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April 7, 2014 at 7:30 pm #21913
Dr. Infante just delivered a talk at the AACR in San Diego on the ADC drug that I’ve been taking for 9 months, that’s very promising (phase I clinical trial). Highlights: 12 out of 19 patients got clinical benefit (if that continues, that’s well over 50%) – 4 with partial responses (meaning significant shrinkage more than about 30%) and stability over more than 6 months for an additional 8. It also works for ocular and mucosal as well as cutaneous. One woman I know with ocular has been on it for 3 years now. So while it’s no magic bullet, it’s a very effective drug. Looks like I’m one of the 4 partial responders. Here’s the link –
Personally, thanks to you folks for thinking of me so kindly and often (as on another thread – thought I’d start a new one on this, though). I’m having an “interesting” time. Clinically, the remaining tumors continue to be stable, with possibly some continuing shrinkage. I do still have issues with anemia (probably caused by slow bleeding from tumors in my upper intestines), but a recent transfusion of 3 units of red cells helped a lot. Also, I almost ended up having emergency lower small intestine surgery this past Tuesday because of a (very old – about 5 years) transient telescoping/intususseption that temporarily blocked things and caused vomiting. Just rested the gut instead on a liquid and bland diet for a few days and feel better than I’ve felt in perhaps a year (!). Got out of the hospital and went to see my grandaughter in Brooklyn on Saturday.
So, here’s my current dilemma, if you can call it that – the anti-PD1 expanded use program means I can switch over to the Merck drug (lambrolizumab or MK3475 – what are people going to call it – lambi?) in about 6 weeks, but if I go off the ADC drug from Genentech, I can’t go back (not for any clinical reason – just that it’s a trial and not available once you leave the trial). My oncologist is already beginning to suggest the switch, since he says he’s seen intestinal tumors “melt away” with anti-PD1 treatment, which would be great. He also says he thinks I’d have a better chance at a response than the reported 40% response rate. I don’t know why he said that – maybe they tested me for the PDL-1 marker without telling me the result – they did a recent paper that suggests if you’re positive for that, the response rate to anti-PD1 is a little over 50%, but if you’re negative, it’s only around 13%…interesting biomarkers coming up maybe..Here’s the link to that (I hope)..
So do I stay on the ADC as long as I’m getting the continuing stability, with some generally manageable issues (anemia, intestinal problems, plus some peripheral neuropathy) or do I take a leap for a better quality of life at maybe 50% with anti-PD1? If the side effects get worse, or the tumors start growing, there’s no question. But right now, I don ‘t know. Seeing how things go on a week by week basis. If I can get the anemia and gut issues stable so I can enjoy things more, I may stay the course. However, the travel inconvenience of flying to Nashville for treatments is also another concern. Whatever, I’m really doing well, all things considered. This has become a chronic disease for me (almost 18 years now, 7 as stage 4).
Best to all,
JonathanApril 8, 2014 at 4:04 pm #64044mmmmParticipant
Thanks so much for posting your experiences and deliberations! I understand your current dilemma, although I don’t have any suggestions. I hope you will continue to share your thoughts as they develop.April 9, 2014 at 12:43 pm #64045BNP68Participant Hey Johnathan,
Thanks for the update. As far as your question about staying the course or switching over to PD-1 I really don’t know what I’d do in your shoes. I think I’d be considering all the things you are (quality of life on ADC, travel, percentages of success on PD-1, etc…) I think the consideration of percentage of PD-1 responders is a big one. Anti-PD-1 is so often hailed as such a huge breakthrough that often we forget that for nearly half the patients it has no benefit. Before leaving the ADC trial I’d like to know the early data on some of the combo trials and when they might become available to the masses. Hopefully some of that data will be given at ASCO in a couple months. Leaving ADC for a 50/50 PD-1 is a tough call but leaving ADC for a combo that’s showing upwards of 70% response rates is a little easier jump of faith.
Take care and glad you are getting a chance to enjoy the grandkids.
