Neoadjuvant ipi/nivo as well as Neoadjuvant BRAF targeted therapy for unresectable melanoma lesions

Could neoadjuvant treatment (melanoma treatment administered BEFORE a lesion is surgically removed or radiated) be the way of future melanoma treatment???  Here's the data so far: Neoadjuvant reports related to melanoma

Now, there's this~

Successful Treatment of Unresectable Advanced Melanoma by Administration of Nivolumab With Ipilimumab Before Primary Tumor Resection.  Fujimura, Kambayashi, Sato, et al.  Front Med (Lausanne). 2019 Jun 26.

Ipilimumab, in combination with nivolumab, is one of the promising drugs that enhance the anti-tumor immune response of patients with advanced melanoma. Since the co-administration of nivolumab with ipilimumab in the neoadjuvant setting expands melanoma-reactive T cells at the primary site of melanoma and has a high rate of histological complete response, the pre-surgical administration of this combination could be the optimal therapy for unresectable advanced melanoma. In this report, a case of unresectable advanced melanoma treated successfully with administration of nivolumab with ipilimumab before primary tumor resection is presented. In addition, CD8+ T cells increased among the tumor-infiltrating lymphocytes that were surrounding melanoma cells and caspase 3+ cells. The present case suggests that pre-surgical administration of nivolumab with ipilimumab could be the optimal therapy for the treatment of unresectable advanced melanoma.

Neoadjuvant BRAF-targeted therapy in regionally advanced and oligometastatic melanoma.  Eroglu, Eatrides, Naqvi, et al. Pigment Cell Melanoma Res. 2019 Jul 22. 

Current management of locoregional and oligometastatic melanoma is typically with surgery; however, some patients are unable to undergo resection due to location/size of their tumors and/or the anticipated morbidity of the surgery. While there are currently no established guidelines for neoadjuvant therapy in melanoma, neoadjuvant BRAF-targeted therapy may make resection more feasible.

A retrospective analysis was conducted of 23 patients with BRAFV600-mutant, stage III/IV melanoma treated with BRAF-targeted therapy prior to surgery, with no adjuvant treatment. Surgical specimens, preoperative imaging and clinical outcomes were evaluated.

Ten of 23 patients (44%) attained a pathologic complete response (pCR), with no correlation between RECIST-response based on preoperative imaging and pathologic response. After a median of 43 months follow-up, only 1 patient (10%) with a pCR recurred; while 8 of 13 (62%) patients without a pCR recurred. Patients with a pCR had significantly improved relapse-free (RFS) and overall survival (OS) compared to patients with residual tumor.

Neoadjuvant BRAF-targeted therapy is associated with a high pCR rate in patients with stage III-IV melanoma, which may correlate with improved RFS and OS. 

Overall, still early days, but neoadjuvant treatment may be very good news for many melanoma patients, especially those for whom surgery is not an option.  Hang tough ratties!!  ~ c