Progression on Crizotinib, upcoming lung radiation, continue crizotinib? - 1272162

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southsidegirl69
Progression on Crizotinib, upcoming lung radiation, continue crizotinib? - 1272162

After over a year on crizotinib, a week ago my CT scan showed my lung nodule has increased by 1 cm in 8 weeks to 3.0 cm. and the PET showed that it is now an active lesion. And also, 3 small brain mets were discovered in September, so in October had the mets radiated. So, I have acquired resistance. As of now all that's left is this original lung nodule, which never really decreased in size much at all while on crizotinib, but basically remained unchanged. Radiation to the lung is now scheduled for the end of December. I am still taking crizotinib, and will go off temporarily during radiation treatments. Than advised to go back on crizotinib upon completion of the lung radiation. The question is, after completion of radiation to the lung nodule, would crizotinib still be the best treatment to stay on, even though it no longer kept the lung nodule from progressing and I had gotten brain mets? Some of the posts and videos suggest moving on to a different drug. But I did not find anything saying to stay on crizotinib after acquired resistance and disease progression. Thank you.

Dr Pennell
Dear southsidegirl, thanks

Dear southsidegirl, thanks for sharing your story. You confusion is certainly understandable, this is a rapidly changing field and there isn't always agreement on the best approach. Sometimes there are several reasonable options, and personal preference and your doctor's experience with one or the other may make a big difference.

Should someone switch from crizotinib when they develop acquired resistance? For widespread progression the answer usually is yes, and there are (as of today) now two approved drugs available outside a clinical trial: Xykadia (ceritinib) and alectinib which was approved today. Both have also shown activity in brain metastases which is a welcome benefit since brain mets are so common in ALK+ patients.

For limited progression in one or a few spots, sometimes called "oligoprogression", an alternative approach is to remove or radiate the progressing spots, and limited studies have shown that patients can remain on crizotinib longer before having to switch to a new drug. The idea is the radiation wipes out the resistant cells while the crizotinib remains effective on the rest of the cancer. No one knows yet if they will actually live longer with this approach, but it has become quite common and I tend to recommend this myself when I have patients in this situation. It sounds like this is what your doctor has in mind.

I tend to think of treating ALK+ lung cancer as a marathon and not a sprint, and I try to stretch out the length of any one treatment as long as possible before moving on to the next option. This isn't the right choice for every situation though and sometimes switching drugs is definitely the best option. I can't say which is best for you, but this is at least what the doctors think about when we try and decide what to recommend.

Best of luck!

southsidegirl69
Dr. Pennell,

Dr. Pennell,
Thank you so much for your rapid and informative reply. At least being ALK+, there are now 2 approved drugs that are possibilities to move on to. Glad to learn that alectinib just approved today, exciting times! Love your analogy of ALK+ being a marathon, not a sprint. Thank you for your work, and for responding to the many questions we all have on this journey to health.