Pathological response and survival with neoadjuvant therapy in melanoma: A pooled analysis from the International Neoadjuvant Melanoma Consortium (INMC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9503-9503 ◽  
Author(s):  
Alexander M. Menzies ◽  
Elisa A. Rozeman ◽  
Rodabe Navroze Amaria ◽  
Alexander Chan Chi Huang ◽  
Richard A. Scolyer ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Clinical Stage ◽  
Complete Response ◽  
Pooled Analysis ◽  
Stage Iii ◽  
Post Surgery ◽  
Neoadjuvant Immunotherapy ◽  
Neoadjuvant Systemic Therapy ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

9503 Background: Pathological complete response (pCR) to neoadjuvant systemic therapy (NST) correlates with survival, and is recognized as a path to regulatory approval in several cancers. Recent trials have reported that neoadjuvant immunotherapy (IT) and targeted therapy (TT) regimens achieve high pCR rates and impressive recurrence-free survival in stage III melanoma, however, the relationship between pCR, relapse-free (RFS) and overall survival (OS) in larger datasets of melanoma patients (pts) remains unknown. Methods: We pooled data from 6 modern NST clinical trials of anti-PD-1 based immunotherapy or BRAF/MEK targeted therapy conducted across institutions participating in the INMC. Pts with RECIST measurable, surgically resectable clinical stage III melanoma who underwent surgery were included. NST regimens included nivolumab (as monotherapy or in combination with ipilimumab), pembrolizumab or dabrafenib+trametinib. Baseline disease characteristics, treatment regimen, pCR and RFS were examined. Results: 184 pts with clinical stage III melanoma (AJCCv7: 100 IIIB, 84 IIIC) completed NST (133 IT, 51 TT) and underwent surgery. Median age was 57y (range 18-87). A pCR was observed in 41% of patients; 51 (38%) with IT and 24 (47%) with TT. Median follow-up post-surgery is 13 mo (95% CI 12-16); 10 mo with IT and 22 mo with TT. 44 (24%) pts have recurred (17 loco-regional, 21 distant, 6 both sites at first recurrence), 18 (14%) after IT and 26 (51%) after TT. 12-month RFS was improved with IT vs TT (83% vs 65%, p < 0.001). For those with pCR, 7% have recurred, 0/51 (0%) after IT, 7/17 (41%) after TT. For those without pCR, 34% have recurred, 18/82 (22%) after IT and 19/27 (70%) after TT. 12-month RFS was improved in those with pCR vs without pCR (95% vs 62%, p < 0.001), including in those with IT (100% vs 72%, p < 0.001) and TT (88% vs 43%, p < 0.001). 16 (9%) patients have died including two who had a pCR, both from TT. Conclusions: Neoadjuvant IT and TT are active regimens in resectable clinical stage III melanoma patients and are associated with high pCR rate. The ability to achieve pCR correlates with improved RFS and remarkably no patient with pCR from immunotherapy has recurred to date.

Preliminary results from the international neoadjuvant melanoma consortium (INMC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9581-9581 ◽  
Author(s):  
Alexander M. Menzies ◽  
Elisa A. Rozeman ◽  
Rodabe Navroze Amaria ◽  
Richard A. Scolyer ◽  
Michael T. Tetzlaff ◽  
...  
Keyword(s):  
Clinical Stage ◽  
Single Agent ◽  
Complete Response ◽  
Stage Iii ◽  
Resected Specimen ◽  
Neoadjuvant Immunotherapy ◽  
Immune Therapies ◽  
Hematoxylin And Eosin ◽  
Stage Iii Melanoma

9581 Background: For several cancers, response to neoadjuvant therapy (NAT) correlates with survival. Targeted and immune therapies achieve high response rates and durable survival in many patients with metastatic melanoma. Their role as NAT for stage III disease is not clear, and whether pathological response following NAT correlates with relapse-free (RFS) or overall survival (OS) in melanoma is unknown. Methods: Pooled clinical data from four ongoing NAT clinical trials (NCT02437279, NCT02231775, NCT02519322, NCT01972347) at three large melanoma centers participating in the INMC were examined. All trials included only patients with surgically resectable clinical stage III melanoma. NAT regimens included dabrafenib/trametinib (DT) and nivolumab (nivo) [single agent or in combination with ipilimumab (ipi/nivo)]. Patients who had undergone surgery prior to 27th January 2017 are included in this preliminary analysis. A pathological complete response (pCR) was defined as no viable melanoma cells in the resected specimen by hematoxylin and eosin evaluations by dedicated dermatopathologists. Results: 58 patients with clinical stage III melanoma (AJCCv7: 18 IIIB, 40 IIIC) have completed NAT and undergone surgery. 18 received neoadjuvant immunotherapy (IT): ipi/nivo x2 doses (N = 10), ipi/nivo x3 doses (N = 4) or nivo x4 doses (N = 4). 40 received neoadjuvant DT, either for two (N = 10) or three months (N = 30). Median age is 55 years (range 22-84). A pCR was observed in 50% of patients, 7 (39%) with IT and 22 (55%) with DT. Median follow-up is 10.2 months (95% CI 8.7-12.5). 14 (24%) patients have recurred (5 local, 8 distant, 1 both), 2 (11%) after IT, 12 (30%) after DT. For those with pCR, 14% have recurred, 0/7 (0%) after IT, 4/22 (18%) after DT. In contrast, for those without pCR, 34% have recurred, 2/11 (18%) after IT and 8/18 (44%) after DT. Two deaths have occurred, both after neoadjuvant TT. Early data suggests improved RFS in those with pCR. Conclusions: Neoadjuvant targeted and immunotherapy are active regimens in clinical stage III melanoma patients and are associated with high pCR rate. Preliminary data suggest pCR correlates with improved RFS. Updated data will be presented. Clinical trial information: NCT02437279, NCT02231775, NCT02519322, NCT01972347.

