25mg Tarceva enough & better? - 1262351

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donaldl
25mg Tarceva enough & better? - 1262351

This is my 1st posting on Grace. My wife (43 years old Asian) has been confirmed as stage 4 adenocarcinoma on April 2013 and no lymph node involvement fortunately yet but mainly metastasis to pleura.. After 8 month of chemo & maintenance (Avastin and Pemetrex) it metastasized to small nodules on both lungs (<5mm) so we switched to Tarceva 100mg daily & in 25 days it resolved these small lung nodules! However after 35 days into Tarceva she developed severe skin rashes (grade 3+/4) and we have to stop Tarceva for 21 days and now she is back for the 4th days but now only with 25 mg daily.... I read some paper from J Thorac Oncol. 2010 July ; 5(7): 1048–1053 titled "Erlotinib at a dose of 25 mg daily for non-small-cell lung cancers with EGFR mutations" by Wee-Lee Yeo et al from Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA & Cancer Science Institute, National University of Singapore, and the conclusion is in laymen's terms, if you are EGFR positive according to their study on 7 patients, just 25mg Tarceva daily should be enough as it gives the drug concentration in blood serum of the same concentration as previously approved for Iressa (the predecessor of Tarceva), and that since Traceva & Iressa work very similarly 25 mg should be good enough. So, three questions from me below appreciate your answers/feedbacks:
1. 25mg Tarceva daily should be enough for some patients --- do you have any experience and stories in this dosage? I would love to hear from you as I know some are taking 25mg daily.
2. would this low dose PROLONG the "inevitable" total drug resistance time as it decreases the OVERALL total dose taken by the patient's body?
3. My wife is NOT EGFR positive, but the Tarceva works very effective for her in just 25 days! Would the insurance approved her for next gen. TKI drugs such as Afatinib with other combo? Please kindly advise. Thanks so much and God bless, Don

Dr West
Reply To: 25mg Tarceva enough & better?

Our general approach is to give people the highest dose (up to the standard dose of Tarceva (erlotinib) of 150 mg daily) that people can tolerate well enough to continue on longitudinally. However, many of the people with an activating EGFR mutation are extremely sensitive to both the beneficial effects and side effects of EGFR inhibitors and need significant dose reductions. Many of my best responders for years have required dose reduction to 100 mg/day or less, and some 50 mg/day or less. I have patients who have done well for a very long time on 25 or 50 mg daily. That said, I don't presume that's the optimal dose for everyone with an EGFR mutation and work down from the standard dose, depending on tolerability.

I don't think there's any reason to think that dose reduction will delay acquired resistance. There's reason to think there's a threshold effect and that a little may be enough for many patients, but I wouldn't aim low as a specific strategy.

As for your wife's response, I just described a similar case of mine:

http://cancergrace.org/lung/2014/01/11/molec-oncolfallibility/

She's responding as if she has an EGFR mutation, and if she's an Asian never-smoking or minimally smoking woman responding very well to Tarceva, I strongly suspect her cancer actually has an EGFR mutation, whether it was detected or not. The absence may be because the test missed it, or because the sample of tumor tissue didn't happen to harbor it, but it might be helpful to repeat a biopsy in a case like hers, provided there's something you could actually do with that information, like pursue a trial for acquired resistance that is only available to people with an EGFR mutation.

I hope that helps.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

donaldl
Reply To: 25mg Tarceva enough & better?

Dr. West you are TERRIFIC !!! You answered almost all of my questions --- yes she is an Asian never-smoking 42-yr old young woman and none of my family smoke & no family history of lung cancer...(except we found out later a female cousin on her Dad's side had stage 1 NSCLC 7 yrs ago) Also her stage 4 NSCLS adenocarcinoma diagnosis was done after biopsy and is what some Korean doctors called "dry pleural dissemination" as she has no pleura effusion and the primary tumor is 3.5x2.5 cm2 but metastcized into pleura on the right lung and a small nodule on the chest pleura (<5mm) and apparent no lymph node involvement still. No metastasis on other organs either (her PET Scan max. SUV was only 2.2 last Nov.), but last Dec. we saw those multiple nodules on both lungs (<5mm) highly suspicious of metastasis and that is why we switched to Tarceva, even though her oncologist initially suggested Taxotere but I was agreeing with you that Tarceva should work for her just like what you stated in your blog! They could have missed it in the Lab (they expedited the EGFR test as we pushed them to get Tarceva prescribed and approved for us last April but couldn'), or the tissue did not happen to harbor the mutation --- thank God I insisted on Tarceva but not Taxotere and the oncologist OKed it and the insurance approved it this time! Now sorry my 3 more questions,
1. I assume you must have you seen patients with this "dry pleural dissemination DPD" even though our oncologist seems to be unaware of it --- does this group of patients have a rather different overall response or disease progression?
2. In the Korean study (on J. Radiology http://pubs.rsna.org/doi/full/10.1148/radiol.11110053), Dry Pleural Dissemination patients has a ~x3 longer time overall survival rate (OS) prognostic than patients with pleural effusion; would your experience corroborate on that? Please kindly advise.
3. Have you had any of those patients with DPD responding to Tarceva? Thanks so much and God bless

Dr West
Reply To: 25mg Tarceva enough & better?