BrianApril 9, 2014 at 2:27 pm #64046PatWParticipant
Johnathan, as you yourself said, knowing whether your melanoma is PD1+ or not is an important factor in this decision. I suggest that you find out if your PD1 status has been determined. If not, can you request that it be done? And how about PDL-1 (which is getting a lot of good buzz). Do different people express PDL-1 differently? Is there a test for that?April 9, 2014 at 4:54 pm #64047rochelleParticipant Greetings,
Jonathan…good to hear from you, though I am sorry to hear about the emergency surgery…I hope you’re feeling back to your old self…and what a dilemma having to make a choice in regards to treatment..I think there may be many of us on MIF faced with making a similar decision. I have been having this discussion with MSK and NYU and for right now, I am going to ride out PDL as long as I have some kind of response. Pat W mentioned testing for PDL expression and when I began the PDL trial, I asked the question…”does MedImmune test for the expression of the PDL ligand” and the answer is no. Not now and the immunotherapy team doubts the drug companies will get that sophisticated because even if a tumor does not express the ligand there is still the possibility a person with melanoma may respond. The percentage of response is lower but still viable. All in all..I’m just happy to be having to make a choice about anti pd 1 when just six skinny months ago…I didn’t have a choice at all
What I’m hoping for is to get myself on one of those combo trials!! I’m ready!!
All the best to everyone!
MarthaApril 10, 2014 at 2:58 pm #64048Catherine PooleKeymaster
Good to hear from you too Martha. I know it is a predicament and I agree that PD1 has been hyped a lot in the press (investment driven?) and it is tough to know what to do in these circumstances. I hope the ADC racks up some more patients/trials so we know more there too.April 10, 2014 at 5:37 pm #64049FrancoiseParticipant For those of you interested, the entire audio and slides for this presentation are already online on the AACR website, under “AACR Webcasts”. I even figured out where Jonathan’s data is on the slides! He is doing pretty well!
Other presentations might be of interest as well. They are not all posted yet, some will never be, and some will only be posted for members or at a cost.
FrançoiseApril 10, 2014 at 10:42 pm #64050Celeste MorrisParticipant
Just have to steal the moment and say it: You’re awesome!!!!
Love, cApril 11, 2014 at 12:09 am #64051
Well, Celeste, I have to agree about Francoise!
Thanks to you all for the clear (and supportive) thinking. Martha, you’ll have to tell more details about your anti-PDL-1 experience, since that’s a new and promising wrinkle.
After looking at Infante’s paper (still a tiny sample), one possible conclusion is that, even though it’s not been running at full tilt over a long time, it looks as though there aren’t a lot of people who can (or do) continue on it for a year or more, so at 9 months, I’m already one of the ancient vets (of course, there’s the ocular lady who’s been on it at an extremely low dosage for 2 years now, and continuing in good health). So this MAY be a reason they have been slow (in my estimation) to expand it beyond Sarah Cannon, the Angeles Clinic, and the Aussie locales. Waiting to see how we vets do before investing $$$ in a phase II trial…When I went on this last June, the clear expectation was that it would expand relatively quickly to the northeast and other centers, which hasn’t happened (therefore lots of traveling).
I’ll be getting a new set of scans on Tuesday, but I do anticipate, if the tumors are stable, Infante will suggest continuing at a lower dosage, which I will readily accept. The slides in the presentation also don’t show any relationship between dosage and response, anyway, and I’d love to see if a lower dose would help with the anemia and neuropathy.
BTW, what does look pretty clear in the talk is that people with a high expression of the tumor target (from biopsies, archived and fresh where available) really are far more likely to get a good and continuing response than those who don’t (I’ve got high target expression), so this may end up being a very good biomarker in the future.
All the best,
JonathanApril 17, 2014 at 11:38 pm #64052jamesaParticipant
I have been praying that your scans show good results from your treatments.
Hang in there, my friend.
JamesApril 18, 2014 at 11:50 am #64053Catherine PooleKeymaster
Jonathan and Francoise,
You two are such troopers, all that you’ve endured! Francoise, you are the ultimate researcher and support person. Jonathan, you still have a sense of humor. I hope you find the next decision easier on therapy. But as we all know none of this is easy. Keep in touch! Bettina and I will be at ASCO together, finding some answers we hope as we soak up the science!April 18, 2014 at 7:05 pm #64054FrancoiseParticipant
Thank you all for your strong support (and the compliments). Jonathan’s scans this past week were not quite as good as we had hoped, but still better than a year ago. The decision of switching from the ADC drug to anti-PD1 is now clearer.
But we both would like to acknowledge that the ADC drug bought us a lot of time (a year), and it would not have been possible without your suggestion Catherine. We are very greateful to you, and also glad that you are leading us towards the EAP for anti-PD1. You are a great benefit to the melanoma community. When I was a cancer patient myself (29 years ago, Hodgkins’ lymphoma), this kind of forum unfortunately was not available.
