Home Forums Melanoma Diagnosis: Stage IV Advice about treatment

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  • #22129
    Ninni
    Participant

    Hi all!

    I have written before and now I have a new question.

    In the beginning of this year I had 6 doses of PD1 (I was in the study nivo/dacarbazine). I finally got to know I had got nivo.The scan after 9 weeks showed no result or a little progression (some mm) of the tumour. We didn’t know then that I was getting nivo, can nivo have a delayed effect and work first after 9 weeks I mean should it be worthwile to continue the trial? Instead I was quitting the study and put on ipi. I had my only yervoy infusion April 30. Poor liverfunction forced me to stop yervoy. I got cortison and am still on it but am scaling down now to 10 mg. My liverfunctions are now normal but my oncologist told me that perhaps I must always be on cortison.

    My oncologist mean that it’s too risky to have any type of immunotherapy after this but I wil argue for Mercs PD1 EAP. What do you with your experiences recommend as next treatment. I read in a thread that one patient had cortisone at the same time as getting PD1, is that doable? In another thread Catherine wrote that PD1 can work long time after the infusion. A couple of weeks ago my surgeon looked into my sinus and he thought that the tumour hasn’t grown since just before christmas when he last looked at it, rather had shrinked a little.

    Are there the same results and side-effects with Mercs PD1 as from nivo? I had CT yesterday and am seeing my oncologist tomorrow so I really would appreciate som good advices before that. I think my oncologist wil argue for dacarbazine which has helped another of her patients in a situation like mine.

    Ninni

    #65153
    Celeste Morris
    Participant

    Hi Ninni,

    Sorry you are having such a time. It is well documented in many studies that positive reactions to all immunotherapies (ipi and anti-PD1) can be delayed.

    Additionally, though you can find small differences in various studies, Merck’s anti-PD1 product (Pembrolizumab) and BMS’ anti-PD1 product (Nivolumab, now Opdivo) are pretty much neck and neck in response rates (Ribas and Weber have discussed this in particular, and several reports out of ASCO this year echoed this) and are very similar in their side effect profile.

    Perhaps more important for your situation, the fairly recent development of allowing folks who had to stop ipi due to significant side effects to take anti-PD1 has taught us that those patients are NOT necessarily destined to repeat those difficult side effects. Report from ASCO 2014:

    Updated survival, toxicity, and biomarker of nivolumab with/without peptide vaccine in patients naive to, or progressed on, ipilimumab

    Abstract 3009, J Clin Oncol

    Weber, Kudchadkar, Gibney, et al.

    105 patients with unresectable melanoma, who had failed at least one regimen were enrolled and given nivo at 1, 3, or 10mg/kg. 34 patients were ipi naive. 10 patients had failed ipi with grade 2 or less adverse events. 20 patients had filed ipi with grade 3/4 adverse events. All of these patients were HLA A0201 positive and were given peptide vaccines along with nivo. 41 patients had grade 2 or less ipi reactions and were not HLA restricted and were given nivo alone. Median f/u was 15 months. Median progression free survival was 4.2 months. Median overall survival was 16.7 months, with a one year survival of 65%. Median overall survival was similar for ipi naive or ipi refractory. Of 20 patients with grade 3/4 ipi reactions, only one had a subsequent grade 3/4 nivo reaction and it was different from the one experienced on ipi. Conclusion: Median overall survival of 16.7 months with nivo was observed in previously treated melanoma patients naive to or failing ipi. Prior adverse effects to ipi were not replicated with nivo.

    My take: So…you can fail ipi and/or have a bad reaction to it and you may still respond to nivo and are NOT doomed to experience a repeat of your adverse reaction. Median overall survival for MK-3475 and Nivo are looking pretty similar.

    Wishing you my best. Celeste

    #65154
    Ninni
    Participant

    Thanks a lot for your quick answer Celeste! Thats what I wanted to hear. Now I hope it’s possble for me to get Mercs EAP.

    Ninni

    #65155
    Catherine Poole
    Keymaster

    At ASCO this year, it was stated that the Merck PD1 had a higher response rate than the BMS Nivo. Combining IPI and the PD1 was also reported to have promising results. I am of the opinion that dacarbazine with a low response rate will not be helpful to you and does have associated toxicity. I think a longer discussion with your doctor is in order. Staying on steroids for a long time isn’t great for your immune system and why is he suggesting this? Yes, Pd1 is known to stay in the system for a long time. Where are you in treatment?

    Here is some of the data from ASCO: “the interim overall response rate for lambrolizumab was 38%, according to investigators, who reported interim data on 135 patients with advanced melanoma. The highest response rate was an impressive 52% in the arm receiving 10 mg/kg every two weeks, the highest dose in the study. Ten percent of the patients in that arm achieved a complete response, with response duration ranging from 28 days to 8 months. Four out of five patients who responded stayed on treatment. And after a median follow-up time of 11 months, the median rate of response has not yet been reached in the study.

