Can interstitial metastatic disease be cause by Erlotinib? - 1257022

mmac
Posts:2

I am stage 4 adenocarcinoma, 5 years post lobectomy 4 years on 75mgs Tarceva. (Two prior rounds of platinum and taxol chemo). I learned this week that I now have interval development of diffuse interstitial metastatic disease both lungs in addition to a meaningful progression on several nodules, < 2cm. There are are about 10-15 nodules in this size range.

My question is might this be actually caused by the Tarceva? - there is a research paper that suggests that there could be a linkage - and if so would a switch to another drug be indicated? At this time my physician supports the addition of Alimta and staying with Tarceva, no cause to change this treatment at the moment. I would be interested in your thoughts about Tarceva causing interstitial disease and the possible treatment next steps.

Thank you, M.Mac.

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JimC
Posts: 2753

Hi M.Mac,

I'm not familiar with the research paper to which you refer, but in general it isn't thought that a targeted therapy such as erlotinib "causes" a particular type of progression, but rather that resistant cancer cells tend to appear first in certain areas. With EGFR positive NSCLC and erlotinib, for example, often the first place the cancer progresses is in the central nervous system, perhaps because the drug doesn't reach that area in sufficient concentrations.

As far as whether to continue erlotinib and add another agent such as alimta, or simply discontinue erlotinib and switch to either another regimen or a trial of a new targeted therapy which seeks to overcome the resistance which has developed, you won't find consensus among the best lung cancer practitioners.

You can watch a podcast on the subject here: http://cancergrace.org/lung/2013/05/20/bonomi-manage-acquired-resistanc… On that page, under “Related posts” you will find other experts’ opinions on the same question, and you can see how even the top names in the field do not agree.

When she progressed on erlotinib, my wife's oncologist added alimta and she did achieve stability.

JimC
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Dr West
Posts: 4735

Jim highlighted the key points here. Indeed, adding standard chemo to Tarceva in people who have done well on Tarceva for a long time beforehand is a common approach, and one I often recommend for my own patients in this setting. That said, even the experts respectfully disagree on whether to continue an EGFR inhibitor when there is enough progression to require a change in systemic therapy.

I would be very surprised if someone who has tolerated Tarceva for a long time suddenly develops lung lesions, and the pattern you describe sounds much less like interstitial lung disease from an EGFR TKI than progression of the underlying disease. If there's significant question, a biopsy is certainly a fine idea. If the progression was quite rapid, it's possible that the disease now has transformed into small cell lung cancer, which can actually occur 3-14% of the time when acquired resistance to an EGFR TKI occurs.

-Dr. West

mmac
Posts: 2

Jim, this is one of the papers, but if you google the topic there are quite a few. This one notes that the FDA advises that Erlotinib should be stopped if ILD becomes evident.

Fatal interstitial lung disease associated with oral erlotinib therapy for lung cancer
Demosthenes Makris1, Arnaud Scherpereel1,2,4*, Marie C Copin3, Guillaume Colin1, Luc Brun3, Jean J Lafitte1 and Charles H Marquette1

* Corresponding author: Arnaud Scherpereel a-scherpereel@chru-lille.fr

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JimC
Posts: 2753

mmac,

I think the confusion here comes from the use of the term "interstitial metastatic disease". It's well known that tarceva can cause ILD (interstitial lung disease)., which is a potentially fatal scarring of the lung tissue. It isn't progression of the cancer. And you are correct, when ILD appears tarceva is stopped immediately.

If the radiology report indicates metastases, interstitial or otherwise, those are not "caused" by tarceva. More accurately, it's failed to effectively prevent them.

JimC
Forum moderator

Dr West
Posts: 4735

Exactly. You're really describing a pattern of progression of the cancer (sometimes called lymphangitic spread of the cancer), which is different from a hypersensitivity reaction to the EGFR inhibitor (interstitial lung disease).

-Dr. West