"While it is premature to make any conclusions about survival, we found that this treatment induced regressions that were often dramatic in patients with advanced BAC, and that the responses seem more durable and meaningful than what we have seen with chemotherapy," said the study's lead investigator Vincent Miller, MD, medical oncologist at MSKCC. "The treatment was especially effective in those patients who never smoked," he added.
Erlotinib is a small molecule that works by blocking the activity of an enzyme called "epidermal growth factor receptor (EGFR) tyrosine kinase," which helps communicate information within the cancer cell. EGFR is found on the surface of many tumor cells and may be involved in the growth and virulence of those cells.
BAC has certain pathologic and clinical features that distinguish it from other lung cancers. Approximately 3 percent of all lung cancer patients have what are called pure BAC tumors, but overall about 20 percent of an estimated 35,000 non-small cell lung cancers diagnosed each year possess some BAC features. BAC tends not to metastasize, but rather to spread within the lung causing symptoms such as shortness of breath and sputum production. Chemotherapy usually does not work as well for people with this type of lung cancer as it may in other types. BAC is increasing in incidence and it is more common in women and in individuals who never smoked.
In this phase 2 study, 33 patients with BAC or adenocarcinomas with BAC features were accrued to the trial and began treatment between June and December of 2002. Nine of the patients never smoked. Eight out of 30 patients who completed at least one month of therapy achieved a partial response. Of the eight patients who responded, five never smoked, two smoked one pack a day for less than 10 years, and one was a heavy former smoker. Two patients died from progression of their disease.
"The particularly encouraging activity of this drug in never-smokers suggests that tobacco-related genetic changes in this patient population may influence resistance to this drug. Further research is necessary to address this possibility," said Dr. Miller.
According to the study's authors, BAC has not been well studied, yet it is a significant problem that needs to be looked at separately and perhaps treated differently in the future.
Previous studies of erlotinib have shown promising activity in the treatment of advanced non-small cell lung cancer patients whose tumors had not responded to initial chemotherapy, and anecdotally, some of the most striking results occurred in individuals with BAC. This led investigators to conduct the current trial in an attempt to begin to better define the activity of this agent specifically in patients with BAC.
Patients in this study experienced modest side effects including rash and diarrhea, most of which seem to attenuate over time.
"This is not a panacea, but to see a therapy actually cause tumor regression in a meaningful percentage of patients with this disease is really unexpected and a pleasant surprise. The hope is to ultimately manage BAC like a chronic disease."
Investigators from Vanderbilt University Medical Center also contributed to the research, which was funded by Genentech Inc., South San Francisco, CA.
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