Standard of care after tarceva second line, NSCLC/adeno, rare EGFR? - 1263133

Hi bolu,

I don't think you can really say there is a "standard of care" at this point in your mother's treatment. In the U.S. there are three drugs which are FDA-approved for second (and later) line treatment - pemetrexed (Alimta), erlotinib (Tarceva) and docetaxel (Taxotere). That leaves Taxotere as the option which has been thoroughly studied and proven effective. Other drugs which are approved in first-line treatment and are also used in later lines of therapy include gemcitabene and navelbine.

So one option is to try another of these traditional chemo drugs. As you've noted, the other choice is a clinical trial. For a patient such as your mother, who attained stability from first-line chemo which was not long-lasting, Dr. West has summed up his thinking as follows:

"So the better the first line outcome with chemo, the more inclined I’d be to recommend more chemo; conversely, the more disappointing the outcome, the more inclined I’d be to recommend EGFR inhibitor therapy with tarceva, although in this case I’m selecting it as the “not more chemo” choice more than because it’s an EGFR inhibitor. I’d consider it more of a wild card, and a wild card is good when you’re expecting a bad outcome with what you’ve already got (for instance, more chemo), but it’s less appealing if you’re expecting a good outcome with what you’re holding."

In your mother's case, she did not respond to Tarceva, and her response to chemo was good but not great, it's possible to try another chemo agent but it may be better to try a novel agent.

As far as the list of mutations found in your mother's cancer, the problem is that for most of them there are no drugs which have been proven effective yet; they are in the very early stages of development and testing. So it is difficult to say that one trial or drug is better than another - we just don't know yet.

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Dr. Weiss has stated his thinking regarding the subject as follows:

"One thought, particularly if your cancer is adenocarcinoma (which I assume that it is based on alimta use) and if your smoking history is limited, is to pursue ROS1 testing. This would only really make sense if you’d be able to travel to one of the trial sites if found to be ROS1 positive (if you search ROS1 on GRACE, there’s lots to explain what I’m talking about).

Otherwise, you could really be seen at any major medical center that has trials. Typically, for fourth line, I often look to phase I trials for my patients. These trials tend to have the newest and most exciting new targets, although the skeptic could also argue (very reasonably) that they are the least proven therapies as well. My favorite kind of phase I trial for my patients would combine an agent with known efficacy against cancer with a novel targeted agent that I have some excitement about really helping." - http://cancergrace.org/lung/topic/clinical-trial-search/#post-11911

It really helps to have input from your own doctors, so you might want to consider a second opinion, preferably at the teaching hospital for an academic institution; their doctors tend to be well-informed as to the most promising trials available.

Good luck with the next line of treatment.

JimC
Forum moderator

First, I'd say that Jim is exactly right in his explanation of a complex issue. Taxotere (docetaxel) is the only agent remaining that has a proven survival benefit in previously treated patients with advanced NSCLC. While it would be reasonable to consider Navelbine (vinorelbine) or Gemzar (gemcitabine), Taxotere was found to be significantly superior to Navelbine when compared head to head, and Gemzar has been tested in 2nd line as well but has never demonstrated a significant survival benefit.

Cisplatin/Alimta (pemetrexed) is likely the most challenging of all of these options but is also a doublet and not a standard 2nd line treatment. Taxotere would likely be pretty universally ranked more challenging than Navelbine or Gemcitabine, but as the only agent with a survival benefit, I think it's important to clarify your goals. If you want to minimize side effects over using a more effective treatment, that's fine, but it's a bit like the drunk who lost his keys in the dark alley but is looking for them in the well-lit street because the light is better there. It's hard to serve two masters, especially as treatment options become more limited with ongoing therapy and a patient becomes weaker. It's perfectly fine to prioritize quality of life, but at some point if you are avoiding a more effective drug to give a less effective one that is easier, it's time to question why you are giving potentially toxic treatments with little probability of benefit and not focusing overwhelmingly on the patient's symptom management.

As for "chemo-brain", it is not well studied enough to say that any one agent or combination is a worse culprit than another. At this point, it is little more than a general observation by some patients that they feel a mental fog on chemo that they didn't notice before it. It hasn't really begun to be carefully studied yet, especially in lung cancer.

Good luck.

-Dr. West

Like Jim noted, I'm impressed that she seemed to do better with chemo than with an EGFR inhibitor, and the rare EGFR mutations often seem to do no better than people with no EGFR mutation when receiving EGFR-based treatments. I think the most appealing concept is some Taxotere-based chemo +/- novel agent trial, but there's no particular one that bubbles up as the clear top choice. Immunotherapy is always a provocative curve ball, but the limited evidence actually suggests that never-smokers tend to be less likely to be major beneficiaries of the immune checkpoint inhibitors (anti-PD1, anti-PD-L1) than current or former smokers.

Good luck.

-Dr. West

I agree with Dr West, except about the never-smokers. I have two never-smokers in clinic (one an EGFR mutant) this week who've had durable remissions on a immunotherapy PD1 trial. I think the never-smokers may have other reasons for doing less well on these type of trials, but there is no reason to think they won't work. I understand there are very limited data presented for one trial by Dr Spigel that suggested smokers were more likely to be PDL1 positive, but that hasn't been established yet. The proof is the pudding, and I have personally seen it work.

I certainly agree that the work on an association of activity of these agents with smoking status is very tenous, quite early at this point, so I wouldn't want to overstate it.

-Dr. West

The data are more established for Taxotere (docetaxel), but it's also a notoriously challenging treatment to deliver in patients with a marginal perfformance status. I find it exceptionally believeable and probably very wise to NOT pursue it in someone who is pretty frail, and in whom the risk of prohibitive toxicity and very possibly harm could easily exceed benefit.

In contrast, Taxol is less established but is a treatment that may be far more feasible to deliver safely. It is true that there isn't a proof of benefit, but that proof of benefit with Taxotere was in patients who were far more fit than your mother. And absence of proof isn't proof of absence, so the Taxol or some other agent could potentially be effective.

It's an appropriate place for such a judgment call, in my estimation.

Good luck.

-Dr. West