This may not be what you are after, but Jazz posted a bit about the trial here:
Thanks for this post. It sounds like the "side effects" was mainly due to Tarceva rash in the first place. Believe me, I am very familiar with that. Again, she had the "pneumonitis" which may be due to the lung cancer.
Craig, Re: DS-2248 - I looked for data too and found nothing notable, which is why I'll have to pick Dr. Camidge's brain about it. I couldn't probe Dr. Ou too much, as my father was the patient he was seeing that day.
Blue Skies, How the heck are you? What's up? Hope you are well.
Ssflxl, Thanks for the MK-3475 info. This trial is also at UCLA and Angeles Clinic in SoCal. I'm trying to figure out how people get randomized to the low, medium, or high dose for the NSCLC arms. FeistyD had a 70% tumor reduction at her 12 week scan but we've not heard since so I'd be curious to know.
As for the MK-2206 trial at Davis - The first month I was on it I felt marked improvement. Side effects consisted mainly of a cough I couldn't shake, extreme photosensitivity, postnasal drip. There was a bit of a rash, but after a day in the sun the rash was out of control! (This is definitely true of Afatinib, for me anyway). I think the max dose was working, but once I had the dose reduction, I don't think disease control was very robust. I thought my wheezing was pneumonitis related, but when I went off MK2206 and returned to Tarceva 150 alone, the wheeziness resolved. Dr. Camidge doesn't believe Merck will continue development of this drug in NSCLC, or at least that's what I thought he said when he found out I was on it prior to Afatinib. On the other hand, it stabilized me from June to November, so it can't be all bad. I got some functionality back, and I'm much more heavily pretreated than you, so you might have some success. I believe the conclusion was that I had an "unconfirmed partial response". Visits are very perfunctory, btw, not warm and fuzzy. Just so you know.
CS, Wow! Thanks for the Link-o-rama! What a discussion of the BBB! I'm sorry I didn't make Rob's acquaintance, especially as we both lived in the SF Bay Area. I'll report back if I find any more info.
Jazz, since you are so knowledgeable, and are unusual in having experienced a) afatinib on its own; and b) afatinib and cetuximab together (if I've got that right), could you give us your overall impressions?
In particular, have I got the right idea in thinking that the really tough side-effects come from the afatinib? And did it make much of a difference when they added the cetuximab (to the side-effects, and to your well-being/response?)
I've posted on FeistyD's thread, hopefully she will respond.
She did respond, here's the link, she's doing well, still responding and is due next week for another scan. http://cancergrace.org/topic/anti-pd-1-immunotherapy-clinical-trial-update
CS, re: afatinib/cetuximab impressions - I was not in the sequential arm, although I was originally slated to be. I arrived at my first infusion and heard, "surprise! You're getting both agents today!" The other person starting that day was disgruntled and later had a severe reaction to cetuximab, on top of the snowstorm which cancelled our flights! So I'm mostly familiar with the combo experience except during the short tx break I took in July. I skipped one infusion due to side effects, but decided to restart afatinib because it seemed i was coughing more. During the two weeks on afatinib only, I developed rash in other parts of my body not previously affected. Furthermore, the rash had different characteristics than the combination rash, which was odd but true.
Cetuximab confers its own side effects, which are very similar to afatinib (rash and diarrhea - my experience is that cetuximab causes diarrhea right after infusion, and afatinib just keeps it going!). Some people do not experience the scalp rash until they take cetuximab. Others have it on afatinib alone. I believe the paronychia is primarily an afatinib side effect, as are the hand and feet fissures There was a UK poster on Jing's thread, I believe, who'd been on afatinib single agent for almost two years. It was her first line tx. Will have to search.
In conclusion, I'd say afatinib is much tougher to tolerate than Tarceva, and that I truly believe cetuximab doesn't necessarily add too much more in terms of side effects, but I seem to feel slightly better after infusion.
I hope this helps a bit. Either way it's worth overcoming acquired resistance to Tarceva!
Thank you, Jazz. Sometimes our discussions get so detailed that it's hard to see the wood for the trees, so it's very helpful to have an overview.
Afatinib (alone) is the likely post-Tarceva option for me when the time comes (here in Britain, as things stand). I am not confident I could cope with the side-effects as I am a mega-wuss.
I think this is the lady who posted about first-line afatinib - her name is Debbie:
She is active on a UK cancer website, helping and supporting others - I am pretty sure it is the same person.
