Targeted treatment of resistant cancer may improve progression-free survival with some drugs

Pockets of resistant cancer can be treated with focused, targeted radiation while continuing therapy with the targeted drugs crizotinib or erlotinib, which maintains control of the majority of the disease that continues to depend on the primary mutation.

The central skill of cancer is its ability to mutate. Once mutation starts, a cancer cell can mutate again and again. This means that different tumors within a single patient or even different areas within the same cancerous deposit may develop different genetic characteristics. This heterogeneity helps cancer escape control by targeted cancer therapy drugs.

Two of these targeted drugs are crizotinib and erlotinib, which work well in patients whose cancers depend on the basic mutations that these drugs exploit. That is, until pockets of the cancer mutate again, pivoting their dependence away from the original, targeted mutation. Due to continuing mutation, the unfortunate reality is that while crizotinib and erlotinib extend patients' lives, the drugs eventually stop working.

This study involving 65 patients found that continuing crizotinib or erlotinib after treating resistant pockets was associated with an additional 6 months of cancer control. The benefit was particularly robust for metastatic lung cancer that had progressed in the brain. Because crizotinib and erlotinib have difficulty passing from the bloodstream into the brain, the brain is a common site of progression, where cancer cells can evade the drugs.

A smaller but still significant benefit in progression-free survival occurred with this approach in patients whose cancers first progressed outside the brain.

“We liken this to weeding the garden,” said Andrew Weickhardt, MD, senior clinical fellow at the Colorado University Cancer Center. “In nearly half of patients, when these drugs stop working, they stop working only in a limited number of sites. Given how well these people tolerate the medication, it made sense to us to treat these isolated spots with radiation (or, as in one case, surgery), and continue the same drug, which was obviously working elsewhere.”

This study was published in the Journal of Thoracic Oncology (2012; doi:10.1097/JTO.0b013e3182745948).

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