Hi,
I wonder whether re using afatinib may benefit my mom again. She was previously on the drug for about six months with very good results. When it stopped working, and even then the progression was quite slow, she was found positive for t790m, and started Tagrisso. However, she, from the get go, didn't seem to do well on the Tagrisso, and when we got our scan 3 months later it showed dramatic progression. We did another biopsy and sent it to foundation one and it showed no t790m, it did show the original exon 21 and several others, including the very problematic mutation, KRAS. Her mutations load was also quite high, so immunotherapy was listed as a viable option. She recently started Opdivo, 2 infusions thus far, unfortunately by the time she went into the clinic to get her third one she fell and fractured her hip, she went into surgery couple of days later. As I understand, it takes time for any immunotherapy drug to work, as of the need to get to a critical mass sufficient enough to trigger one's immune system into action. With mom's very progressive disease (she doesn't feel well at all, doesn't eat, sleeps a lot, and has right side abdominal pain, probably from the liver mets), I think it's critical to put her on a drug that works fast without having to wait too long. So my question is, would it be possible for her to take afatinib again, it would be about six months since the last time she took it, and it makes sense that some cancer cells, especially the new ones, would be sensitive to the drug. We need to stabilize her situation, to have enough spare for her to have the time to wait when trying Opdivo again. I'd greatly appreciate your thoughts, insights, or experience on re challenging afatinib.
Thank you all,
Ilan
Reply # - September 9, 2017, 06:20 PM
Hi IIan,
Hi IIan,
I'm sorry to hear about your mom's difficulty. I hope she's able to get a quick response to whatever she tries. The most likely treatment to get efficacy is a chemo platinum doublet. This is the 1st line treatment for those who have no actionable mutations. It's the treatment that has shown efficacy across the spectrum of lung cancer. Carboplatin with alimta (navalbine or gemzar if she's squamous alimta for adeno) has become a favored combination. The side effect profile of each is less than other options and the efficacy is probably as good or better. If your mom is frail and it's not thought she can withstand the platinum portion of the treatment it's fine to use alimta alone with good efficacy. This is a 4 cycle treatment. Some oncs like to go 6 cycles but data doesn't suggest you get anything more out of the more than 4 cycles and the possibility of platinum reaction grows substantially after 4 or 5 cycles. Then she can move to alimta alone or take a break which she may well need/want/earn. Many people find alimta alone to be very easy to use with no or few side effects so can be taken until progression.
Dr. West has stated he's not found that returning to tarceva to be very effective. That's one oncologist's observation but there's no trial data to support one way or other. However it's not something oncologists normally. do. Since you mom never really used up afatinib there may be occasion to try it again.
For your mom today, she needs shrinkage. Once she stabilizes looking into other less certain options might be available. It sound as if she has a few.
Keep us posted.
All best,
Janine
Reply # - September 9, 2017, 08:49 PM
Thank you Janine. Once
Thank you Janine. Once diagnosed back in Jan/16 she underwent 6 carbo/almita cycles with good results. Next she was put on maintenance treatment with almita but progressed after 2 cycles. She then went on afatinib. Once the tagrisso failed, she was put on carbo/taxol, however the side effects were very harsh so we then opted for Opdivo (I know that immunotherapy usually doesn't bode well for EGFR, however, with her other mutations, KRAS included, her mutation load is high enough which may indicate a good response). I understand that chemo is probably the safest way to go in terms of getting a good response fast, is there something else compatible with almita (efficacy, side effects), as getting back to taxol would probably be difficult for her, thank you so much for helping, Ilan, p.s. is there any sort of radiation treatment option for liver mets, they are numerous, but maybe we can target the main ones, thanks
Reply # - September 10, 2017, 11:52 AM
Btw, is there a simple way to
Btw, is there a simple way to get a read on whether Opdivo is about to work, maybe looking into some parameters of the immune system, checking through some blood tests whether the immune system is hyped enough, compared back to before of the Opdivo, thank you, Ilan
Reply # - September 10, 2017, 01:53 PM
Ihen,
Ihen,
Unfortunately the only way to tell if immunotherapy is working is scanning and clinical symptom observations. One thing to note is the pseudo progression (not progression but inflammation from immune response) you may have read about is now thought to be pretty unusual. It shows up on a scan but oncologists are finding there doesn't seem to be worsening symptoms with pseudo progression.
Carboplatin causes the same side effects as taxanes so combining them creates more toxicity. The taxanes; taxol, abraxane and taxotere are best studied to have efficacy. Gemzar and navelbine are also appropriate choices.
Abraxane is Albumin-bound Paclitaxel with fewer side effects.
Since your mom has already had 2 infusions her oncologist may be disinclined to change plans especially since she didn't respond to alimta. It is possible to respond to other chemo drugs if you didn't respond to the first but it's less likely.
Janine
Reply # - September 10, 2017, 02:30 PM
Typically local treatment isn
Typically local treatment isn't used for metastatic nsclc. It just doesn't add to longevity. There are a few situations in which local treatment is used to reduce symptoms such as bone mets or if a tumor is pushing or blocking structures. There is one other new situation in which local treatment is used and that's when a targeted therapy begins to acquire resistance. Such as with EGFR TKIs. Typically resistance begins slowly in one or two places. Local treatment to these places can allow people to continue on TKIs for much longer.
You might want to talk to your mom onc about the possibility of this being the case with your mom's progression on afatanib. Here's link to describe this, http://cancergrace.org/lung/2016/03/07/gcvl_lu_local_therapy_limited_ac…
From cancer.org the below quote is on the topic of liver cancer though could useful if thinking about treating met to liver.
"This type of radiation therapy focuses radiation delivered from outside the body on the cancer. This can sometimes be used to shrink liver tumors to relieve symptoms such as pain, but it is not used as often as other local treatments such as ablation or embolization. Although liver cancer cells are sensitive to radiation, this treatment can't be used at very high doses because normal liver tissue is also easily damaged by radiation." https://www.cancer.org/cancer/liver-cancer/treating/radiation-therapy.h…
Reply # - September 11, 2017, 11:20 AM
Thank you so much Janine for
Thank you so much Janine for helping. Mom's liver enzymes are rising very, very fast the past days. There is a possibility that this isn't all due to cancer but also gallbladder inflammation, her symptoms are dead on for that and her ultrasound of today indicates possible inflammation.Is it possible the Opdivo caused the inflammation? The reason I ask is because if there is indeed inflammation that increases liver enzymes, it's possible that the liver isn't that stressed by the cancer and we may have more time to give for Opdivo to work., thanks again, Ilan