FrançoiseApril 18, 2014 at 11:58 pm #64055jamesaParticipant
I am sorry to hear that Jonathan’s scans were a little disappointing. However, I believe that everything happens for a reason. Now, you have more clarity toward moving forward with EAP Pd1.
EAP PD1 can perhaps turn into Jonathan’s miracle drug. Merck’s PD1 can give you new hope that Jonathan can be NED once again.
Please give my best to Jonathan and keep us updated.
I am praying for you both,
JamesApril 28, 2014 at 10:21 pm #64056
James asked me to recap and summarize my experience with the experimental ADC drug, DEDN6526A (thanks for all the positive vibes, James). As I read over this thread, I think most of the critical detail is already there, so rather than begin a new thread, I will just add a few points for completion and emphasis.
1. This is a very promising form of chemotherapy that, still in early trial, looks to have well over a 50% response rate/benefit for advanced melanoma patients of all sorts, including ocular melanoma. Responses can be clear within a couple of weeks.
2. Responses generally involve some, or a little, tumor reduction (rarely more than 30%), followed by stability for some time. The longest response thus far is a person who continues in relatively good health for over 2 years now – she never got tumor reduction, but achieved stability early on. However, for whatever reasons, most responders have not continued on the drug for a full year.
3. The responders generally have relatively mild side-effects for a chemotherapy – most commonly fatigue (especially following infusions), diarrhea, peripheral neuropathy, etc. but they’re still there to deal with, and have caused some to drop out.
4. There seems to be no relationship between drug dosage and response rate or response character. In fact, the most long-lasting response was achieved with a very low dosage.
5. It looks very much like responders will be easily identified with biopsies of their tumors that will show high levels of the target antigen for the drug. There is no apparent relationship between responders to this drug and BRAF, IPI, or other earlier treatment status – an entirely different mechanism at work.
6. Conclusion – this is going to be a good treatment choice for a variety of patients, especially those who have failed a variety of earlier treatments, or who have ocular or mucosal melanoma. It offers a relatively rapid response. However, for most, it is not going to be durable beyond a year.
Personally, this drug has bought me almost a year of decent quality life, and may well serve as a bridge to a better and more durable treatment (i.e., anti-PD1). I achieved a 30% reduction in tumor volume within the first 6 weeks of treatment, followed by stability for some months, and then a slow but clear resumption of tumor growth more recently (no new tumors though). At this point, almost 10 months since I began, my measurable tumors are approaching their initial levels. More importantly, my clinical symptoms are getting worrisome because of a most likely tumor related blockage in my lower small intestine and also anemia (probably related to tumors in my upper small intestine). These effects landed me in the hospital 3 times this month and almost ended up with surgery, but the surgeons are reluctant to undertake, since they aren’t sure what they’ll find when they open me up. However, I’m home now on a clear liquid diet (broth, Jello, tea, hard candy), going for walks etc and not too weakened (lost about 10 pounds in the past month). I may graduate to a full liquid diet tomorrow (yoghurt, pudding, cream of wheat, ice cream, etc). So I’m anxiously awaiting a seat in the anti-PD1 EAP, which should be opening soon at my oncologist’s clinic at Yale (mid-May, just around the corner).
Best regards to all,
JonathanJune 3, 2014 at 3:17 am #64057lindamgParticipant
I thought I’d add a bit to this chain as my husband Steve has been on this trial (ADC) at Sarah Cannon since January, and it looks as if we will be moving on to another drug as well.
His scan 6 weeks ago was characterized as “90% good”, with some shrinkage and some new growth in others. We waited to see if perhaps this would stabilize, but the scan this week showed more growth in some, new tumors on his spleen, although some reduction in one or two other locations. Overall there was more growth than shrinkage.
Over the course of being on the trial Steve had several small mets shrink and disappear, the mets in his lungs improved, and he no longer has any subcutaneous mets. He is still in better shape with his tumor burden than in January. He moved into this trial after progressing on ipi. The ipi did appear to kick in late and there’s no way of knowing how much of the change is attributed to each.
Overall, this trial did what we expected. It helped, it was never expected to eradicate the cancer and it bought time to wait on other treatment. With prior ipi use and being BRAF negative this was the best option at the time. I’m very glad this trial was available.
The worst side effect for Steve has been the progression of peripheral neuropathy in his hands and feet. His last infusion on Thursday was at a lower dose, and the neuropathy still progressed. The partial numbness has extended past his fingers and is now in his hands. It’s all still tolerable but with the latest scans it seems a good time to move on.
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