While many patients attain a response to immunotherapy (about 40% to either anti-PD1 product and about 60% to the ipi/nivo combo) and many of THOSE responses are durable, it is clear that way too many patients are left with an inadequate response or progression after those therapies. So, then what? Here is a recent post containing reports on how to address that scenario: How to deal with recurrence on or after anti-PD-1 as adjuvant or treatment for active melanoma disease
Now, there's this ~
Outcomes after progression of disease with anti-PD-1/PD-L1 therapy for patients with advanced melanoma. Patrinely, Baker, Davis, et al. Cancer. 2020 August. 1.
Greater than one-half of patients with melanoma who are treated with antibodies blocking programmed cell death protein 1 receptor (anti-PD-1) experience disease progression. The objective of the current study was to identify prognostic factors and outcomes in patients with metastatic melanoma that progressed while they were receiving anti-PD-1 therapy. The authors evaluated 383 consecutively treated patients who received anti-PD-1 for advanced melanoma between 2009 and 2019. Patient and disease characteristics at baseline and at the time of progression, subsequent therapies, objective response rate (ORR), overall survival, and progression-free survival were assessed.
Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%).
Of 383 patients, 247 experienced disease progression. The median survival after progression was 6.8 months. There was no difference in survival noted after disease progression based on primary tumor subtype, receipt of prior therapy, or therapy type. However, significantly improved survival after disease progression correlated with clinical features at the time of progression, including normal lactate dehydrogenase, more favorable metastatic stage (American Joint Committee on Cancer eighth edition stage IV M1a vs M1b, M1c, or M1d), mutation status (NRAS or treatment-naive BRAF V600 vs BRAF/NRAS wild-type or treatment-experienced BRAF-mutant), decreasing tumor bulk, and progression at solely existing lesions. After progression, approximately 54.3% of patients received additional systemic therapy. A total of 41 patients received BRAF/MEK inhibition (ORR of 58.6%, including 70.4% for BRAF/MEK-naive patients), 30 patients received ipilimumab (ORR of 0%), and 11 patients received ipilimumab plus nivolumab (ORR of 27.3%).
The current study identified prognostic factors in advanced melanoma for patients who experienced disease progression while receiving anti-PD-1, including lactate dehydrogenase, stage of disease, site of disease progression, tumor size, and mutation status.
There is also this:
Patterns of failure after immunotherapy with checkpoint inhibitors predict durable progression-free survival after local therapy for metastatic melanoma. Klemen, Wang, Feingold, et al. J Immunother Cancer. Jul 2020.
Background: Checkpoint inhibitors (CPI) have revolutionized the treatment of metastatic melanoma, but most patients treated with CPI eventually develop progressive disease. Local therapy including surgery, ablation or stereotactic body radiotherapy (SBRT) may be useful to manage limited progression, but criteria for patient selection have not been established. Previous work has suggested progression-free survival (PFS) after local therapy is associated with patterns of immunotherapy failure, but this has not been studied in patients treated with CPI.
Methods: We analyzed clinical data from patients with metastatic melanoma who were treated with antibodies against CTLA-4, PD-1 or PD-L1, either as single-agent or combination therapy, and identified those who had disease progression in 1 to 3 sites managed with local therapy. Patterns of CPI failure were designated by independent radiological review as growth of established metastases or appearance of new metastases. Local therapy for diagnosis, palliation or CNS metastases was excluded.
Results: Four hundred twenty-eight patients with metastatic melanoma received treatment with CPI from 2007 to 2018. Seventy-seven have ongoing complete responses while 69 died within 6 months of starting CPI; of the remaining 282 patients, 52 (18%) were treated with local therapy meeting our inclusion criteria. Local therapy to achieve no evidence of disease (NED) was associated with three-year progression-free survival (PFS) of 31% and five-year disease-specific survival (DSS) of 60%. Stratified by patterns of failure, patients with progression in established tumors had three-year PFS of 70%, while those with new metastases had three-year PFS of 6%. Five-year DSS after local therapy was 93% versus 31%, respectively.
Conclusions: Local therapy for oligoprogression after CPI can result in durable PFS in selected patients. We observed that patterns of failure seen during or after CPI treatment are strongly associated with PFS after local therapy, and may represent a useful criterion for patient selection. This experience suggests there may be an increased role for local therapy in patients being treated with immunotherapy.
Melanoma sucks great big green hairy stinky wizard balls! Hang tough, peeps. Hang tough! - c
I'm getting so confused. My double drug treatment is on hold for irAE to calm down, and steroid use is reduced. I was very optimistic, and thought result were far better than this. Now I'm feeling a dread sneak into my consciousness. Many times I don't understand the lingo, and I'm not stupid. Thank you for all of the time you put into this blog. I always try to check it out.
ReplyDeleteIf you mean that you are on the ipi/nivo combo, yes - a roughly 60% response rate is what the data has proven to be. As sucky as that is - it means that more than half of folks respond and that is ever so far from where I started this journey with only interferon - a drug that makes you extremely ill and has absolutely no clinically significant effect - as a treatment option. I long every day for the availability of melanoma treatments that are far more effective with even fewer side effects than your current treatment. But, do take heart. I am still here post brain and lung mets after a clinical trial of low dose nivo as the only effective agent with its 40% response rate when used as a single agent!! Further, the articles posted here give options (that do work) for patients who end up progressing after treatment on current immunotherapy. I am sorry you are dealing with side effects. However, we know that drug holidays and steroids used to deal with side effects do NOT diminish the response to these drugs. Here is a link to a post, with lots of links within it that address that fact: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2018/02/for-jubesand-rest-of-us-anti-rheumatic.html
ReplyDeleteFurther, we know that many folks cannot tolerate all the recommended doses of the ipi/nivo combo. But - there is this very heartening report: https://chaoticallypreciselifeloveandmelanoma.blogspot.com/2017/08/40-of-melanoma-patients-stop-ipinivo.html
I know it can all be very depressing and confusing. Most of my posts have my own take written below them in red that hopefully makes them a bit more comprehensible. Hang in there. Melanoma sucks great big green stinky hairy wizard balls, but there is a great deal of reason for hope.
I wish you my best. les
My doctor is very optimistic about my prognosis. I have had a huge response in now showing no visible tumors with stage IV metastatic melanoma. Had spread to liver and brain, and was 6 to 8 weeks from death when I discovered this! So, yes, there is reason to remain hopeful. I went from total exhaustion, to being able to go back to barn work (horses are my thing). I have enjoyed most of my summer. Been going outside at 3 am just to look at the sky. Steroids did make me manic, and I manic shopped online and now am the proud owner of a Breville super duper Air fryer thingy, among many other thingys. I have had fun. So I am grateful for the miracle of life and this treatment. And for people like you who share such valuable time and information and care. You are a huge lifeline to connect with, personalizing info like this, making it palatable. Lucky to have found you.
ReplyDeleteSo glad you are demonstrating such a response!! I too have spent many enjoyable hours in a barn with a mulish pony named Cupid that belonged to my children and his stable mates. Thanks for your kind words. May your response and joy in the barn, your air fryer, the beauty of the nights sky, and whatever else strikes your fancy - long continue. c
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