Mixed Response after first line treatment in Stage IV NSCLC - 1252767

I just did a couple of videos talking about how we might approach a mixed response:

http://cancergrace.org/lung/2013/01/01/mixed-response-video/

and also the biology behind a mixed response:

http://cancergrace.org/lung/2013/01/07/biology-of-mixed-response/

If the balance is more in favor of moving to something else, then it makes sense to primarily focus on the treatments we'd approach for progression after first line for advanced NSCLC:

http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-o…

Good luck.

-Dr. West

I'm not sure exactly what you mean, but I think the answer is no. I would also say that very few, if any, expert lung cancer specialists put any stock in chemosensitivity testing that is marketed aggressively, but it doesn't include any evidence that people who do it live any longer than people who don't. Many tests are also quite hard to do on bone biopsies, which require harsh chemical treatments to decalcify the bone.

-Dr. West

This would be a marvelous advance in the treatment of nsclc or any cancer but it appears from your link that it's still in the early stages or clinical research. A bewildering number of promising treatments go into phase 2 clinical trials that don't go on to prove to be beneficial to people with cancer. The trial you mention had good results but seems to have had only 30 people in the trial. So I don't know how positive anyone can be with data from such a small group...other than move forward with more testing.

We'd all appreciate the treatment advances sooner than later but it's inspiring to know that our dedicated researchers are plugging away.

I hope this goes on to be more compelling than initial such tests.

I think Dr. Nagourney is a truly committed scientist, and I agree that it is promising. He also used wording that speaks of the potential of this work if it is validated in a larger setting. It is phase II research in one smallish patient group, which is subject to a very real risk of selection bias, as we have seen here over and over and over. If it is tested in a randomized trial that demonstrates that patients who undergo the chemo selection process based on their lab investigation do significantly better than patients who are managed in the best way we know how now (but not including the Rational Therapeutics protocol), I think it will be a real step forward. But these claims have been made for years and years and years, and we still have yet to see a prospective, randomized trial show that patients who undergo this kind of testing do significantly better. Meanwhile, the tests are marketed and often promoted by industry, patients, and caregivers who are selling a concept more than compelling evidence.

-Dr. West

There are different levels of evidence behind different markers trying to predict the efficacy and safety of lung cancer drugs. Here's my opinion (note word choice) on our current state of affairs:

BEST EVIDENCE:
*EGFR mutation- People with mutation have high probability of response to tarceva
*ALK rearrangement- People with rearrangment have high probability of response to crizotinib
*Non-squamous histology- People with nonsquamous NSCLC have better responses to pemetrexed than SqCC
*Non-squamous histology- Avastin is safer in people with nonsquamous NSCLC

VERY PROMISING:
*ROS1- People with rearrangment have high probability of response to crizotinib

PROMISING:
*ALK rearrangement- High probability of response to HSP-90 inhibitors.
*KRAS- Perhaps high probability of response to HPS-90 inhibitors and MEK inhibitors.
*MET- Overexpression may predict for efficacy of metmab.
*Squamous histology- Patients with squamous histology may have superior response rates to abraxane, but not superior survival
*Elderly- Elderly patients may have superior survival with abraxane

MAYBE:
*BRAF- Mutation may predict for efficacy of BRAF inhibitors
*ERCC1- Proposed marker for platinum sensitivity
*RRM1- Proposed markert for gemcitabine sensitivyt
*TS- Proposed marker for pemetrexed sensitivity

DATA UNIMPRESSIVE THUS FAR:
*A variety of expensive assays claiming to predict which chemo will work.

With a terrible cancer like lung cancer, it is natural to want to shoot for better results than those found with standard chemotherapy. I agree with this feeling--I've dedicated my life to lung cancer research out of a dissatisfaction with our current standards. But, in my opinion, we should look to data to say which things are most promising. And, when new unproven therapies are tried, we should keep track of the results so that we can learn what really works. To me, this means clinical trials.

The treatments we have for bone involvement are really the chemo or other systemic anticancer treatment (like a targeted therapy of Tarceva, for instance), the Zometa (zoledronic acid) or XGEVA (denosumab) you mentioned, and radiation to treat the pain of a painful metastasis and reduce the structural instability in a bone metastasis at risk of fracturing. Occasionally a surgery is done to stabilize a bone, but that really rounds out the list of what there is.

