Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs
Begun in 2008, the first LCMC study was a multi-institutional program for investigating the frequency of selected oncogenic drivers in advanced lung cancers.
Using the results to treat participants with targeted therapies, either as part of standard clinical care or on investigational protocols, the study demonstrated the feasibility of widespread implementation of mutational profiling in the clinical care of lung cancer patients.
With 14 institutions participating and over 1,000 patients enrolled, the study was one of the largest of its kind to address the many challenges that arise in the course of molecular testing of solid tumors for therapeutic decision-making.
The Impact of Smoking and TP53 Mutations in Lung Adenocarcinoma Patients with Targetable Mutations
Building on the initial accrual of 1,000 patient samples from the first study, the second LCMC trial accrued an additional 1,000 patients. This cohort, with stage IV lung cancers whose tissue samples were tested with a larger panel of molecular targets, received approved medications or were again enrolled into “matched” therapeutic trials.
These two studies demonstrated that oncogenic drivers were detected in more than half of patients with lung adenocarcinomas and that treating these patient with targeted therapies improved survival. The LCMC2 trial also established that secondary genetic alterations that are not drivers (e.g. p53) could influence the outcomes of patients receiving targeted therapy.
Ultimately, these studies led to major changes in guidelines for biomarker testing including advocating for routine next generation sequencing at diagnosis.
A Study of Atezolizumab as Neoadjuvant and Adjuvant Therapy in Resectable NCLC
With success in patients with stage IV disease, the LCMC3 study shifted attention to early stage lung cancers. For the first time, the study scope included thoracic surgery leaders from member institutions, recognizing their central role in care and research in the peri-operative setting.
With enrollment begun in 2017 and completed in 2020, LCMC3 was designed as a neoadjuvant and adjuvant trial of immune checkpoint blockade for stage IB-IIIA non-small cell lung cancer.
The goals of this study included providing early stage patients with a new treatment option and leveraging the LCMC’s expertise in multicenter studies to address questions about the biology of response and resistance to immunotherapeutics.
Work is currently underway on LCMC4, which is focused on genomic testing but expands on our work in the neoadjuvant setting. For additional information on LCMC4, please click here.