    Bristol-Myers Squibb which has a closely watched PD-1 antibody program of its own for nivolumab reported that a third of the patients in their Phase I trial saw tumors shrink at least 30%. And they’ve seen some impressive results after combining their drug with Yervoy, another immunotherapy that relies on a different target. At a high dose, the nivolumab/Yervoy combo produced a 53% response rate, leaving Merck in a head-to-head race. Roche ($RHHBY) is pursuing a PDL-1 therapy that has also garnered the spotlight.”

    Members of our scientific board have stated that due to these numbers. first line of the Merck PD1 would be equal to the IPI/PD1 BMS combo with less side effects.

    #65156
    Celeste Morris
    Participant

    Review of data presented at ASCO 2014 RE: Nivo, Pembro and the ipi/Nivo combo:

    Nivolumab (Anti-PD1 by BMS)…provides median OS of 17 months, 1 and 2 year survival rates of 62% and 43%. ORR = 33%. AEs less significant than ipi. Immune-related events occurred in 54% of patients (skin, GI, endocrine problems), but only 5% of patients had Grade 3/4 events and there were no drug related deaths.

    …when you combine ipi and Nivo: At ASCO last year….trial data reported 4 cohorts of patients given different doses of nivo and ipi in combination. ORR across cohorts = 40% and 1 year survival was 82%. Median OS had not been reached. SAE across cohorts = 53%. Info from slide describing cohorts:

    CONCURRENT THERAPY

    induction = Nivo and ipi every 3 wks, for 4 doses (12 weeks) THEN Cohorts 1, 2, 2a, 3: Nivo every 3 wks for 4 doses then nivo and ipi every 12 weeks for 8 doses

    induction = Nivo and ipi every 3 wks, for 4 doses (12 weeks) THEN Cohort 8: Nivo 3mg/kg every 2 weeks until disease progression

    SEQUENTIAL THERAPY

    prior standard ipi therapy THEN Cohorts 6, 7: Nivo 1 or 3mg/kg every 2 wks, until disease progression

    In trial update by Sznol this year (Table below)…at optimal dose rates of 1+3 and 3+1. ORR = 43-53%. “Aggregate Clinical Activity Rate” = 81-83% in cohorts 3 and 4. (Note that Cohort 4 was the maximum tolerated dose due to SAEs and will no longer be used.) The percent of patients whose tumor burden was reduced by more than or equal to 80% at 36 weeks was 42% across the cohorts. In patients who responded the median DOR in cohorts 1-3 and cohort 8 has not yet been reached. In cohorts 2-3 the 1 year OS = 94%, 2 year OS = 88%. Median OS in cohorts 1-3 = 40 months.

    Concurrent

    Cohorts Nivo1+ ipi 3: 1 yr OS = 85%, 2 yr OS = 79%, Med OS = 40mo, Median PFS = 27 wks

    Nivo 0.3 + ipi 3: 1 yr OS = 57%, 2 yr OS = 50%, Med OS = 27 mo, Median PFS = 13 wks

    Nivo 1 + ipi 3: 1 yr OS = 94%, 2 yr OS = 88%, Med OS = NR, Median PFS = 36 wks

    Nivo 3 + ipi 1: 1 yr OS = 94%, 2 yr OS = NC, Med OS = NR, Median PFS = 58 wks

    Nivo 3 + ipi 3: 1 yr OS = 100%, 2 yr OS = NC, Med OS = NR, Median PFS = 34 wks

    These data are best-in-class for treating advanced melanoma….one outstanding issue remains that of toxicity…23% of patients had to discontinue therapy due to toxicity, and one died of complications of treatment….Sznol…pointed out that…toxicities are controlled by standard intervention…but that includes cessation of therapy. We have already learned from ipi…that responses to immune checkpoint inhibition can take time, and for those patients who have to stop treatment after 1-2 doses….time may not be kind.

    ….The activity of pembrolizumab, formerly MK-3475 (Merck’s anti-PD1) in melanoma is very similar to that of nivo…and closely resembles nivo…Slide data comparing pembro and nivo:

    Pembro, 2 & 10mg/kg every 3 wk: ipi naive – ORR = 40%, 1 yr survival = 64%, Median OS = NR

    Pembro, 2 & 10kg/kg every 3 wk: ipi-refractory- ORR = 28%, 1 yr survival = 65%, Median OS = NR

    Nivo, 3mg/kg every 2 week: ipi-naive- ORR = 41%, 1 yr survival = 62%, Median OS = 20.3mo

    Not my words guys…just published data from ASCO. Wishing you all my best, Celeste

    #65157
    Catherine Poole
    Keymaster

    But the data needs proper interpretation by an expert melanoma specialist. According to our scientific board, putting it all together, the ipi/nivo combo was in a very small number of patients, therefore does not bear out until larger numbers have been in trial. Toxicity needs to weigh in as well. The experts agreed that Pembro alone was equal to the combination numbers and far richer in data presented at ASCO. Pembro had a higher response rate than Nivo. Nothing is set in stone until we have accumulated far more data, but this is what has been interpreted so far.

