Tarceva and a infusion? - 1269486

Hi wadvocator,

It maybe avastin. There are studies on it that look promising if you fit the bill and avoid the likelihood of side effects. You don't need a study to get both at once though I'd imagine insurance would be a hurdle.

http://cancergrace.org/lung/2014/06/13/asco_2014_avastin_tarceva_help_e…
http://cancergrace.org/lung/2014/06/10/kato-erlotinib-with-or-without-b…

Janine

This fits with the subject of using tarceva in combination with another drug. http://cancergrace.org/lung/2015/04/25/pfs-debatable-endpoint-in-lc/

We should hear from a doctor in a few.

edit to add, this is such new and questionable (new territory) info that there's no normal, at least yet.

I agree w/ our lovely moderator that this is not standard. The data at this time consist of one prospective trial done in Japan in which patients were randomly assigned to receive erlotinib 1st line or erlotinib + bevacizumab (Avastin). The group getting both seemed to haave a longer duration of benefit from the treatment than the group getting erlotinib alone. I personally have not extended this observation to adding bev mid-stream for people already on erlotinib or even to considering this as an option at resistance, though I know some docs have done the latter. I think we just need to wait and see what further data show.

Dr. Sequist,

Thank you for the reply. I personally have been wondering why my oncologist is not in favor of this combination also.

What is your opinion on the ATLAS and BeTa Lung studies cited in Dr. West's article, which both show a benefit for asians and for never-smokers. Would your opinion be different for your asian or never-smoker patients? Particularly for your east asian patients, wouldn't a Japanese study with n=154, all east asians, be at least as strong as a US phase III with maybe 50 east asians?

The FDA cites a single study with 174 patients for the approval of tarceva as first line treatment in 2013. 8 years passed between the FDA approval of Tarceva in the second line and the approval of Tarceva in the first line. As an EGFR+ patient with brain metastases currently on first line Tarceva, I shutter to think what my treatment would have been just two years ago. In the era of precision medicine, what is the burden of evidence required to change practice?

I'm confused as to why most oncologists do not share the opinion of Dr. West on this combination. As one of the world's leading thoracic oncologists, I hope you can enlighten me.
( or even better, if you share this opinion ;)

Thanks,

The ATLAS and BETA studies were done in all lung cancer patients, and I think the benefit trends for Asians and non-smokers had to do with the fact that those w/ EGFR mutations did better. I do agree this is a promising combo. It's just that all the studies have been done in the upfront setting and we don't have any signal yet for adding it midstream or at the time of resistance. Furthermore, there is a history in the field of lung cancer of some studies done in Japan having opposite results in the US when tried to replicate here, so there is some degree of wanting to make sure before everyone jumps on the bandwagon. If I were going to recommend this to a patient of mine currently, it would be at the time of starting therapy, not midway through. And I would let them know that the risk of side effects (including fatal side effects) would be higher than w/ erlotinib alone.

also, just to note that although official FDA approval didn't come for erlotinib in the 1st line setting for EGFR mutants, it was standardly being used for that indication in some centers by 2005-6 and really everywhere by 2009.

I would just add to Dr. Sequist's last paragraph by pointing out that some of the delay in approval for Tarceva as first-line therapy for EGFR mutants was due to the early use of other forms of testing for EGFR rather then actual mutation testing, which led to the early conclusion that Tarceva did not provide a significantly greater benefit based on EGFR status. After it became clear that patients with activating EGFR mutations fared better with Tarceva than with standard chemo, it was approved as first-line treatment for such patients.

JimC
Forum moderator

Is it possible that differences in driver mutations among US and Japanese populations account for the historical differences in study outcomes? We already know that the EGFR mutation has much higher incidence in East Asian populations (~50%) compared to European populations (~10%) and that the presence of this mutation correlates to a strong response to EGFR inhibitors. Could this difference or other genetic differences in the tumor lead to differing responses in the two populations?

It is. Genetics play a huge role here and there's certainly plenty we don't understand. There are also differences in how trials are managed.