Tarceva, generic erlotinib, is a new treatment for non-small cell lung cancer that works by targeting the epidermal growth factor receptor (EGFR). It doesn’t work that great and can cost up to $50,000 a year. As such, its class of medications has been reserved for second or third line treatment.
Since lung cancer, however, typically presents at a late stage and has extremely short survival time, any medication that offers some chance of better health is highly appreciated.
About 80% of lung cancers are non-small cell, and greater than 60% of lung cancers are detected at Stage III or IV.
Some recent, major studies have led to Tarceva being viewed as more effective than gefitinib, a very similar drug with almost identical action.
Response and efficacy:
The major study that made Tarceva seem promising was in 731 patients with resistant cancer. Those treated with Tarceva had median survival of 6.7 months, while those given placebo had just 4.7 months.
Gefitinib, the related drug, showed very positive results in one study which had an objective response rate of 19% and median survival of 8 months. This is important because they are similar medications. Another major study, however, the ISEL, which looked at 1692 patients, showed no survival benefit of gefitinib over placebo, a major part of why it has fallen from popularity.
That said, both gefitinib and erlotinib may be more effective in certain types of people. They may, for instance, be more effective in people who never smoked, in Asians, and in women.
A Phase II study, for instance, gave gefitinib to 54 lung cancer patients who were Asian and had never smoked plus had adenocarcinoma. They had a significant increase to median survival of 7 months.
The TRIBUTE study gave Tarceva to non-smokers and showed an impressive 22.5 months survival versus 10 without.
Studies are currently analyzing whether Tarceva makes sense to be given as a first-line therapy.
In Tarceva, but interestingly not so much gefitinib, response to medication is often predicted by the presence of rashes. Worse rashes may mean better response. In one study, for instance, those who had the worst rashes had a median survival of 19.6 months, while those with milder rashes only had 8.5 months.
Mutations in EGFR
Some have hypothesized that response to this class of medication can be predicted from mutations in the epidermal growth factor receptor. This would help explain certain population response differences, as 10% of NSCLC has somatic mutations in Europeans and North Americans, as opposed to a much higher 30-40% mutation rate in East Asian.
Tarceva Side Effects:
28% have shortness of breath
18% have fatigue
9% have anorexia
9% develop rash
6% have diarrhea
More rarely are there eye reactions, skin blistering, and liver or kidney problems.
Epidermal growth factor (EGF) is a stimulatory messenger that makes cells replicate. Its receptor is a promising target because a very high percentage of cancers have some abnormality associated with it. Some overexpress EGF, while in others, the receptor itself is too sensitive.
While we’re able to target the EGF and its receptor, however, the clinical benefit is at best modest. This is probably due to the ability of the body to mutate resistance by various means, or because our current drugs aren’t strong enough. They only temporarily knock the receptor out, for instance, while new drugs may irreversibly do so.
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