All - I posted last week about my brother's NSCLC progression after 1st line chemo and Avastin maintenance for about 4 months. He's EGFR positive but exon 20. And today we heard that he did not qualify for a Merck PDL1 trial NCT01905657 (MK-3475-010) because his tumor was NOT PDL1 positive. MRI for brain mets clear.
He feels he is running out of time to make a decision and start treatment. It's been two months since his last Avastin treatment, he is really feeling the effects of the cancer with shortness of breath, and he doesn't want to delay by not getting started soon or picking the wrong option and then have it spread to his liver or brain. The decision is weighing heavily on him as he has 4 kids between the ages of 7 and 14. What he is struggling with is how does he make a decision / rank option when there appear to be no clear answers? Is there a way to think about this stuff so he can feel confident in whichever choice he makes? Are there other trial areas I should research for him?
If you need more detail here are the current options outlined by his doctors: Alimta, the Genentech MPDL3280A OAK trial NCT02008227, and Afatinib.
* Alimta: approved FDA treatment, but still chemo with all the side effects and cancer will progress
* OAK trial: randomized trial not requiring PDL1 expression - one arm MPDL3280A and the other Docetaxel; may not get PDL1 drug, if he gets it he may not respond; if he doesn't get the PDL1 drug he is driving two hours to get chemo that he can get locally; likely needs a new biopsy via bronchoscopy; we've been told it may take a few months on the PDL1 drug to really see if it is working; MPDL3280A seems to favor smokers and those with high PDL1 expression; then again he could be one of the great responders; or do we hope these drugs are more readily available for 3rd line
* Afatinib: his exon 20 insertion would say that Afatinib likely will not work, but it could; does he try for two months or save for 3rd line
Reply # - July 11, 2014, 07:25 AM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
I'm so sorry your brother is in the midst of this decision making.
Dr. West said this in a earlier thread, "In this case, afatinib has been shown to NOT be especially effective for rare EGFR mutations (and results of EGFR TKIs in patients with exon 20 mutations have tended to be unimpressive, or at best quite variable), and its value in treating ERBB3 (HER3) is unknown, but we couldn’t presume it will be effective. Because afatinib is not approved by the FDA for people with these mutations, it may not be covered by your insurer. Even if it’s possible to get it paid for, it very well may be ineffective." http://cancergrace.org/topic/exon-20-and-erbb3-amplification-is-afatini…
If someone is having these symptoms from the cancer it's usually good to get started with the most likely option to help get things under control and that seems to be single agent alimta. Even though he's taken it before he never progressed on it, it was 2 years ago and he is likely to respond well to it. He's likely to feel well on it without the platinum drug.
I'm sorry but there is no cure for nsclc that has recurred into the pleural space. However it can be treated with good results. There isn't enough evidence that any of the drugs penetrate the blood brain barrier but alimta may have in a few cases. To access your previous threads click on your user name "gaw1" on the left of your posts.
All best,
Janine
Reply # - July 11, 2014, 10:43 AM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
Thanks Catdander. What plays with the mind and mucks with the decision making are the stories, albeit few and far between, of people that responds to these new drugs when they don’t have the traditional markers/expressions. So you ask yourself is the risk-reward there and worth taking or is it just fool’s gold? Nature of the disease and part of the battle.
Reply # - July 11, 2014, 11:47 AM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
The thing about that is the drugs aren't proven to be beneficial and they are definitely not side effect free. Alimta on the other hand has a well proven record, with lots of data to back it up, it can last a long while, year to years even and many people have few to no side effects. Plus you may be overestimating the non chemo drugs. It's more likely he'll do well on the chemo (avastin isn't a traditional chemo and that's what he was on with progressed). But no one can say how he'll respond all we have are the data and his will to stay near home.
Another part is many many people move on to other lines of treatment after doing well on 2nd line. There are options. Have you read this? http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-o…
Janine
Reply # - July 11, 2014, 12:31 PM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
Hi Janine - I chuckle a bit as I think I have read every applicable article and thread on cancergrace at least three times if not more. If the 2nd line treatment article was in paper it would be well worn with frayed edges and tattered corners. As I can only imagine you know, when you are in the midst of making the next decision it is often difficult to see the forest through the trees. That is what I appreciate so much about cancergrace. It is such a supportive and patient sounding board for families who are struggling even when we are likely asking the same question, yet again, just using different words. Thank you all - G
Reply # - July 11, 2014, 10:52 PM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
Speaking with the evidence, I think we can only say that Alimta (pemetrexed) has the most established record. It has some potential side effects, certainly, but it tends to be well tolerated. The immunotherapy can potentially provide a long-term benefit, but's more of an unknown, particularly in those who don't have significant PD-L1 expression.
As I mentioned previously, the results with afatinib have not been especially favorable in patients with rarer EGFR mutations, and the side effect profile is a potential challenge that may well rival or exceed that of chemo.
While it's tempting to say that the trial may be a great choice because you could do the investigational treatment and then still have the options of the standard treatments available later, if you say that symptoms are getting worse, you may want to favor a treatment that has a proven record.
Good luck.
-Dr. West
Reply # - July 12, 2014, 11:26 AM
Reply To: OAK Trial, Alimta or Afatinib for second line ????
Thanks Dr. West and Janine. Your insights are valued. He has a few more doctor appointments and I believe he will come to a decision on Wednesday. Thank you for taking the time and for cancergrace.org!