Treatment Options for Late Stage NSCLC - 1289023

Sat, 10/29/2016 - 09:43

Diagnosis - NSCLC adenocarcinoma and positive for 858R EGFR and negative for 790M., MET, ALK, PD-1, PD-L1 and KRAS by the Oncomine test.
Prior treatments - Carboplatin/pemetrexed with 20% tumor shrinkage; Tarceva for 3 months with additional 25% shrinkage then significant progression; currently on 5th cycle of Opdivo with stability shown in third cycle scan.
Possible future options - The oncologist is considering Tagrisso even though 790M negative/EGFR positive. Can you comment on the efficacy of Tagrisso in 790M negative and EGFR positive patients? Can you suggest other options for future treatment?
Thank you in advance.

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Hi, just wanted you to know we will get to you question in the next hour or so. So sorry for the delay.



Hi afi203,

Welcome to GRACE. It's good to hear that Opdivo is showing good results, and I understand your interest in being ready with future treatment options.

At this point it's not clear how well T790M-negative, EGFR-positive patients fare on Tagrisso. As Dr. West wrote a few months ago: "Third generation EGFR TKIs may prove to offer meaningful benefits to the 40-50% of patients with T790M-negative acquired resistance, or we may need to search for better options elsewhere." -

In that regard, however, has a new biopsy been performed and tested after the cancer progressed on Tarceva? From your post, it seems that the genetic testing was done prior to treatment. At that juncture, a T790M mutation would be a de novo mutation, one which is present from the start rather than one which developed after treatment. If there hasn't been a new biopsy, it is possible that the T790M mutation is now present.

Another question: did the cancer progress after the initial therapy with Carbo/Alimta, or did the change to Tarceva come after a prescribed number of chemo cycles without evidence of progression? When a patient stops a treatment to which they've responded and not progressed, it is reasonable to consider returning to that treatment. In this case, since repeating a platinum agent is not advised due to increasing toxicity, returning to pemetrexed (Alimta) could be considered.

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Thank you for your prompt response. Here are the answers to your questions.
The biopsy that was negative for the 790M mutation was done one month after the Tarceva treatment ended.
The cancer did not progress after the Carbo/Alimta treatment. The primary tumor shrank 20% with this treatment. The switch to Tarceva was made after four Carbo/Alimta infusions and as soon as the 858R mutation was discovered, not because of progression while on Carbo/Alimta.
Your point is well taken that a return to Alita is a possibility. I didn't mention in my post that there was a single infusion of Alimta/Avastin that was not tolerated, but that probably was a reaction to the Avastin as the Carbo/Alimta combination was well tolerated.
Do you have any additional comments now that you have this new information?


Hi Al,

In light of the biopsy results, I would think Tagrisso would be a less attractive option than standard chemo such as Alimta, Docetaxel, Gemcitabene or Navelbine. The first two of those are FDA-approved for second and later lines of therapy; the other two are approved NSCLC agents which haven't been as fully tested in that context.

Of course, I'm hoping that Opdivo will continue to show good results for a long time, and that there are additional options by the time any treatment change is warranted.

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