Brief update here. I'm now on the 12th cycle of the trial. HOWEVER, things are growing. My scan of 12/12/12 revealed "slight increases" in two of the target GGO's, and possibly even the target lymph node. I'm allowed to stay on the study beyond progression - how much progression wasn't really clear. Maybe clinically significant progression, or 30% beyond baseline? I'll get clarification at some point. No one seem very alarmed, although I suspect this is a cultivated behavior! There was more of a, "ride it out until we find the MTD for CO-1686" thing. Needless to say, I'm looking very keenly for options.
Re: CO-1686 - problem seems to be with its short half-life, so they're now working on revising dosing schedules, as very high doses have been reached but it's in and out of one's body much too quickly. No side effects still, so that's good. I really hope thy figure this out SOON.
DS-2248 (HSP90 inhibitor) - didn't find out too much more about this, although Dr. C is skeptical of reaching high enough blood concentrations to achieve efficacy in EGFR mutants. With the exception of AUY922 (which had severe ocular toxicities), other HSP90 inhibitors were effective mostly on ALK and K-ras histologies. (Disappointing results from the ARQ197 (Tivantinib) phase 3 trial, if anyone recalls that far back.)
MK-3475 - probably a better choice than the above agent (for me, anyway). The BMS anti-PD1 drug had some adverse events ... not much info out on this one. If randomized to the agent + chemo arm, it's probably treater's choice. I'll call to get more info next week, methinks.
Any other promising morsels anyone else knows of, toss them out!
Thanks and best to all,
Terrific info, Jazz. I'm sorry to hear of the slow growth, but having many patients in your situation, I think there's good reason to not panic when the progression is indeed slight. And we know Dr. C is as knowledgeable as they come as you work with him to devise the next steps of your treatment plan.
Dr. Howard (Jack) West
Associate Clinical Professor
City of Hope Cancer Center
Founder & President
Global Resource for Advancing
Best of luck to you. Try to rest up for the holidays. Are you still in SCAL?
Thanks for the reassurance, Dr. West.
Ssflxl, yes, still in SoCal and will probably be here for the long run (unless we move to... New York?). Am having trouble with Kaiser. Be vigilant with the billing if/when you go on an outside clinical trial. I'm paying a very high premium for converting my group plan after COBRA. Now I can't buy Medigap insurance, and Kaiser insists Medicare is my primary insurance. So be careful with that. I'm only breaking even because they've been paying for my flights to Denver. I plan to switch from NorCal KP to SoCal KP once my stint in Denver is over. Anyway, I hope you're enjoying the season and feeling well.
Let's hope the vaccine results will come out favorable early next year and ultimately gets FDA approved. That would give us another option!!
Just posting some info I discovered from inquiring into the CO-1686 trial at UCLA. The current dose cohorts (still in dose-escalation phase) are 1200mg once, twice, and three times a day (3 patients per dosing schedule). There are currently 9 people on their waiting list (I'm #9), with new cohorts opening roughly every two months. As you can imagine, I can't wait that long! I don't know what the list looks like at UC Denver but will inquire on the 9th. This trial requires a fresh biopsy so I'd still need to get around that. (And I don't intend to fly to Michigan or NY, even if they have space. I'm tired of flying!)
MK-3475: This trial is scheduled to open at the end of this month or early February. I'm #2 on the waiting list. I qualify for Cohort F (single agent, randomized dose - low or high), pending tumor expression of PDL-1. The other NSCLC cohort (E) is combined with chemo, and is first or second-line restricted. Wash-out period is a month.
That's the news for now!
Is the MK3475 trial in UCSF? When I inquired, they said they are not open yet.
Good luck Jazzy Jazz. . .I've got everything crossed for you (fingers, toes, legs, arms, hairs. . .etc...) so that you can get into the UCLA trial. . .
Thanks, Laya. I echo Gail's sentiment - I salute you and am humbled by your kindness and fighting spirit while enduring excruciating emotional pain. You are Bilbo Baggins defending the dwarf king against the pale ork! I was just making peace with possibly dying this year, but with you and fellow GRACERS by my side, I may yet live to see another day. I am ever so grateful for your and the many great examples of advocates on GRACE, as I also try to navigate the waters with my Dad.
Ssflxl, I imagine UCSF's MK-3475 study mightt open around the same time as UCLA but you'd have to ask specifically. It is already open at Angeles Clinic, where FeistyD goes, but I don't know where else.
Jazz & Ssflxl,
MK-3475 locations are listed in the trial's details here, but they are ambiguous about showing more than the town:
You can probably call for more details.
