Adjuvant therapy, is when a treatment is given AFTER signs of obvious disease have been removed, usually with surgery. And we have very good data that adjuvant treatments, both with targeted and immunotherapy, work in melanoma to prevent progression in many of those patients. After all, that is what the NED Stage IV ratties in my nivo trial proved from 2010 - 2013!!!!
NEO-adjuvant therapy, is when a treatment is given BEFORE melanoma has been removed.
Here are some prior posts - BRAF/MEK before surgery as well as after is MUCH better, than just AFTER surgery for melanoma!!
Now, there are these looking at immunotherapy as neoadjuvanat ~
Neoadjuvant immune checkpoint blockade in high-risk resectable melanoma. Amaria, Reddy, Tawbi, Davies, et al. Nat Med. 2018 Oct 8.
Preclinical studies suggest that treatment with neoadjuvant immune checkpoint blockade is associated with enhanced survival and antigen-specific T cell responses compared with adjuvant treatment; however, optimal regimens have not been defined. Here we report results from a randomized phase 2 study of neoadjuvant nivolumab versus combined ipilimumab with nivolumab in 23 patients with high-risk resectable melanoma ( NCT02519322 ). RECIST overall response rates (ORR), pathologic complete response rates (pCR), treatment-related adverse events (trAEs) and immune correlates of response were assessed. Treatment with combined ipilimumab and nivolumab yielded high response rates (RECIST ORR 73%, pCR 45%) but substantial toxicity (73% grade 3 trAEs), whereas treatment with nivolumab monotherapy yielded modest responses (ORR 25%, pCR 25%) and low toxicity (8% grade 3 trAEs). Immune correlates of response were identified, demonstrating higher lymphoid infiltrates in responders to both therapies and a more clonal and diverse T cell infiltrate in responders to nivolumab monotherapy. These results describe the feasibility of neoadjuvant immune checkpoint blockade in melanoma and emphasize the need for additional studies to optimize treatment regimens and to validate putative biomarkers.
Neoadjuvant versus adjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma. Blank, Rozeman, Fanchi, Sikorska, et al. Nat Med. 2018 Oct 8.
Adjuvant ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) both improve relapse-free survival of stage III melanoma patients. In stage IV disease, the combination of ipilimumab + nivolumab is superior to ipilimumab alone and also appears to be more effective than nivolumab monotherapy. Preclinical work suggests that neoadjuvant application of checkpoint inhibitors may be superior to adjuvant therapy. To address this question and to test feasibility, 20 patients with palpable stage III melanoma were 1:1 randomized to receive ipilimumab 3 mg kg and nivolumab 1 mg kg, as either four courses after surgery (adjuvant arm) or two courses before surgery and two courses postsurgery (neoadjuvant arm). Neoadjuvant therapy was feasible, with all patients undergoing surgery at the preplanned time point. However in both arms, 9/10 patients experienced one or more grade 3/4 adverse events. Pathological responses were achieved in 7/9 (78%) patients treated in the neoadjuvant arm. None of these patients have relapsed so far (median follow-up, 25.6 months). We found that neoadjuvant ipilimumab + nivolumab expand more tumor-resident T cell clones than adjuvant application. While neoadjuvant therapy appears promising, with the current regimen it induced high toxicity rates; therefore, it needs further investigation to preserve efficacy but reduce toxicity.
It is pretty clear that no matter how or when you take it, the ipi/nivo combo does much better than ipi or nivo alone. It is also clear that the side effects will be greater. Not news. However, the real news is still out there. Do melanoma peeps FAIL to progress more often when given treatment, in this case immunotherapy, BEFORE rendering them NED or giving them the treatment while some of their disease remains in place???? Inquiring minds NEED to KNOW!!!
Hang tough ratties. You teach us all. - c
No comments:
Post a Comment