Targeted treatments for lung cancer likely to drive field forward

WASHINGTON — Recent progress in the use of genomics to treat lung cancer is likely to advance the field of cancer treatment, according to Mark G. Kris, MD, the Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center.

“It’s not one-size fits all anymore,” Kris said during his presentation at the U.S. News & World Report’s Hospital of Tomorrow Forum. “The difference is, we now have a better knowledge of biology, and an ability to test for these concepts that we’ve discovered; and we have these targeted therapies.”

Mark G. Kris

Kris discussed the beginnings of the groundbreaking work in lung cancer genomics, in 2003, with a patient at Memorial Sloan Kettering, who had an extraordinary response to the drug gefitinib (Iressa, AstraZeneca). This which led to research linking gefitinib sensitivity to EGFR mutations.

“This set the whole story in motion,” Kris said.

After the same discovery was made independently at two other institutions, researchers were inspired to look for other genetic drivers in tissue tumors. Kris said they found that in lung cancers, the majority had genetic drivers, which seemed to play an important part in cancer cells’ ability to grow and thrive. Attacking these drivers, therefore, could significantly impair cancer cells. This is known as “oncogene addiction,” he said, and it is considered cancer’s “Achilles’ heel.”

Kris said Memorial Sloan Kettering’s Marc Ladanyi, MD, developed multiplex assays for genetic mutations in lung cancer, and by 2004, the hospital had these tests available in-house.

Subsequently, Memorial Sloan Kettering and 13 other hospitals undertook a collaborative project to genotype 1,000 lung cancer cases.

“This was a change in the paradigm,” he said. “These were tissues of people with the illness, obtained at diagnosis. This was not a biobank. What we created as an information biobank; we shared information.”

The results were very consistent with previous findings: a genetic driver was detected in 64% of the tumors. The results from the genotyping were sent to the patients’ physicians, who ultimately used them to guide treatment. In 28% of the cases, the physicians were able to treat the patient with a targeted therapy.

“That’s fundamentally different from what’s done before,” Kris said.

Another study, published in the Journal of the American Medical Association in May of 2014, reported that in patients with genetic drivers, treatments targeted to those drivers yielded improved outcomes.

“The patients whose treatment was targeted to genetic drivers survived an average of one year longer than those who didn’t receive targeted treatment,” he said. “These numbers are far from desirable, but they do show an advance in this really tough field.”

Kris noted that while there will be regulatory hurdles involved in making these targeted treatments widely available for all cancers, he believes this is the future of addressing this complex disease.

“To me, the biggest understanding in cancer in the last 40 years is that it’s not cancer, it’s cancers,” he said. “We’ve totally underestimated cancer; we were so naive saying ‘we’re going to have a war on cancer’ – there’s no such thing as ‘cancer.’”

For more information:

Kris MG. JAMA. 2014;311(19):1998-2006. doi:10.1001/jama.2014.3741.