If Lorlatinib doesn't work?

Portal Forums Lung/Thoracic Cancer ALK Inhibitors If Lorlatinib doesn't work?

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February 12, 2017 at 2:23 am  #1290044    


Stage 4 age 39 March 2011 (very advanced stage 4b). 1) Alimta/carbo + radiation. 2) Erlotinib 3) Carbo/alimta again. 5) GK to brain and FOUND ALK 2013 7) Xalkori 6 months 8) Alectinib trial 3.3 years 9) More GK and about to start Lorlatinib

Current Issue:
We are now about to start Lorlatinib for simultaneous progression to brain and chest. Had GK to over 20 brain mets last week due to symptoms. Rapidly and aggressive advancing disease(always has had). Always had bulky disease in chest with little leeway for progressive disease.

If Lorlatinib is unsuccessful with limited time to make decisions what would be your next steps?
He has not had Ceretinib (is there any point to this?) …
If we can biopsy what you test for? Only ALK related or others?
If we can’t biopsy what salvage would be best chance walking blind… chemo or immunotherapy?



February 12, 2017 at 9:44 am  #1290047    
JimC Forum Moderator
JimC Forum Moderator

Hi Jo,

Welcome to GRACE. I’m sorry to hear of the new progression after so many years of treatment. At this point, there really isn’t a clear treatment path after lorlatinib. Dr. West has previously written that: “There also isn’t any real evidence yet that other second generation ALK inhibitors work after Zykadia [ceritinib].”http://cancergrace.org/lung/2014/04/30/new-approval-for-zykadia-ldk378ceritinib-in-alk-positive-nsclc-why-it-matters-even-if-youre-not-alk-positive/ And in another post, he stated that he hadn’t used lorlatinib (as of January 2016) since it was still an investigational agent. In light of this statement, it may just be too early to know whether one of these agents is likely to be effective after use of the other, and which sequence would be preferred. Of course, if options are limited, it might be worth a try.

Standard chemo would certainly be a leading option, especially since he hasn’t had it for quite a while, and the only non-platinum agent was Alimta. Docetaxel (Taxotere) is approved here in the U.S. as a second- and later-line agent, and Taxol, Abraxane, Gemzar and other agents also have activity against NSCLC. Immunotherapy is a possibility, keeping in mind 1) only about twenty percent of patients respond well to it, and 2) in comparison to chemo it can take longer for immunotherapy to show results, which can be an issue if there is rapidly progressing disease.

You can test for a broad range of mutations, but the only ones which currently have practical value are those for which there are targeted agents. With that in mind, the patient and oncologist may want to identify a particular agent under consideration (perhaps one being tested in an available clinical trial) and test for the appropriate mutation.

I hope that lorlatinib is effective for an extended period, allowing time for more information to develop and new agents to appear.

Forum moderator

Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

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