Stage 4 ROS1+ [mucinous BAC] adenocarcinoma NSCLC since 2011
Xalkori (crizotinib) 5 yrs
Alimta (pemetrexed) + carboplatin (mere months)
TPX-0005 (repotrectinib) TBD (1+ years as of Fall 2018)
Just got word - the MK-3475 trial opens on Jan 30th at UCLA. Can't recall if I posted this in Community Updates or not. It's Phase I, with Arms E and F for NSCLC.
First I want to remember two heroes of this thread - Jing (FaithandHope79) and Ann (Blue Skies). They brought such spirit and wisdom to GRACE, and hold their place among the many heroes who have blessed this site and our lives.
On the update front - I finished out 13 cycles on Afatinib-Cetuximab at U of CO. My 1/29 PET scan showed progression and new mets in the bone (T12, and uptake in L1, L5), on the adrenal gland, and activity in my collapsed left lung, which is impossible to image, among other hypermetabolic areas (vocal chords, closing off of bronchial tubes to the left lung). I can't bring myself to read the report in its entirety, due to the severity and the 4-page length! I was roughly in this state at this time last year, progressing rapidly, feeling debilitated - except I had two lungs then, no new mets, and this trial. This scan led my home oncologist to prescribe morphine for pain and hand me a POLST form with a recommendation to discuss end-of-life issues. It made my husband realize I wasn't just being dramatic when I paused, gasping for air, at the top of the stairway.
Dr. Camidge (Denver) was less alarming and conveyed the situation as not as bad as it sounded. The upside of the adrenal gland met was now I had a biopsy site other than my only remaining lung. This is helpful for the trials I want to enroll in - CO-1686 or MK-3475, both of which need fresh tissue for testing. Unfortunately, the Clovis trial has not reached MTD, and the Merck trial requires a 4-week washout period. The current rate of my progression necessitates stabilization ASAP, so I'm to start Carbo-Gemcitabine-Tarceva this week. If not tolerable, I'll drop the carbo, so gemcitabine-Tarceva combo, 4 cycles. Hopefully the Clovis trial will be ready in a few months, or I'll be stable enough to attempt the PD-1 trial. In any case I plan to do a consult at UCLA soon.
It's a relief to break from traveling, but am nervous about the future.
Completely endorse your words about Ann and Jing. Two wonderfully kind and practical women. I learnt a lot from their matter-of-fact approach to the disease. I am glad they got to know each other.
Poor Jazz, the breathlessness sounds grim. You have to take everything slower - it is frustrating but it is the only way. And don't carry anything. Not even a small bag. It makes things worse.
Hold your nerve xxx
Hi Jazz, thanks for updating and sharing of your experience. Our thought are with you. One good thing is that you have the care of Dr, Camidge who Dr. West has endorsed as one of the most knowledgeable in the field and he seems to have confidence in helping you to deal with it. Take care ang good luck.
I'm so sorry to hear about your progression, Jazz. But yes, Dr. Camidge is a friend and a very thoughtful, extremely knowledgeable colleague who is among my very favorite people in the field, and I very much like most of my colleagues. I would absolutely entrust him with the care of a member of my own family in a heartbeat.
I am sorry to hear about your PET. It doesn't appear you have tried Taxotere yet, so have you discussed that with your onc? Maybe Abraxane which is better tolerated? Just an idea!!
Jazz - I'll be interested in how you fare on your return to carboplatin. My onc has also mentioned returning to a doublet. I had 10 carbo infusions in 2007-2008. I wasn't real high on the idea! I hope all goes well for you. Maybe you'll inspire to give it a try if I need to go that route.
ssflxl asked about taxotere. Has it been mentioned? I restarted it yesterday (#7) after actually having a good result. I'll see how it goes.
All my best to you. You've been a great example for all of us!
Jazz, I second everything that has been said and am sending love. Hold your nerve, link arms with us, and push on. You are very much appreciated around here.
Thanks everyone for your support, and Happy Valentine's Day. Sending virtual hugs and chocolates all around!
First carbo- gemcitabine infusion down. Helluva Valentine's date! New Onc thinks I should stop Tarceva, at least until we get through the first cycle. She's worried about toxicity. While that's understandable, Dr. C didn't seem to feel that triple combo to be unreasonable. His choice would be to drop carboplatin if there were tolerance issues, and keep gemcitabine and Tarceva going. Not sure what to do, whether to try her suggestion or go with the more aggressive approach.