    #65158
    odonoghue80
    Participant

    Hi Ninni,

    Sorry to hear that your recent treatments have not worked out as well as you hoped. It seems that you have tried Anti-PD1 and Ipi this year, and wondering what you can do next. I’m not sure if you can switch to another drug manufacture of Anti-PD1, i.e. BMS vs Merck, I don’t think you can, but it’s worth checking. I’m sure you have been tested for BRAF – have you looked into any targeted therapies like BRAF inhibitors? Let us know what your doctor says.

    Good luck,

    Shane

    #65159
    Jonathan
    Participant

    Just a brief note while getting my fifth infusion of Merck 3475. I just talked to my melanoma team at Yale about a comparison of the 2 antipd1drugs (Merck and BMS) and they say they can’t confirm any significant biological difference – the more positive results for Merck could well be because their trial population was more healthy to start with. The required head to head trial of the two drugs will probably never be done since it is in no one’s interest, including patients. As it stands, it can be argued if you fail or eventually progress after one, you should be able to argue for a course of the other, “different” drug. Hmm. Anyway, I’m happy to be on the Merck version.

    Best,

    Jonathan

    #65160
    Ninni
    Participant

    Thanks Cathrine and Shane for your answers. I saw my oncologist yesterday and had a long discussion with her (almost one hour). She appreciates that I am updated on the new treatments, mostly thanks to this forum which I check every day.

    I had a CT this monday and it showed that the melanona in my sinus had grown 1mm since april and the metastas in the lung had also grown 1 mm. My oncologist would say they were stable. But I had a new spot in the liver. Because of that she means that Nivo Pd1 had no effect on me but she would try to get me into Mercks EAP if I want that. I too am uncertain it would help but I can’t help wanting to try it. I have mucosal melanoma in my nose and sinus now inoperable but I read that PD1 is not as god with mucosal melanoma. If I get Mercks EAP and it doesn’t work I wil take my last option, dacarbazine. Somewhere I read that you can get Mercs EAP PD1 even if you have failed with Nivo, am I wrong? Mercs EAP hasn’t come to Sweden yet but is expected soon. If it takes a long time perhaps I can take dacarbazine first.. My oncologist is going to check it all up.

    Cathrine: Everytime I have tried to go under 10 mg cortisone my liver or the thyroidea reacts and I have to take a higher dose again. But I am still trying to scale down (I began with 160 mg for two weeks in hospital). I am so tired of all this and sometimes I want to give it all up but life is wonderful and I just got my second grandshild.

    Ninni

    #65161
    Cbs805
    Participant

    My husband, John has mucosal melanoma of the sinus and is now on the Merck PD1 expanded access program. He had his first scan a few weeks ago at 5th dose and there were no new tumors and many had shrunk. Some had gotten bigger but the doctor wasn’t concerned as that sometimes happens as the drug can be loading the tumors with T-cells I think. Next scan is in 2 weeks and Dr. O’Day (Beverly Hills Cancer Center) seems to expect further good results. Currently, besides fatigue and itching, he was experiencing trigeminal neuralgia as a result of surgeries and/or radiation. Thankfully, he is on medicine that has alleviated that problem. His original diagnosis was April, 2013 and became stage 4 in December. Has had IPI twice, and completed 6 doses of PD1 so far. Previous treatment included surgeries, chemo, radiation, CyberKnife, etc. We have never asked about PD1 results of melanoma versus mucosal melanoma. We do know another mucosal patient who is having success with PD1 though.

    #65162
    Catherine Poole
    Keymaster

    Yes, I do believe success is being found for some cases of mucosal with the PD1. Ninni, I would give the Merck PD1 a shot and see if you have better success than the NIVO. And yes, you can have prior PD1 therapy to get into the Merck EAP, (but not vice-versa, NIVO eap doesn’t allow prior PD1) It sounds like you have a great doctor working with you and I hope this will help you. I would also do some research to see if there are any clinical trials for a plan B, rather than dacarbazine as the next plan.

    #65163
    mary1233
    Participant

    My oncologist at sloan is part of the clinical trial doing the ipi-nivo combination. I will see him the beginning of September (hopefully my scans will be clear). So much has changed since I was diagnosed in 2012.

    #65164
    Ninni
    Participant

    Thanks Jonathan for your informative input. I have read your previous posts and really hope that Mercks PD1 wil work for you!

    And thanks Cbs805, your comment was encouraging and thanks Mary, I hope the nivi-ipi-combination wil work for you.

    Thanks again Cathrine, I now hope I wil get Merck EAP. I always look for a plan B. Helledays trial can perhaps start next year http://www.helleday.org” class=”bbcode_url”>http://www.helleday.org

    ninni

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