The management of some patients with lung cancer has been revolutionized over the past 24 months by the discovery that approximately 15% to 20% of lung adenocarcinoma tumors harbor epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) translocations, and these gene mutations can be selectively targeted with oral medications.
Oncologists report that they are seeing a dramatic improvement in survival for patients who have tumors with these specific mutations. Now, a new approach based on this discovery is underway to try to cure early-stage lung cancer in patients who harbor these genetic alterations.
In August 2014, the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST) were launched and they will screen approximately 8,000 patients with lung cancer. Patients will undergo surgical removal of their tumors.
After completing standard therapy after surgery, the patients who harbor EGFR mutations or rearrangement of the ALK gene will then be referred to two randomized, placebo-controlled ALCHEMIST treatment trials. Patients will then be treated with targeted therapy (erlotinib for EGFR and crizotinib for ALK). Both of these agents are approved for treating patients with advanced-stage lung cancer.
“We are moving the targeted therapies into early-stage disease,” said Ramaswamy Govindan, MD, who is the principal investigator of the EGFR treatment component of ALCHEMIST.
“In the early stage, we hope to cure these patients and this trial will see if we cure more patients. The hope is to improve rates in patients with early-stage lung cancers who have these types of mutations,” he explained. “This is an important study because it is the first national study that is seeing if we can cure patients who have early-stage lung cancer.”
Dr. Govindan, a professor in the division of medical oncology at Washington University School of Medicine in St. Louis, Missouri, said that this trial marks a new era in lung cancer research because it incorporates DNA sequencing and genomic analysis of each patient’s tumor. The researchers plan to also conduct additional genomic analysis at the time of lung cancer recurrence.
Each study participant will be analyzed with advanced sequencing technologies in a research genomics initiative conducted by the National Cancer Institute Center for Cancer Genomics. Approximately 800 patients will be enrolled in the treatment arms of this integrated precision medicine trial.
“These drugs have not been studied enough in early-stage disease. It is possible that they may be even more effective in early-stage disease. In advanced disease, you are controlling the symptoms and extending lives. With early-stage [disease], we are hoping to cure the patients,” Dr. Govindan told Cancer Therapy Advisor.
As part of this study, all screened participants, regardless of their tumors status, will be followed for 5 years. It is hoped that ALCHEMIST will help lead to a much greater understanding of the prevalence and natural history of genomic changes in earlier-stage lung cancer.