Genomics Aids Lung Tumor Classification and Treatment

A study of thousands of lung cancer patients published in Science Translational Medicine adds to the groundswell of supportive evidence for the use of genomics in lung cancer classification and treatment. “Our paper provides a blueprint for how genomics can improve diagnostics, and, in turn, how better diagnostics can improve therapeutic decision making,” says lead author Roman Thomas, MD, a professor of genomics at the University of Cologne in Germany.

The paper describes two research efforts. In the first, scientists with the Clinical Lung Cancer Genome Project (CLCGP), an international consortium based in Cologne, compared the accuracy of genetic sequencing versus immunohistochemistry in tumor classification. After characterizing 1,255 tumors, the researchers concluded that the genetic methods allow more accurate assigning of tumors to therapeutically relevant groups, particularly for large cell carcinoma.

Large cell carcinoma tumors have historically been clustered together with adenocarcinoma and squamous cell carcinoma under the broader heading of non–small cell lung cancer (NSCLC). However, the CLCGP's results altered this traditional grouping. After being genomically analyzed, most large cell carcinomas were reassigned to one of the other two NSCLC subtypes.

“The data suggest that large cell is not a biologically valid entity,” says coauthor William Pao, MD, PhD, a professor of medicine and cancer biology at the Vanderbilt-Ingram Cancer Center in Nashville, TN. “It's more likely a poorly differentiated version of either adenocarcinoma or squamous cell carcinoma.”

The change in classification also has clinical implications, Thomas adds. Up to 15% of squamous cell carcinomas have fibroblast growth factor receptor 1 (FGFR1) amplifications, which serve as a target for FGFR1 inhibitors. This might open up some opportunities for treatment among patients who might previously have been diagnosed with large cell carcinoma and who have those amplifications.

In the second research effort, which prospectively evaluated the project's combined genomic and immunohistochemical diagnostic approach, the Cologne-based Network Genomic Medicine screened 5,145 lung cancer patients for a panel of roughly 20 lung cancer mutations.

The researchers were able to perform the combined genomic and immunohistochemical analysis on 3,863 of those patients, and many of them were eligible for approved targeted therapies or for treatment with experimental therapies in clinical trials.

The benefits of this approach were especially evident in patients with EGFR-mutant or ALK-rearranged lung cancers, says Thomas. Patients with EGFR mutations who were treated with an approved targeted therapy had a median overall survival of 31.5 months, compared with 9.6 months among those who had the mutations but did not receive the same drugs. Likewise, patients with ALK-rearranged cancer treated with crizotinib (Xalkori; Pfizer) had a median survival of 23 months, versus 11 months for those who didn't receive targeted treatment.

“This is one of the first papers to link comprehensive genomic and immunohistochemical analysis with clinical treatment on a large scale,” Pao says. “Results clearly show that genomic tumor analysis is beneficial to patient care.”