The National Cancer Institute (NCI) has launched an ambitious new nationwide clinical trial to find out if two molecularly targeted drugs that have improved outcomes in advanced lung cancer can increase survival of patients with early-stage lung cancer that has been surgically removed.
Dana-Farber Cancer Institute researchers Pasi Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology at Dana-Farber, and Geoffrey Oxnard, MD, are leading the screening phase of the trial, in which some 6,000 to 8,000 patients will have their tumors tested for uncommon genetic alterations that are associated with improved response to targeted cancer drugs. Those who have the alterations will randomly receive either a targeted drug or a placebo, and all patients will be followed for five years to determine if the drug treatment prolongs survival.
One of the genetic alterations, in the EGFR gene, is found in about 10 percent of patients with adenocarcinoma of the lung, and 5 percent have an alteration in the ALK gene.
The opening of the clinical trial, called ALCHEMIST, was announced Monday by the NCI and by two NCI organizations that coordinate clinical trials. One is the Alliance for Clinical Trials in Oncology, and the other is the ECGG-ACRIN Cancer Research Group. ALCHEMIST is an acronym for the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials.
Patients will be recruited at multiple centers across the country over the next five or six years. To be eligible, patients must already have had surgery to completely remove their lung tumors, and must have completed any adjuvant (follow-up) treatment such as chemotherapy and radiation. Samples of the removed tumor will be analyzed for the presence of EGFR and ALK mutations.
Patients found to have EGFR mutations in their tumors will be referred to a trial of the drug erlotinib (commercial name Tarceva®), while those with ALK mutations will enter a separate trial of treatment with crizotinib (Xalkori®). In each trial, patients will be randomized to the drug or a placebo. Trial leaders expect about 800 patients to receive a drug or placebo in the two treatment trials. All patients will be followed for five years, including the large number of patients who will be found to lack either mutation.
Although the Food and Drug Administration has approved erlotinib and crizotinib for treatment of advanced lung cancer, it’s not known whether the drugs will be effective in patients who have undergone complete removal of lung tumors with one of the mutations.
More than half of patients experience recurrences of lung cancer, even if it was completely removed, because tiny clumps of cancer cells invisible to the surgeon metastasize through the blood vessels to cause new cancers.
"We are excited to participate in this ambitious undertaking," said Oxnard. "Through this large-scale collaborative effort to genotype thousands of early-stage lung cancer patients, ALCHEMIST allows us to test better adjuvant treatments while simultaneously teaching us important lessons about the genetic complexity of lung cancer."
The trial will investigate, in addition to the potential survival benefit of the targeted drugs, each patient’s lung cancer risk characteristics, and will analyze tumor specimens when patients relapse to determine how their tumors become resistant to treatment.
Partial funding for the trial was provided by the Robert T. and Judith B. Hale Fund for Pancreatic Cancer Research.