Dan J. Raz, MD
While systemic therapies have steadily moved through the pipeline for patients with non–small cell lung cancer that is more advanced or metastatic, the same cannot be said for those with early-stage disease—even though approximately 50% of this patient population will relapse following surgery and standard chemotherapy. However, the ongoing Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials (ALCHEMIST) are looking to change this.
ALCHEMIST is a group of 3 randomized clinical trials seeking to determine whether adding adjuvant targeted therapy based on identified molecular abnormalities will improve outcomes and lower risk of recurrence. For example, the first phase, ALCHEMIST - Screening Trial (A151216), will test patients’ tumors for EGFR mutations and ALK translocations. If positive for EGFR, they will be referred to the ALCHEMIST - EGFR Treatment Trial [A081105] where they will be randomized to receive adjuvant erlotinib (Tarceva) or placebo. If positive for ALK, patients will be referred to the ALCHEMIST - ALK Treatment Trial (E4512) and will be randomized to receive crizotinib (Xalkori) or placebo as adjuvant treatment.
If a tumor does not test positive for either EGFR or ALK, they are then put on the ALCHEMIST – Immunotherapy Treatment Trial [ANVIL; EA5142] where they will receive adjuvant nivolumab (Opdivo) or observation.
“The ALCHEMIST trial is a really important trial and I hope that people refer patients to centers where they are doing the [study] because it’s important and the more patients that get put on the trial, the quicker it gets done,” said Dan J. Raz, MD. “While there are not a lot of biomarkers right now that are useful for early-stage lung cancer to assign whether patients get therapy, there is a lot of very interesting research.”
Raz, co-director, Lung Cancer and Thoracic Oncology Program, assistant professor, Division of Thoracic Surgery, Department of Surgery, and thoracic surgeon at City of Hope, shared his insight on the ongoing ALCHEMIST trial and some novel techniques, such as tissue slice culture, that are propelling the field of lung cancer forward in an interview during the 2017 OncLive®
State of the Science SummitTM
on Advanced Non–Small Cell Lung Cancer.
OncLive: You spoke on surgical resection in an era of biomarker-driven therapy in lung cancer. What has changed here?
: A lot has changed in lung cancer in general, in terms of personalized medicine and using a patient's own tumor to come up with more specific treatments. I spoke about how it relates to patients with earlier-stage disease who are having surgery. Currently, there is not a whole lot of personalized medicine we do for patients who are undergoing surgery, but there are a lot of advances we are making. There are new clinical trials and some research ideas that I spoke about to try to introduce the topic.
You mentioned the ALCHEMIST trial in your lecture. Can you discuss that a little bit and the potential impact of this trial’s findings?
That is a very important trial for patients with lung cancer, but especially for those who have earlier-stage disease. What this trial does is it looks at the mutational profile of patients with lung cancer who have undergone surgical resection and earlier stage disease—so stage Ib to IIIa. It allows them to receive standard therapy, but then based on their mutational profile, they get additional therapies if they have certain changes.
There are 3 separate trials within this trial. One is for patients with sensitizing EGFR mutations who get erlotinib or observation. The other one is for patients who have an EML4-ALK translocation who receive crizotinib or placebo. They get randomized. The third trial is for patients who don’t have any of these mutational changes; they are eligible to get immunotherapy for 1 year. Recruiting is probably going to be a while until all the results are ready.
What other trials in this space are showing interest?
There are a few different biomarkers that have tried to evaluate which patents are sensitive to standard chemotherapy. Unfortunately, most of those have not really panned out, but there are a few clinical trials that are still evaluating certain DNA-repair enzyme changes that might be promising. We'll have to see what the results of those are.
One thing I spoke about is using a patient's tissue—to culture the tissue and treat with different agents and see how those respond. That is something that has been around for a long time, but there have been advances, techniques, and a renewed interest because of personalized medicine in those types of techniques.