Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer: The ALCHEMIST trials

Ryan S. Alden, Sumithra J Mandrekar, Geoffrey R. Oxnard

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number37
JournalChinese Clinical Oncology
Volume4
Issue number3
DOIs
StatePublished - 2015

Fingerprint

Lung Neoplasms
Non-Small Cell Lung Carcinoma
Genotype
Placebos
Epidermal Growth Factor Receptor
Therapeutics
Recurrence
National Cancer Institute (U.S.)
Disease-Free Survival
Randomized Controlled Trials
Clinical Trials
Mutation
Neoplasms

Keywords

  • Adjuvant therapy
  • Clinical trial design
  • Non-small cell lung cancer (NSCLC)
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology

Cite this

Designing a definitive trial for adjuvant targeted therapy in genotype defined lung cancer : The ALCHEMIST trials. / Alden, Ryan S.; Mandrekar, Sumithra J; Oxnard, Geoffrey R.

In: Chinese Clinical Oncology, Vol. 4, No. 3, 37, 2015.

Research output: Contribution to journalArticle

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