Gene Signature May Help Refine Lung Cancer Treatment
Article date: October 25, 2010
By Melissa Weber
Doctors are closer to being able to predict which early-stage lung cancer patients may benefit from chemotherapy after surgery—and which patients may be able to avoid it altogether, sparing themselves the unpleasant side effects of unnecessary treatment.
In a study recently published in the Journal of Clinical Oncology, researchers examined a specific set of 15 genes in non-small cell lung tumors. Patients found to be at high risk for recurrence based on the tumor's gene signature lived longer if they got the chemotherapy drugs cisplatin and vinorelbine after surgery. For patients at low risk for recurrence, the drugs offered no benefit, and might have been detrimental.
Researchers say the gene signature could give doctors a tool they’ve never had: a marker that identifies patients who have a good prognosis—and therefore can likely skip chemotherapy after surgery—and also points out those who don’t.
“Our signature is the only one so far that shows that patients who are identified as poor prognosis by the signature, they actually benefit from post-surgery chemotherapy,” says Ming-Sound Tsao, MD, lead investigator of the study.
Guiding treatment decisions
In the study, researchers used the gene signature to separate cancers at high risk for recurrence from cancers that posed a low recurrence risk. For patients predicted to be at high risk, chemotherapy reduced their risk of death significantly. For patients with a good prognosis, on the other hand, chemotherapy had no impact on survival.
“Chemotherapy is tough,” says Tsao, a pathologist at the Princess Margaret Hospital in Toronto. “The patients who have been identified by the signature [as having a] good prognosis can be spared from the toxicity.”
While the results are promising, they will need to be confirmed in future trials, the researchers noted.
Canada-based Med BioGene is currently developing the test under the brand name LungExpress Dx. The test is not yet commercially available in the US.
Gene signature tests to aid in treatment decisions are currently available for some other cancers, including the Oncotype DX Colon Cancer Assay for stage 2 colon cancer, and Oncotype DX Breast Cancer Assay, MammaPrint, and Breast Cancer Index for patients with early-stage breast cancer.
Knowing what works ahead of time
Treating all patients the same “makes no sense,” says lung cancer expert Roy Herbst, MD, PhD, of M.D. Anderson Cancer Center in Houston. Finding biological indicators—commonly referred to as biomarkers—that can tell doctors who to treat more, who to treat less, and with what therapy, will ultimately result in the best outcome for every patient.
“Lung cancer tends to spread so quickly, and unless we know how to treat it most effectively—even if you find it early—there are cells that could metastasize. We need something predictive to tell us what drug to use or what cocktail [of drugs] to use,” Herbst says.
The best predictive biomarker for lung cancer at this time is the epidermal growth factor receptor, or EGFR. Patients whose tumors have an EGFR mutation are most likely to benefit from erlotinib (Tarceva), a drug that inhibits the cancer-promoting mutation.
Although erlotinib is currently approved only for patients with advanced disease, Herbst says every lung tumor—early-stage tumors included—should be tested for an EGFR mutation.
“When the surgeon operates and the initial pathology is done, we’d like to know the EGFR mutation status then.” That information, Herbst says, could be helpful if the patient doesn’t respond to chemotherapy or radiation.
He also advocates testing every patient for a new biomarker called ALK—the target of a promising investigational drug called crizotinib. If a prognostic biomarker can tell doctors how likely a cancer is to spread, then predictive biomarkers like EGFR and ALK can help match a patient to the right drug.
“If there’s a high chance that [an early-stage lung cancer] is going to spread, you might want to give them one of these agents sooner, versus if the chance is low, you might want to wait. Those are questions that are going to need to be addressed,” Herbst says.
Reviewed by members of the ACS Medical Content Staff
Citation: “Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non—Small-cell Lung Cancer.” Published ahead of print on Sept. 7, 2010 in the Journal of Clinical Oncology. First author, Chang-Qi Zhu, Ontario Cancer Institute, University of Toronto.
ACS News Center stories are provided as a source of cancer-related news and are not intended to be used as press releases.
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