Advice needed: second line progression with Clovis (CO-1686), what now? - 1270445

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Advice needed: second line progression with Clovis (CO-1686), what now? - 1270445

Are you showing resistance to Clovis (CO-1686)? What is your treatment now?

What are the avail options out there? I appreciate any advice anyone has.

Has anyone gone back to Tarceva? What about Afatinib?

My dad, Dx'ed with stage IV NSCLC, completed 5 cycles of Clovis (CO-1686 500mg) as a second line treatment, just had a scan today (7/9/15), and the results were not great. His first line treatment was with Tarceva + chemo (Alimta+Carbo, then Alimta for maintenance).

There's cancer progression, with the main hilar mass in his RUL, measured at 32mm on 5/28/15 (after completing 3 cycles and stable in 2 previous scans while on the trial), and now 39mm today. His Onc at Cedars-Sinai is stopping the trial and is now planning the 3rd line treatment, with the following options:

1. Standard: (a) Docetaxel (taxotere) chemo

2. Phase-1 clinical trials:

(a) Focal Adhesion Kinase Inhibitor (FAK) --
(b) Combined PI3K/mTOR Inhibitor --

I have zero knowledge about these 2 trials, so I'll be researching these. But I would love to hear if anyone has any advice for me.

I am also considering getting a second opinion at a different facility, like City of Hope. Can you recommend an oncologist?

We discussed with his Onc two other trials, but he didn't qualify:

3. Peregrine, a form of immunotherapy, a randomize trial with 50% patients on Docetaxel (taxotere) + placebo and the other 50% on Docetaxel (taxotere) + a drug called Bavituximab (attacks blood vessels and activates the immune system). Do not qualify because it's only for patients who just had std chemo, and is a 2nd line treatment, and also, more importantly since the drug attacks the blood vessels, the main tumor is "very close" to one.

4. Anti-PDL 1? but it's for first line treatment...patients with no prior therapy.

Thank you and take care,


Hello Tom and welcome to

Hello Tom and welcome to Grace. I'm sorry your dad is going through this.

Trials always promise hope for new discovery, both for your dad and others who benefit from others who pass his way in the future. So your dad could enjoy contributing to others in moving into a trial option.

PD L1 is available only through trials for those with non squamous at this time but is thought to get approved be FDA by the end of the year. It is appearing that there needs to be a high expression of pd l1 in the body for the immunotherapies to be effective for those with non squamous nsclc. It can be prescribed but insurance doesn't pay and the cost is prohibitive at around 13,000 us$/month.

If your dad didn't progress on alimta it may be an option to move back to it. Historically once a drug has been tried doctors don't go back but there are those who have with drugs not progressed on with some success, alimta seeming to be one of the more successful ones.

Also tarceva, if your dad didn't progress on it perhaps it's possible to move back for another try. Usually CO 1686 is tried after tarceva stops working so there is no data showing if CO 1686 stops working so will tarceva.

Afatinib is a possibility while it was FDA approved it hasn't shown to have much added benefit passed tarceva though the added side effects are noted.

Taxotere is the next approved standard option.

Is good to have options though so so difficult to make. One thing to know is that after the decision is made the stress level drops dramatically...good to know.

We have lots of info on each one of these subjects and I encourage you to use our search engine and browse for more in-depth info.

Best of luck and hopes,

Janine, thank you for your

Janine, thank you for your post.

For first line treatment, my dad was on Tarceva for 4 wks, then Carbo+Alimta were added for 4 rounds, then just Alimta maintenance for 8 rounds, all while on Tarceva. Then he started showing progression.

For 2nd line treatement, he acquired the T790m mutation. He didn't quality for the AZD9291 trial, because the exclusion then was that you can't have more than 1 round of chemo. So he started CO-1686 for 5 cycles, until progression with yesterday 7/9 scan.

Now we're looking at 3rd line treatement, and I stumbled across the AZD9291 Expanded Program (, which I have already emailed his Onc about it.

On that website, it talks about the trial being conducted in FL and HI and we live in Los Angeles. But I also read about the Expanded Access Program through the FDA website ( where his Onc can submit an application to get my father into this trial. But I don't know if that means he can stay at Cedars-Sinai where he's currently being treated now and get in the AZD9291 trial, or what?


Hi Tom,

Hi Tom,

Yes, the drug would be shipped from the manufacturer to your own oncologist, who would administer the drug to your father. He wouldn't necessarily be "in the trial" but he'd be receiving the same drug as the trial participants.

Good luck with the application.

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JimC, thank you very much for

JimC, thank you very much for the clarification. I will be follow-up with my father's Onc.

What is your advice on getting my father on Afatinib, or a re-treatment of Tarceva, others? He's currently is not on any type of treatment until we get the options all sorted out. So my thought would be to get him on these drugs to keep the cancer from aggressively growing.

I'm getting my father in for a second opinion at City of Hope, Duarte CA.

Are there any members out there who's in the same situation as my father? What's your experience like? Would love to hear it.