As for Taxotere, yes, I had 2 cycles of it back in 2006. Taxol closed my airway in under 3 minutes, and Taxotere was barely tolerated with lots of pre meds. It oozed out of my veins and burned my skin days after infusion. It was decided that I was allergic to taxanes and there is reluctance to try Abraxane. No one knows if it's the solvent or the actual compound?
More updates to come later, probably in a new thread!
Hi Jazz, I hope you are alright.
I remember the same as you that carbo would be the drug of choice to ditch if needed because of the hypersensitivity that evidently could still be an issue.
And, I think, but less sure, that you're right about the solvents being the culprit in the taxanes in the allergic reaction.
I'll contact a doctor to give some input on these questions. It's always fab to have another option on the plate.
I'm sorry to hear you've had such problems with allergic reactions. One of my colleagues at UNC actually has a strong interest in figuring out why some people are so allergy prone and I'm sure would love to get his hands on your blood if you were closer to us!
To provide some more insight, as this is an interest area of mine as well, both paclitaxel (Taxol) and docetaxel (Taxotere) are in the category of taxanes. These are big molecules that do not like to become liquid and so some less common diluents are used to make this happen. Taxol is mixed in Cremophor EL, notorious for causing allergic reactions, among other side effects (muscle aches and pains a few days after for example). If no premedications were used 40% of people would react to Taxol, though with Benadryl and steroids this drops to about 1-3% with most reactions happening within minutes of starting the infusion. Taxotere is mixed in Tween 80, less likely to cause allergic reactions than Taxol, though are still definitely possible. Tween 80 does make blood vessels "leaky" which is why we sometimes see fluid retention with the drug. Abraxane is the same paclitaxel molecule, but is mixed with Albumin instead of Cremophor (think about putting the two in a blender together to make a suspension). Allergic reactions are very very rare with Abraxane (premedications other than for nausea or not usually needed). Since you've reacted to both Taxotere and Taxol, it is possible you are allergic to the Taxane molecule, but may also just be very sensitive to substances like Tween and Cremophor.
Briefly on platinums, unlike the taxanes, platinum allergic reactions usually occur after many doses and are a different type of "allergic reaction". We often do desensitizations (giving small doses over a longer period of time) for people with platinum allergies. These are actually likely due to the drug molecule itself and not what the drug is mixed in.
Best wishes and happy to comment further if needed!
Christine M. Walko, PharmD, BCOP, FCCP
Personalized Medicine Specialist
Moffitt Cancer Center, Tampa, FL
From what Dr. Walko said, it may be worthwhile to ask your onc if you can try a small dose of Abraxane just to see if you have any reaction to it. also is it possible to desensitize against Taxotere.
There are premeds given to everyone who takes it and even extras for those like Jazz. I think she may have even been given the extra high premeds with taxotere at one point.
But I do wonder like you if her docs may give abraxane a try.
Janine is correct, I got extra premeds to get through Taxotere (docetaxel), and it was infused at a slower rate, which took forever! The backache/muscle pain was excruciating so after two cycles, my oncologist feared anaphylactic shock and switched to Gemzar. I was on a triplet at the time, which included Avastin, on a clinical trial sponsored by Genentech, So there was a high stake in getting good results, especially as I was young and fit at the time.
Thanks for the thorough explanation, Dr. Walko. My oncologist wishes we could use Abraxane, but is there a way to try a "small dose", and wouldn't that be risky? I am allergic to many grasses and trees, according to one of those allergy panel tests. Perhaps it's the Yew tree (analog). This makes me fear vinorelbine, obviously (I've also battled the invasive vine in my garden!). Additionally, I seem to be highly sensitive to all those facial creams I'm drawn to - the "organic, plant extract, no preservatives, etc" variety, especially European skin treatments (I have horror stories about facials and german creams)! Which makes me sad, except the money-saving aspect. And this may not be relevant, but something in the 21-herb recipe for gin makes me decidedly allergic to that spirit (I don't think it's the Juniper berries). But I digress.
I hope "gentle Gemzar", "the new water", works its magic as it has been on Janine's hubby!
Jazz, usually the Abraxane would just be started a slower rate to assess for allergic reactions, I dont know of any data to support a test dose like you described.
Gemzar has a pretty low risk of reactions so hope all goes well. As a note, it is not uncommon to have burning at the site of infusion with the drug. A heating pad can be helpful.
FYI, thank you for such a good explanation of the potential sensitization reactions to chemo. I don't need it any time soon, but it's worth bookmarking for future reference and sharing with others who might if it comes up again.