Hello, I am a family physician whose mother has been diagnosed with IIIb NSCLC. She may respond to Tarceva, but we elected to begin with standard Carbo-Taxol. We need to determine whether or not to add Avastin now after 2 cycles chemo, knowing that this decision would preclude enrollment in later clinical trials

S:72 y/o female, never smoker, non Asian with lingular IIIb poorly differentiated adenocarcinoma-large pleural effusion; primary tumor 2.5×3.5 cm; s/p 2 cycles Carbo-taxol, well-tolerated. Clincally stable. Has EGFR overexpression; further testing: EGFR mutation, KRAS, and T790u pending.

Minimal radiographic response (chest x-ray)after first cycle Carbo-Taxol.
She has a clear abdominal CT and brain MRI. Not on anti-coagulants. Has controlled hypertension and has a glomerular filtration rate of 45.

Decision needs to be made:

add avastin to chemo? (this would preclude later clinical trials)
complete 4-6 cycles chemo then enroll in SWOG036- trial Avastin/Tarceva? Begin Tarceva only now?
Begin clinical trial Avastin/tarceva now?
Consider trial Tarceva/Cetuximab after 4-6 cycles Carbo-Taxol?

-What additional testing/information would assist with decision?
-Would determination of whether there is a component of Bronchoalveolar carcinoma guide treatment decisions?
-Should decision making be guided by desire to ‘leave options open’ and not close the doors on clinical trial possibilities?
-Would tarceva/avastin be available even if Avastin is added to chemotherapy at this time?
-Would 2 cycles Carbo-Taxol be sufficient to determine whether or not there will be a response?
thank you

As a physician, I’m sure you can understand that I can’t give medical advice about what a particular person should do if they aren’t my patient.

I don’t think that any further testing is necessary, since this workup is already quite complete. The mutation testing is nice to have but isn’t a clear standard of care at this point, so the information you have is really over and above current standards.

It is definitely routine to check scan results after two cycles to assess response. I would consider a chest x-ray to be of some very slight value to determine a dramatic response or progression, but it provides incredibly less information than a CT, and most patients will have more modest results (good or bad) that require a CT to really clarify their response to treatment. And two cycles is generally sufficient to draw a basic conclusion of whether the initial treatment is leading to a response, stable disease, or progression. We would generally be inclined to change treatment for progression and often continue treatment for a response or progression, at least out to 4-6 cycles. That depends on the treatment being tolerable.

In my mind, a component of BAC doesn’t change things. BAC shouldn’t be poorly differentiated, so I wouldn’t believe any assessment that mentioned BAC and certainly wouldn’t let it guide any of my clinical decisions. Besides, we don’t yet have any clear evidence that we should be treating BAC differently from other NSCLC types. If I do, it’s based on the overall clinical picture and behavior of the tumor, not based on a pathologist’s terminology.

I personally favor maximizing treatment options, which does entail working around eligibility for clinical trials. However, these are very individual decisions to which it’s not possible for anyone to say what a particular patient “should” do.

There are certainly trials that have combined avastin and tarceva, and the combination appears to be safe. There isn’t evidence yet that the combination improves survival compared with tarceva or avastin alone.

Because it’s not really feasible for me to answer many, many questions for everyone, it will be helpful if you can prioritize and limit the number of questions. Many of these questions are judgmens that don’t have a clear answer, and I’ve covered aspects of several of them in the posts included in the subject archives for the lung cancer section:

http://cancergrace.org/lung/subject-archives/

Above all, I can answer general questions but can’t and don’t want to try to answer questions about what an individual person should do. My goal is to provide enough information to help enable patients and families make more informed decisions along with their own medical team. Please do feel free to raise questions about what we’d consider to be standards and optimal treatment, which are much more feasible for me than trying to answer a question framed as “what should I/mom/my husband/etc. do?”.

-Dr. West

Hi r1cardo, please accept my sympathy for your family’s ordeal. Truly cancer affects families as much as individuals, and the plight of the family member who is also a physician is unique since all of your other family members will expect you to know what to do when most people would just like to be a caring son in your situation.

I applaud your mother’s physican for sending the array of molecular tests (EGFR mutation, KRAS, etc). I am of the opinion that we should be routinely sending these on all newly diagnosed patients, especially non-smokers. Without commenting on your mother’s specific case, I am seeing a lot of never smoking NSCLC patients these days. Given the recently presented data from the IPASS trial (Iressa Pan Asia Study; presented at the IASLC Chicago Lung Cancer meeting in November 08), which indicated a superior survival for patients treated up front with an EGFR inhibitor (Iressa) in the subgroup with EGFR mutations, I think that all patients with confirmed mutations should eventually receive an EGFR inhibitor (in the USA this would be Tarceva). One interesting piece from this trial, however, was that patients with mutations who received chemotherapy up front seemed to do just as well as long as they got the EGFR TKI once their disease progressed. For this reason, I think it is reasonable to start chemo in cases where the mutation status is unknow (which is everyone until the test becomes more readily available) and reserve the Tarceva for later on.

The question of whether to hold back something so that it can be given later on (such as in a clinical trial) is a difficult one, but here is my general opinion. NSCLC is never more sensitive to treatment than right after diagnosis. Every time a therapy is tried and the patient progresses, the chances of a second, third, nth-line therapy controlling the disease gets worse, so holding back a therapy known to improve survival just to keep it available for later down the line might not make sense.

Pardon me for making a late comment to this article.

I recently read a nice briefing on Angiogenesis:
http://www.fbta.info/site/stacks09/angiogenesis.ppt

While the focus is on Brain Tumors, many of the slides offer some nice graphics and discussion of Angiogenesis in general (3, 9, 14, 33-34). Also, slides 39-40 clarify (to me) a concern about Avastin and increased invasiveness, which, in context, appears to specifically apply to Glioblastoma multiform (GBM).