I think these patterns are unusual enough that I don't draw any meaningful conclusions of what to expect from any prior publications. I think it's 100x more important to see what the patient's cancer is telling you: if the person is responding well, that's the most valuable piece of information.

I do have a patient or two with this pattern each year, but I don't track them separately, though as I think about them, they have tended to do unusually well. The diagnosis of dry pleural dissemination fits under the staging category of IVa disease, which is limited to the chest, as opposed to stage IVb, which is metastatic disease outside of the chest. Stage IVa tends to be associated with a more favorable survival.

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

donaldl
Reply To: 25mg Tarceva enough & better?

Thank you so much again Dr. West !!! Yes we do need all kind of good luck...... I think you must be right that it's x100 times more important to see what my wife's cancer is telling us with the responses, instead of drawing conclusions from prior publications... It is comforting to hear that you have seen these unusual patterns, and occasionally you do have patients with DPD & those patients with DPD tends to do unusually well.... We pray that God would have mercy on my wife and our family.... Again, we thank you SO much for your wonderful, wonderful help and service and consultation! God bless, Don

donaldl
Dear Dr. West,

Dear Dr. West,
How are you doing? Happy New Year 2015 ! Thanks so much for your kind, faithful and excellent service for the lung cancer patients and families! I have not posted here for almost a year now, which means the <50 mg/day dosage of Tarceva my wife is taking was working fine for her stage 4a NSCLC until now ---- however, we just came back from MDA and found that there are some 3-4 nodules in both of her lungs grew slightly in the past 6 months, and the largest one grew to the range of 5 mm (i.e., 0.5 cm). There is no new nodules though. Our oncologist used the wording that she is "disconcerned" at this point, but ask my wife to increase her Tarceva dosage to as much as she can tolerate. My wife has been taking ~50 mg per day for the last 3 months, but before that she has been taking ~ 25 to 40 mg per day.Since she is only 44 so the cells will grow faster in general than the older patients, 50 mg per day seems to be too low to me, don't you think? Please kindly advise. Thanks much! We are trying up to 75+ mg/day.

Also the growth seems to be all from the 3-4 nodules that were present in Jan. 2014 right after we saw this major response to Tarceva (even though she is EGFR negative) - i.e., the growth is from the old small existing nodules since 1 yr ago. Since my wife is not currently eligible for any clinical trials at MDA and also her nodules are too small to biopsy, our oncologist told us this is not Tarceva resistance, and this slight progression could just be a drug delivery issue with low dose. What do you think? Please kindly advise. Thanks!

My last (3rd) question is that I agree with you she may be EGFR positive, but we would not know about this yet. How fast do you think the new 3rd Gen TKI AZD9291 and the anti-PD1 immunotheraphy drugs will be on the market for NSCLC adeno patients like my wife? Our oncologist indicates that there might be new FDA approved drugs coming up in ~3 months commercially- what do you think? Please advise.Thanks much!

Dr West
There is no evidence that the

There is no evidence that the growth rate of cancer cells is a factor of age. I think it makes sense to take a daily dose of Tarceva (erlotinib) that is on the higher range of what is truly tolerable. I have a rare patient who demonstrated mild, indolent progression on a rather low dose and then seemed to be more stable on a modestly higher dose.

We don't know the time line for the third generation EGFR inhibitors or the immune checkpoint inhibitors, but I think a three month time line is not realistic. If it's 2015, I think it will likely be the tail end of the year.

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

donaldl
Dear Dr. West, Thank you SO

Dear Dr. West, Thank you SO much for your quick and wise and caring response! We saw your reply to my post last night within just a couple of hours of my posting --- thank you SO much again and you are just incredible! You answered all my 3 questions wisely! :)

Now I also think you are correct that my wife most likely is EGFR positive, even though her 1st biopsy test did not show it. Therefore, if her disease started to progress down the road (God forbid!), which/what clinical trials and/or treatment would you recommend in general ? We appreciate and value your expert opinions tremendously as we will go back for the 3 month check up after the increase of Tarceva for brain MRI and CT! Thanks so much!

Just to calibrate a little, because of the Lord's mercy my wife still shows no metastasis outside of her chest area, with no lymph node involvement nor any other visible radiographicmetastasis on the brain or other organs. She was diagnosed as stage 4 because the dry pleural dissemination (small nodules on the pleura of the right lung and 1 on the right chest pleura). Thanks so much again and God bless! Don

catdander
Hi Don,

Hi Don,

I've pasted a couple of links below that show the thought process lung cancer specialists use at acquired resistance however specific recommendations aren't possible because we hope it will be a long while before it's needed and options are changing.

http://cancergrace.org/lung/2014/10/08/ar_forum_after_1st_line_targeted_...
http://cancergrace.org/lung/2014/09/01/iaslc_oxnard_help_egfr_treatment_...

I hope this helps,
Janine

Dr West
I would sat that the most

I would sat that the most promising agents in this setting are rociletinib (CO-1686) and AZD9291, both third generation EGFR inhibitors. They are each being tested primarily in patients with a T790M mutation in the setting of acquired resistance, so she'd need to do a repeat biopsy to identify both an original EGFR activating mutation (exon 19 deletion or L858R substitution on exon 21) and the T790M mutation as a presumed cause of acquired resistance (seen in about 60% of cases of acquired resistance).

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education