 Patterns of Chemotherapy Use and Overall Survival (OS) of Patients with Stage IV Squamous Lung Cancer (SCC)

Chemotherapy is standard of care for patients with metastatic SCC. There is limited information on the use and outcome of patients with metastatic SCC who receive chemotherapy. We used the National Cancer Data Base (NCDB) to investigate the use and survival of patients receiving chemotherapy for stage IV SCC. The NCDB was queried for patients≥ 18 years, diagnosed with stage IV SCC between 2004-2013 for whom chemotherapy data was available. The percentage of patients receiving chemotherapy within 2 months of diagnosis was calculated. Patients were stratified by age (<50, 50-70 and >70 years), Charlson-Deyo comorbidity score (0, 1 and 2), gender, and period of diagnosis (2004-2006, 2007-2009, 2010-2012) to evaluate patterns of chemotherapy use. Median, 1-year and 2-year OS were calculated for patients that received chemotherapy using Kaplan Meier method. Among the 86,200 patients that met the eligibility criteria, 40,147 (46.6%) patients received chemotherapy, which included single agent (n=3,912; 9.7%) multiagent (n=32,737; 81.5%) and number of agents unknown (n=3,498; 8.7%). A total of 46,053 (53.43%) patients did not receive chemotherapy due to chemotherapy not recommended (n=5,397; 11.7%), patient refusal (n=6,119; 13.3%) and other/unknown reasons (n=34,537; 75%). Patients receiving multi-agent chemotherapy were younger than those receiving single agent chemotherapy (65.6 vs 71.5 years). Chemotherapy use declined with increase in comorbidity score (50.4% for score of 0, 44% for score of 1 and 36.2% for score of 2). The median, 1-year and 2-year OS for patients receiving chemotherapy were 7.5 months, 30.6% and 11.8% respectively (Table).Tabled 1OS for patients receiving chemotherapy by risk factorRisk factorMedian survival (months)1 year OS2 year OSAge<507.629.7%11.5%50-707.832.0%12.4%>707.028.5%10.8%GenderMale7.329.0%10.7%Female7.933.7%13.8%Year of diagnosis2004-20062007-20097.37.528.8%31.0%10.7%11.8%2010-20137.731.6%12.7%Charlson-Deyo comorbidity score0128.07.16.332.6%28.4%24.9%12.7%10.6%9.2%All patients7.530.6%11.8% Open table in a new tab Most patients with metastatic SCC do not receive chemotherapy. The OS for patients with metastatic SCC remains poor, especially in patients over the age of 70, in men and those with multiple comorbidities.

Nivolumab for refractory metastatic squamous non-small-cell lung cancer: fulfilling an unmet need.

Lung cancer is the leading cause of cancer death in the United States and worldwide (1,2). Approximately 85% of cases involve non-small-cell lung cancer (NSCLC), of which 30% will be squamous cell histology. Of those squamous cell lung cancers diagnosed yearly, it is estimated that more than 50% are metastatic at diagnosis. Until recently, the recommended treatment for good performance status patients with metastatic squamous lung cancer consisted of first-line platinum doublet chemotherapy followed, upon disease progression, by second-line single agent chemotherapy (1). Median overall survival from initial diagnosis of metastatic squamous lung cancer in patients who receive first-line platinum doublet chemotherapy ranges from 8-11 months (3,4). Therefore, effective new therapies are desperately needed. Building upon durable objective responses to the anti-programmed death-1 (anti-PD-1) antibody, nivolumab, reported in phase I studies, Rizvi et al. have recently published the results of a singlearm phase II trial of single-agent nivolumab in pretreated metastatic squamous lung cancer (5). In conjunction with headline results from a randomized phase III trial in secondline metastatic squamous lung cancer confirming improved OS for nivolumab compared with docetaxel, these data have led to the FDA approval of nivolumab for the treatment of metastatic squamous lung cancer after prior platinum-based chemotherapy (6).