Cetuximab-based treatment of metastatic anal cancer

Thank you for posting this.

Martha

I have cut and pasted the article in the link to make it easier to follow my questions:

Abstract

I don't get it, my poor brain is more mush than I thought.  It says that anal cancers all have EGFR and none have been reported with KRAS mutation.  It then goes on to say that 2 out of the 7 did indeed harbor KRAS mutations and they had progressive disease on the cetuximab.  I thought progressive meant that the tumors get bigger, despite the treatment, but the conclusion was that: Cetuximab-based treatment appears to be a valuable treatment option for patients with metastatic KRAS wild-type anal cancer.

I'm serious, what am I missing here?  Is progressive disease actually a good thing?  and how do you know or find out if you have KRAS mutations?  I had Foundation One genetic testing done and they didn't mention anything about EGFR or KRAS or anything else that I recognized, all my mutations were totally obscure.  I'm not usually this obtuse, but if you have answers for me, please keep it simple!

Carol

Cazz said:

Um

I have cut and pasted the article in the link to make it easier to follow my questions:

Abstract

BACKGROUND:

No standard chemotherapy regimen can be defined for patients with metastatic squamous cell carcinoma of the anus due to the low incidence of this disease and the high cure rate of localized tumors. Anal cancers universally express the epidermal growth factor receptor (EGFR) and KRAS mutations have not been reported in anal cancer thus far.

METHODS:

We report on 7 patients with metastatic anal cancer treated with cetuximab - a chimeric antibody against EGFR - on a compassionate use basis along with the results of KRAS mutational analysis.

RESULTS:

Marked tumor shrinkage was noted in several patients using cetuximab monotherapy or cetuximab/irinotecan combination as first or subsequent treatment line (usually after failure of cisplatin-based regimens). Two out of seven patients harbored KRAS mutations. Both patients had progressive disease receiving cetuximab, while the remaining 5 patients had either a partial remission (n = 3), a minor remission (n = 1) or no change lasting > or =6 months after previous rapid tumor progression.

CONCLUSION:

Cetuximab-based treatment appears to be a valuable treatment option for patients with metastatic KRAS wild-type anal cancer after failure of or as an alternative to cisplatin/5-fluorouracil-based therapy.

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I don't get it, my poor brain is more mush than I thought.  It says that anal cancers all have EGFR and none have been reported with KRAS mutation.  It then goes on to say that 2 out of the 7 did indeed harbor KRAS mutations and they had progressive disease on the cetuximab.  I thought progressive meant that the tumors get bigger, despite the treatment, but the conclusion was that: Cetuximab-based treatment appears to be a valuable treatment option for patients with metastatic KRAS wild-type anal cancer.

I'm serious, what am I missing here?  Is progressive disease actually a good thing?  and how do you know or find out if you have KRAS mutations?  I had Foundation One genetic testing done and they didn't mention anything about EGFR or KRAS or anything else that I recognized, all my mutations were totally obscure.  I'm not usually this obtuse, but if you have answers for me, please keep it simple!

Carol

The whole genetic mutation thing is of interest to me but unfortunately I don't understand it either. (Also, today is much a day of brain mush for me as well so will need to get back to you later, but I think......)

It was explained to me a while back that the KRAS mutation is more or less a predictor of whether one with EGFR would respond well or not to a particular drug....in this case Cetuximab. So, I think what this means is that all studied had EGFR, but only a couple "could have potentially been predicted to respond or not" based on the fact that those couple also had the bio-marker KRAS. This means that if KRAS is first detected, a wise choice for treatment may not be Cetuximab since those are the ones that went on to have progressive disease. (I could be way off, but thats my understanding right now)

I also remember hearing of some relation between squamous cell carcinoma, which is most common, and adenocarcinoma, and genetic mutations, but can not clearly recall what I was told. I think it was that the KRAS marker was more often found in adenocarcinoma????

As I said, I will get back to you after some checking but thats all I have for now, sorry.

katheryn