Hi Tom,

Hi Tom,

It sounds like getting a 2nd opinion at City of Hope is a good idea. I hope they are able to help create a plan that is effective at helping your dad. Unfortunately when someone doesn't respond to tarceva for more than a few months it's not very likely there will be a response to addition tarceva, though it's impossible for anyone not involved with his care to know how to read the whole story.

All best,

The second opinion apt at

The second opinion apt at City of Hope cancer left us with more treatment dilemma.

In short, my father has ruled out the 2 pathway inhibitors phase I trials. So we are left with the following options:

1. Afatinib 30mg

2. Chemo - Docetaxel (taxotere)

3. Chemo - Abraxane (paclitaxel) + Carbo Platin, or just paclitaxel alone

4. AZD9291 US Expanded Access Program (should have molecular testing for C797S mutation, which will likely cause resistance --
-------- Cedars-Sinai, where my father is being treated, hasn't gotten back to us if this is even possible to get him into the expanded program. We meet w/ him Mon 7/20 to go over options.
-------- City of Hope, not much gain, and "you wouldn't get more miles out of it, and it would take months for the approval for the access"

If you have been responding well to any of the above options. I would be grateful if you can share your personal experience.

Can a Dr please comment on #1 (Afatinib) above?


Hi Tom,
Dr West
I personally have no remote

I personally have no remote enthusiasm for single agent Gilotrif (afatinib) in the setting of acquired resistance to another EGFR TKI. There is evidence of a brief slowing of progression-free survival and no remote hint of better survival, and in fact overall survival is numerically worse in the LUX-Lung 1 trial with Gilotrif than with placebo. I think it has two main advantages that lead to it being used so commonly:

1) it exists
2) people reflexively use ANYTHING that targets EGFR in people with an EGFR mutation.

The combination of Gilotrif with Erbitux (cetuximab) has looked more promising based on results in a clinical trial that is now about 5 years old, and we haven't seen further results showing a benefit. To me, that means it's probably less impressive than we once thought. Side effects, especially rash, are a real challenge.

A third generation EGFR TKI like AZD9291 or rociletinib makes a lot of sense and is very appealing, obviously, for someone with acquired resistance and a T790M mutation. It's unfortunate that you can't get it through a trial, but one of these drugs is likely to be approved sometime in the next few months -- I hear Sept/Oct range, just as a rumor.

That leaves a 2-3 month gap, which would allow a trial of something else. Taxotere (docetaxel) is an agent with a proven survival benefit, and there's a bit of a greater benefit with addition of Cyramza (ramicirumab), which is also FDA approved with it. That may have some challenging side effects, but Taxotere is among the more active agents for NSCLC, and I hope to give it to the clear majority of my patients with advanced NSCLC at some time.

Abraxane is a fine option, quite tolerable, but it's weekly and not a hint it's better than Taxotere, with or without Cyramza. There's not even evidence it's as good as Taxotere. So I think a Taxotere +/- Cyramza approach might be a fine option while waiting for FDA approval of AZD9291 or rociletinib.

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

Dr West, thank you very much

Dr West, thank you very much for your comments. I really appreciate it.

We're still in treatment dilemma. We are seeing the orig Onc at Cedars-Sinai to finalize a treatment option.

After much reading, I agree that Afatinib may not be as effective as chemotherapy at this time.

There have been a lot of overwhelming information; however, thinking positively...being overwhelmed with many options can really be a good thing.

All the best!


Hello Dr. West,

Hello Dr. West,

I think TOM is asking the next treatment options after failure on rociletinib (co-1868). My dad has the same situation except that he only received tarceva as 1st treatment before rociletinib (no chemo).


EGFR L718Q, L844V and C797S causes resistance to CO-1686 (Rociletinib). Only EGFR C797S leads to AZD9291 resistance. The authors have concluded that it is important to sequence for C797S mutation in patients with acquired resistance to third-generation TKIs (CO-1686 and AZD9291) to determine further treatment strategies. 

Source -

My questions:
Will you put a patient on AZD9291 if he shows progression on rociletinib? If not, is it chemo a better choice than immunotherapy for non-smoker patients? Do you know any other trials that worth a try?





I think, in general, it is a good idea to rebiopsy after a treatment that you are either not responding to or showing progression since there is a possibility the cancer has acquired another mutation, which AZD9291 (or other treatment) would be effective.

Check to see if your father's Onc can apply for a compassionate use of AZD9291. Astra Zeneca recently opened up a Expanded Access Program --

Like City of Hope, the Onc at Cedars-Sinai said that it would take 4-6 months to participate, if approved.

BTW, collectively, we have chosen to go with chemo, taxotere as a single agent for 2 cycles, then get a scan. Only then, we are able to tell if his cancer is responding, or not.


The research you've pointed

The research you've pointed to is early research not done in patients which often leads to different conclusions. If there were a choice one may choose to try one over another but given just one choice it wouldn't be an reason enough yet to deny it. We'll need more info. And there is likely no testing for it yet. But this is exciting information and the direction we hope to be moving in.
At this time there is no data to suggest one over another or whether they should be give in sequential lines of treatment. I'm sorry that there are no set answers to so many questions about nsclc care.