There are a couple of ways that the term "palliative" is used. One is just "non-curative", and really by definition, nearly all treatment of metastatic lung cancer is palliative. The goal is often to prolong survival, sometimes by a lot, but we can't offer the promise of a curative intervention. The second definition means "to reduce symptoms and maximize quality of life", but that is just in addition to whatever else we might do. It's not a consolation prize that is code for "ineffective token therapy".

-Jack

From experience, he will continue with chemo after radiation is completed. Mutually exclusive probably meant they'd be done separately and not concurrently. Take care, Judy

Chemo is typically suspended during the radiation in this setting, and it may be interpreted that the chemotherapy used up to now is not effective because the new lesions are evidence of progression on this treatment. So it would be typical to consider subsequent, often different, chemotherapy or other systemic therapy following completion of the palliative radiation.

Good luck.

-Dr. West

jmark,

Given an interest in experimental trials, if he is still fit enough for one, you might be interested in determining the driving mutation of the lung cancer. Occasionally a trial for useful one looks promising (though more often not).

Since there is a history of smoking years ago and you've already tested EGFR and ALK, you'd probably test next for the not-so-useful-yet KRAS (very common in smokers, uncommon in never-smokers).

If KRAS is the one, there are some clinical trials for that. Not many too promising yet, but there might be a couple okay ones and we'll probably hear more about them in June (big ASCO conference). (In the meanwhile, I think a recent trial suggested selumetinib added to chemo might improve response a bit.)

If triple-negative for KRAS, EGFR, and ALK, there's still a chance it could be driven by a rarer one. The odds of something useful aren't high, but might worth a shot. Ask your oncologist.

ROS1 is the one I have, with good results for me for 1-1/3 years so far. ROS1 is mostly in younger never-smokers, but there are exceptions -- some early data found 10% of ROS1 in smokers, and found ROS1 even in a 70-something patient. So the odds for this very rare one would be small, but maybe worth a shot.

RET is another potentially promising one, but I have yet to see any research results on it. RET, too, is more common in younger never-smokers, probably with exceptions, too. (RET trials borrow drugs for RET-driven thyroid cancer.)

There's also MET and HER2 and BRAF, though I'm not sure how well those trials are doing.

And if the driving mutation isn't a useful one, for when chemo options stop being useful you might ask your oncologist about any other "promising" trials. (Be sure to discuss travel preferences or limitations -- the best trials usually aren't local.) BTW, I'd always ask for the odds of shrinkage or stability from a trial drug, & how long.

Best hopes,

Craig in PA

That's really great to hear. It's wonderful he's responding well and has had a turnaround in his outlook.

Just so you know, Procrit is associated with a modestly reduced survival, so it has become a lot less commonly recommended in recent years, as evidence has mounted that in cancer patients, it can have a detrimental effect on survival. I suspect the oncologist reviewed this, since it's part of a rather elaborate consent process for Procrit nowadays.

-Dr. West

Here's what Dr. West has said previously regarding chemo brain vs. brain met symptoms:

"there's a huge amount we still don't know about chemo brain. Here's an article from the NY Times this week that asks whether the suspected side effects of chemo are actually more attributable to the underlying cancer:

http://www.nytimes.com/2010/10/12/health/research/12mental.html?_r=1&re…

One thing I'd add that may be reassuring is that subtle (or not that subtle) memory problems and word-finding aren't as typical of brain metastases as symptoms like balance problems/falling, vision changes, headaches, nausea/vomiting, and seizures."

I hope these symptoms are a temporary effect and clear up soon.

JimC
Forum moderator

Chemo brain is really more subtle than that...not really slurred speech but problems keeping track of plans, making associations with words, etc.

Sometimes metabolic issues can be a culprit, which might be detected with a blood test looking for salt imbalances or other problems that might be readily reversible.

Alternatively, a CT of the brain isn't quite as detailed as a head MRI but would still be a fine way to screen for a brain lesion that isn't extremely subtle. It's still a fine test and is a lot less to go through for people averse to an MRI.

Good luck.

-Dr. West