Lung cancer patients with pockets of resistance prolong disease control by 'weeding the garden'

The central skill of cancer is its ability to mutate – that's how it became cancerous in the first place. Once it's started down that path, it's not so difficult for a cancer cell to 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 new, targeted cancer therapy drugs.

Two of these targeted drugs are crizotinib and – they do wonders for the 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, inevitably, inexorably stop working.

A University of Colorado Cancer Center study published in the December issue of the International Association for the Study of 's (IASLC) shows that when pockets of resistant cancer develop, it's often possible to zap these resistant pockets with focused, targeted radiation while continuing crizotinib or erlotinib to maintain control of the majority of the disease that continues to depend on the primary mutation.

"We liken this to weeding the garden," says Andrew Weickhardt, MD, senior clinical fellow at the CU 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 in one case, surgery), and continue the same drug, which was obviously working elsewhere."

This study of 65 patients showed that continuing either crizotinib or erlotinib after the treatment of resistant pockets was associated with more than half a year of additional .

The benefit was especially robust when the metastatic lung cancer progressed in the brain. The brain is unfortunately a common site of progression because the molecules of crizotinib and erlotinib have difficulty in passing from the bloodstream into the brain, across the so-called blood-brain barrier. sit in the brain as in a robber's cave, hidden away from the drugs.

"We expect using radiation to zap these pockets of cancer in the brain, and then continuing the targeted therapy to become the standard of care," says CU Cancer Center investigator, Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at University of Colorado Hospital.

There was also a smaller but still significant progression-free survival benefit for using this approach in patients whose cancers progressed first outside the brain.

If and when pockets of crizotinib- or erlotinib-resistant lung cancer are detected, "Clinicians should consider using radiation in the body and especially in the brain to weed the garden while continuing the drug, when there is good ongoing control of the cancer in other sites in the body," Weickhardt says.

add to favorites email to friend print save as pdf

Related Stories

Study examines drug resistance in ALK positive lung cancer

Jan 19, 2012

Scientists from the University of Colorado Cancer Center have once again advanced the treatment of a specific kind of lung cancer. The team has documented how anaplastic lymphoma kinase (ALK) positive advanced non-small cell ...

Benefit of targeted lung cancer therapy confirmed

Jun 03, 2011

A drug that targets a specific type of lung cancer shows a dramatic response in more than half of the people who take it. The drug, called crizotinib, has been in clinical trials since 2006, and the results from the largest ...

Recommended for you

Immune checkpoint inhibitors may work in brain cancers

Nov 21, 2014

New evidence that immune checkpoint inhibitors may work in glioblastoma and brain metastases was presented today by Dr Anna Sophie Berghoff at the ESMO Symposium on Immuno-Oncology 2014 in Geneva, Switzerland.

New model of follow up for breast cancer patients

Nov 21, 2014

Public health researchers from the University of Adelaide have evaluated international breast cancer guidelines, finding that there is potential to improve surveillance of breast cancer survivors from both a patient and health ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.