Genotype-directed targeted
therapies have revolutionized the treatment of metastatic
non-small cell lung cancer (NSCLC) but they have not yet been comprehensively studied in the adjuvant setting. Previous trials of adjuvant targeted
therapy in unselected early stage NSCLC patients showed no benefit versus placebo, however retrospective data suggests improved disease free survival (DFS) with
epidermal growth factor receptor (EGFR) inhibitors in patients with appropriate molecular alterations. A definitive prospective, randomized, placebo-controlled trial of targeted
therapies for NSCLC is needed to determine the efficacy of targeted
therapy following surgical resection and standard adjuvant
therapy. The principal challenges facing such a trial are (I) identification of actionable alterations in early stage patients; and (II) realization of sufficient enrollment to power definitive analyses. The ALCHEMIST trial (Adjuvant
Lung Cancer Enrichment Marker Identification and Sequencing Trial) was designed to overcome these challenges. Using the national clinical trials network (NCTN) of the National Cancer Institute (NCI), several thousand patients with operable NSCLC will undergo
tumor genotyping for EGFR mutations or rearrangement of
anaplastic lymphoma kinase (ALK). Following resection and completion of standard adjuvant
therapy, patients with EGFR-mutant NSCLC will be randomized to
erlotinib versus placebo (1:1), those with ALK-rearranged NSCLC will be randomized to
crizotinib versus placebo (1:1), while those not enrolled onto the adjuvant trials will continue to be followed on the screening trial. ALCHEMIST also provides for the collection of tissue at baseline and at recurrence (if available) to characterize mechanisms of recurrence and of resistance to targeted
therapy. Thus, ALCHEMIST is a platform for validation of targeted
therapy as part of curative care in NSCLC and creates an opportunity to advance our understanding of disease biology.