Testing Beyond KRAS Positive Determination - 1268373

Wed, 02/04/2015 - 13:47
nanknits
Posts:

Now that I am no longer in the MPDL3280A immunotherapy trial and have restarted Alimta, this time without Avastin, I am back to thinking about treatment beyond Alimta.

The analysis done in 2010 of tissue from my 2010 lobectomy indicated EGFR and ALK mutations negative and KRAS positive. Is there any reason to believe repeat analysis of the original tissue would yield a different answer?

Or that analysis of fresh tissue, if obtainable, would come up with a different result?

Am I correct in thinking that being KRAS positive precludes the presence of any other actionable cancer driver?

Would it be useful to identify my KRAS sub-type?

Nancy

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JimC
Posts:

Hi Nancy,

I'm sorry that the trial didn't work out for you. I don't think re-testing the original tissue would yield a different result, but it is possible that it could be tested for a mutation that was not looked for back in 2010, especially if there is a trial of an agent targeting that mutation. Testing new tissue would not likely show different results for EGFR or ALK, but if you get new tissue and you're going to test it would make sense to test that newer tissue so you know what's going on right now.

JimC
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Dr West
Posts:

You're right that a KRAS mutation is usually not seen with other mutations, though a small minority of cases break that rule.

In (early) 2015, there is no clear value to looking at the specific KRAS mutation -- there is no role for this level of granularity in clinical management, and it isn't felt to have any reliable clinical implications that would direct/inform decisions in treatment.

Good luck.

-Dr. West

carrigallen
Posts:

If the KRAS is positive, there is usually no need to keep testing for other actionable markers, unless it is part of a clinical trial or study. So more testing is unlikely to change what your doctor does.

nanknits
Posts:

As mentioned earlier, I started in an MPDL3280A immunotherapy trial [Birch] in Sept, 2014, and after 6 cycles was taken off the trial in January, 2015, due to persistent but modest progression of two lung nodules. The trial onc decided MPDL3280A was not working and that I was not experiencing pseudo-progression. I immediately began alimta alone on January 19..

A scan on March 2, 2015, after two alimta cycles showed about 20% shrinkage in nodule size but a scan on April 14, 2015, after the next 2 alimta cycles showed only "relative stability".

Is it possible that the shrinkage after 2 cycles of alimta was due to the 6 cycles of immunotherapy and not the alimta?

My eight prior chemo treatments [carbo + alimta + avastin x 4 and alimta + avastin x 4] achieved only stability, never shrinkage. The only time there was shrinkage was following 6 cycles of immunotherapy.

Even if the trial onc is right about MPDL3280A, would other immunotherapy drugs, perhaps Opdivo, be a reasonable treatment option if I am eligible?

Nancy

catdander
Posts:

Hi Nancy,

I'm so sorry this is working out in such a confusing way. I know I'd be asking the same questions. This is such a young type of drug I wonder if we have good enough answers yet. I'll ask a doctor to respond.

I hope you're feeling alright physically and I hope you're holding your nerve well enough to enjoy living life. Thinking of you often.

Janine

nanknits
Posts:

Hi Janine-
Glad to hear from you. Yes, I am feeling pretty good except for days 3-7 following an alimta infusion. I have had 6 since Jan 19 and it seems like the side effects are somewhat more of a knockdown each time and the 7th is scheduled for next Tuesday. But I know it could be a lot worse as alimta side effects are relatively mild.
I bet with the onset of summer your quilting is not getting a lot of attention. My knitting is sort of on the back burner, but not always.
Nancy
PS Please tell me if I am not following the rules for using CancerGrace. I am not confident that I am.

Dr West
Posts:

While it's always possible, it sounds to me like the sequence of events is correct: the shrinkage came coincident with the Alimta, after there was what was concluded to be convincing progression on MPDL3280A. The evidence suggests immunotherapy didn't work and that chemotherapy did. This is actually not so hard to believe.

There is no evidence of responses to one immune checkpoint inhibitor after someone has progressed on another. This is essentially unstudied, but I would consider these agents to be similar enough in mechanism that I would not expect to see a strong response to nivolumab after progression on MPDL3280A.

Good luck.

-Dr. West

carrigallen
Posts:

I would also add that with anti-PD(L)1, the 'pseudo-progression' with subsequent durable response is remarkably rare, maybe 1 in 100 non-small cell lung cancer treated. Like many things, it is vastly overstated. If the first scan shows enlargement, we repeat the CT scan in 4 weeks, and if the enlargement persists, we can be fairly confident that the PD(L)1 drug is not helping, and a different treatment should be considered.

nanknits
Posts:

Thanks Drs West and Creelin. Your thoughts reassure me that stopping the immunotherapy was the right thing to do.
Nancy