EGFR+ Lung Cancer

Next generation therapies proven to be highly effective, are in development for patients who have oncogene-driven non-small cell lung cancer (NSCLC), specifically those with alterations in EGFR, ALK, ROS1, and NTRK.

Roy Decker, MD, PhD, associate professor of therapeutic radiology, assistant professor of surgery (Otolaryngology), Clinical Research Program Leader, Therapeutic Radiology, Yale University, discusses stereotactic body radiation therapy (SBRT) in surgery for patients with early non-small cell lung cancer (NSCLC).

In addition to late patient presentation, the high mortality rate in lung cancer can be largely attributed to the complex nature of the disease and a very high rate of heterogeneity in the causative molecular abnormalities.

Immunotherapies (immune checkpoint inhibitors) and targeted therapies (tyrosine kinase inhibitors [TKIs] that target specific mutations in one or more oncogenic drivers) represent two of the most researched types of therapy under investigation for the treatment of non-small cell lung cancer (NSCLC).

An impressive array of newly approved treatments, as well as investigational agents, for non–small cell lung cancer (NSCLC) emerged in the first 6 months of 2015.

Martin Reck, MD, PhD, Head of Thoracic Oncology, Hospital Grosshansdorf, discusses the phase III SQUIRE trial in patients with non-small cell lung cancer (NSCLC) treated with necitumumab.

The University of Texas MD Anderson Cancer Center in Houston has been selected as the site for one of two new Genome Characterization Centers (GCCs) funded by the National Cancer Institute (NCI) and National Institute of Health (HHSN261200800001E).

Breakthrough therapy designation has been granted by the US Food and Drug Adminstration (FDA) to the combination of the BRAF inhibitor dabrafenib (Tafinlar) and the MEK inhibitor trametinib (Mekinist) as treatment for patients with BRAF V600E-mutant non–small cell lung cancer

Results from the phase III METEOR study showed that treatment with cabozantinib (Cometriq) improved progression-free survival (PFS) and overall survival (OS) compared with everolimus (Afinitor) in previously treated patients with metastatic renal cell carcinoma (mRCC).

Gefitinib (Iressa) was recently approved by the FDA for the frontline treatment of patients who have metastatic, EGFR-positive non-small cell lung cancer (NSCLC) with an exon 19 deletion or exon 21 (L858R) substitution.

Clovis Oncology has initiated the rolling submission process for rociletinib in EGFR T790M-positive advanced non–small cell lung cancer following prior treatment with a TKI.

Jennifer S. Temel, clinical director, Thoracic Oncology, Massachusetts General Hospital, discusses a phase III study that examined the impact of anamorelin in patients with advanced non-small cell lung cancer (NSCLC) and cachexia.

An assay that measures circulating tumor (ct) DNA in the urine can detect the early acquisition of epidermal growth factor receptor (EGFR) resistance mutations in patients with metastatic lung adenocarcinoma.

Researchers at the Wistar Institute Cancer Center have discovered a new potential circulating biomarker for non–small cell lung cancer. It is a cancer testis antigen expressed by a cancer/testis gene called AKAP4. The exciting prospect this heralds is the development of an accurate, quick blood test for early-stage NSCLC.

The next-generation ALK inhibitor alectinib has demonstrated robust objective response rates (ORR) in patients with ALK-positive non–small cell lung cancer, including those with central nervous system metastases.

An immunotherapy combination demonstrated an overall response rate of 27% in previously treated non–small cell lung cancer across a range of doses, according to results of an ongoing phase Ib study.

The FDA has granted a priority review to pembrolizumab as a potential treatment for patients with advanced non-small cell lung cancer following treatment with chemotherapy or a targeted therapy, if applicable.

Nivolumab (Opdivo) improved overall survival and was less toxic compared with docetaxel in chemotherapy-pretreated patients with nonsquamous non–small cell lung cancer.

MPDL3280A reduced the risk of death by 53% compared with docetaxel in previously treated patients with PD-L1-positive squamous and non-squamous non-small cell lung cancer.

D. Ross Camidge, MD, director, Thoracic Oncology Clinical Program, program director, Thoracic Oncology Clinical and Translational Research Fellowship, University of Colorado Denver, discusses MET as a secondary driver in lung cancer.

Edward S. Kim, MD, chairman, Solid Tumor Oncology and Investigational Therapeutics, Levine Cancer Institute, Carolinas HealthCare System, discusses combining bevacizumab with EGFR tyrosine kinase inhibitors (TKI) in the treatment of lung cancer.

John Heymach, MD, PhD, chair of Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, discusses the characteristics of three more KRAS subsets in lung cancer, which researchers discovered in a recent study.

Leaders of Roswell Park Cancer Institute (RPCI) in Buffalo, New York, have agreed to collaborate with the Center for Molecular Immunology (CIM) in Cuba to evaluate a therapeutic anticancer vaccine for non–small cell lung cancer (NSCLC) in the United States.

The third-generation EGFR inhibitor rociletinib demonstrated promising responses in patients with EGFR-mutated non-small cell lung cancer with or without the acquired resistance mutation T790M.

Despite their promise, checkpoint inhibitors are not effective in every patient, and research suggests the STING (stimulator of interferon genes) pathway may hold important clues as to why some tumors fail to respond.

A prospective study of retrospectively analyzed blood samples of patients with nonresectable pancreatic cancer found that plasma KRAS mutational burden correlates with overall survival (OS).

Pembrolizumab (Keytruda) achieved an overall response rate (ORR) of 45.2% among a cohort of patients with high PD-L1-expressing non–small cell lung cancer (NSCLC) in the phase I KEYNOTE-001 trial.

The availability of mutation-specific treatments and an increasing understanding of potential resistance mechanisms have provided immense opportunities for research and development of new therapies in lung cancer.

Abnormal driver mutations contribute to tumor progression and have been prime targets for many therapeutic studies in oncology; however, researchers are focusing more and more on the less-studied passenger mutations and their role in tumor progression.

Despite the availability of several new agents in the past 5 years for the treatment of melanoma, patients with advanced melanoma still suffer poor prognoses.