The National Cancer Institute has launched a series of trials called ALCHEMIST, designed to identify early-stage lung cancer patients with tumors that harbor certain uncommon genetic changes and evaluate whether drug treatments targeted against those changes can extend survival.
“We believe that the findings from ALCHEMIST will not only help answer an important question about the addition of targeted therapies in earlier-stage disease but will also help us in understanding the prevalence and natural history of these genomic changes in earlier-stage lung cancer,” Shakun Malik, MD, Head of the NCI's Thoracic Cancer Therapeutics Division, said in a news release.
“We also hope to gain a better understanding regarding the genetic changes in the tumor at the time of recurrence. The findings will help to define clinical, biologic and molecular behaviors of this type of lung cancer.”
ALCHEMIST—which stands for Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials—is supported by the NCI with coordination of the component trials by the Alliance for Clinical Trials in Oncology and the ECOG-ACRIN Cancer Research Group. All of the NCI-supported National Clinical Trials Network (NCTN) groups collaborated in the development of ALCHEMIST and are participating in the component trials, the release noted.
Ramaswamy Govindan, MD, OT's Clinical Advisory Editor for Oncology, who is a member of the ALCHEMIST Project Core Committee and Professor and Co-Director of the Section of Medical Oncology at Washington University School of Medicine, explained that the ALCHEMIST trials provide a mechanism, for the first time, to expeditiously evaluate targeted therapies in molecularly defined subgroups of patients with following surgical resection and standard postoperative therapy in patents with non-small-cell lung cancer.
“Apart from studying molecularly targeted therapies in early-stage NSCLC, we will learn a lot about genomic alterations in lung adenocarcinoma through these trials,” he said.
Patients enrolled in the trials will need to undergo surgical removal of their tumors; have been diagnosed with lung adenocarcinoma or similar types of lung cancer as identified by examining the tissue; and complete standard therapy after surgery, consisting of chemotherapy with or without radiation therapy as prescribed by their physician.
In the ALCHEMIST screening trial, the surgically removed tissue will be tested in a central laboratory for certain genetic changes in ALK and EGFR genes. Participants with tumors found to harbor EGFR mutations or rearrangement of the ALK gene will then be referred to one of two randomized, placebo-controlled ALCHEMIST treatment trials. These studies will evaluate the value of adding therapy with specific agents targeted against two genetic alterations, erlotinib (EGFR) and crizotinib (ALK), in the postoperative setting.
Although both of these drugs are approved for the treatment of patients with advanced forms of lung cancer whose tumors have the targeted genetic alterations, it is not known if the agents will be beneficial when given to patients who are clinically free of disease. The goal of the trials is to determine whether erlotinib or crizotinib will prevent lung cancer recurrence, as well as prolong life, when used against tumors that carry specific mutations.
Monica Bertagnolli, MD, head of the Alliance, the lead network for ALCHEMIST, said, “This approach highlights the ability of NCTN to efficiently screen large numbers of patients in order to identify those with early-stage EGFR mutant or ALK-rearranged lung cancer. Without this capability, it would be impossible to identify a sufficient number of patients needed to perform clinical trials to determine whether EGFR or ALK inhibitors prolong survival in early-stage lung cancer.”
Information from the NCI notes that ALCHEMIST incorporates several other aspects of evolving clinical research and medical practice, including DNA sequencing and genomic analysis of tumor tissue, and possible additional genomic analysis at the time of lung cancer recurrence.
Moreover, every participant will also be studied for cancer risk characteristics, and their tumor tissue will be analyzed with advanced sequencing technologies in a research genomics initiative conducted by the NCI Center for Cancer Genomics, capitalizing on the foundation of The Cancer Genome Atlas.
The hope is that the results from ALCHEMIST can also benefit future lung cancer patients by helping scientists to:
- Screen for molecular features that may predict response to a drug with a given mechanism of action;
- Analyze tumor specimens at relapse to define mechanisms of resistance; and
- Develop a public database that links clinical outcomes with molecular tumor characteristics.
ALCHEMIST is the second precision medicine clinical trial to launch as part of the NCTN. The first, Lung-MAP, for patients with advanced squamous cell lung cancer, launched in June.