Tarceva, Iressa and EGFR screening.

No Duh.

Can't believe I missed this yesterday. In the NEJM there is an article talking about Tarceva therapy (Very Expensive) and that it targets lung cancers that have EGFR mutations. So if you don't have those mutations, why would we expect you to benefit from these expensive drugs first line?

Wha?

Ok let me explain.

Read this first

Iressa and Tarceva are EGFR tyrosine kinase inhibitors, which interfere with cancer cells' ability to multiply. People with certain mutations respond. In fact, I heard Mike Murray talk about the Lazarus response to Iressa which was published back in 2004

We tried a novel treatment and found that in certain tumor types, those with EGFR mutations, deletions in exon 19 and L858R primarily had better response to treatment with these TK EGFR inhibitors.

So, now we have what is a prospective trial assessing the utility of genotyping for therapy. This trial took 3 years to complete.

In addition, there was another study published which showed a head to head trial of toxic IV chemo versus targeted molecular therapy in a group highly likely to have EGFR mutations. Guess what they found? Yup, better outcomes with EGFR TK inhibitors and best outcomes in those with EGFR mutations......

They found:
Gefitinib is superior to carboplatin–paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.

The data are stunning. The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin–paclitaxel.

But the subgroup findings are where this personalized medicine approach had the most teeth with again, a very, very expensive drug.

In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin–paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001),> the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin–paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001).

This will be music to the comparative effectiveness gurus ears. Have an expensive drug? Test first to see if it works. Then give it........

Brilliant.

The Sherpa Says: We need more studies like this in many, many more fields. They will come, I am certain of that, which is why I am where I am.........