FDG-PET/CT response and outcome of neoadjuvant immunotherapy for clinical stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21569-e21569
Author(s):  
Milton Jose De Barros E. Silva ◽  
Caio Dabbous Liz ◽  
Marcos Rezende Teixeira ◽  
José Augusto Rinck ◽  
Monique Celeste Tavares ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Clinical Stage ◽  
Complete Response ◽  
The Other ◽  
Stage Iii ◽  
Mixed Response ◽  
Neoadjuvant Immunotherapy ◽  
Pet Ct ◽  
Stage Iii Melanoma ◽  
Fdg Pet Ct

e21569 Background: Neoadjuvant immunotherapy with nivolumab 3mg/kg and ipilimumab 1mg/kg for two cycles(N3+I1) or anti-PD1 for 3-8 weeks for clinical stage III melanoma have shown rates of pCR/near-pCR about 60% or 30%, respectively. The prognosis of this group seems to be excellent so far. On the other hand, patients classified as pathological non-response have a worse outcome and early identification of this group may allow us to tailor treatment before surgery. Methods: We conducted a retrospective analysis of patients with clinical stage III melanoma treated with neoadjuvant immune checkpoint blockade who did baseline and pre-operative FDG-PET/CT. The total number of FGD avid lesions and the percentual difference between the maximum SUV per lesion was calculated. The pathological results were correlated to FGD-PET/CT findings. Results: Between January 2019 and January 2021, nine patients with clinical stage III melanoma were identified. Six patients received Nivolumab 3m/kg and Ipilimumab 1mg/kg for two cycles and 3 received anti-PD1 for 60 days. Baseline FDG-PET/CT showed just one avid lesion in 7 patients, 2 avid lesions in one patient and 3 avid lesions in one patient. All known lesions identified by CT scan were also captured by FGD-PET/CT. After the neoadjuvant treatment, 4 patients achieved pCR/near-pCR. All of them were treated with N3+I1. Two of them had metabolic complete response (including the one with 3 PET- avid lesions) and 2 had reduction on FDG concentration (-31% and – 76%). Three patients had absence of response: 100% of viable tumor cells (VTC), all of them with increase in FDG concentration (+12% to + 307%) and appearance of a new lesion in one case. Two out of them were treated with anti-PD1. One patient had partial response (40% of VTC). Interestingly, this patient developed sarcoidosis-like reaction with increase of SUV in the index lesion (+68%) and appearance of mediastinal lymph-nodes. One patient, who had two lesions, presented a mixed response: complete response in one and 90% of VTC in the other. FDG-PET/CT was able to detect both responses (metabolic complete response and increase of FGD concentration of 17%, respectively). Conclusions: Reduction in FGD-PET/CT concentration with no appearance of new lesion(s) is associated with significant pathological response. An increase of SUV or appearance of new lesion(s) should be carefully interpreted.

Outcome of Clinical Stage III Melanoma Patients with FDG-PET and Whole-Body CT Added to the Diagnostic Workup

2013 ◽  
Vol 20 (9) ◽  
pp. 3098-3105 ◽  
Author(s):  
M. G. Niebling ◽  
E. Bastiaannet ◽  
O. S. Hoekstra ◽  
J. J. Bonenkamp ◽  
R. Koelemij ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Clinical Stage ◽  
Diagnostic Workup ◽  
Stage Iii ◽  
Whole Body ◽  
Whole Body Ct ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Body Ct

The prognostic role of metastatic lymph node immunological status in clinical stage III melanoma patients.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20103-e20103
Author(s):  
Piotr Rutkowski ◽  
Aleksandra Gos ◽  
Joost van den Oord ◽  
Monika Jurkowska ◽  
Katarzyna Szamotulska ◽  
...  
Keyword(s):  
Lymph Node ◽  
Metastatic Lymph Node ◽  
Clinical Stage ◽  
Stage Iii ◽  
Prognostic Role ◽  
Immunological Status ◽  
Metastatic Lymph ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

Bilateral facial neuritis associated with dabrafenib and trametinib after failure of neoadjuvant immunotherapy for stage III melanoma

2021 ◽  
Author(s):  
Andrew T. Li ◽  
Aung Min Maw ◽  
Edward Hsiao ◽  
Sydney Ch'ng ◽  
Georgina V. Long ◽  
...  
Keyword(s):  
Stage Iii ◽  
Neoadjuvant Immunotherapy ◽  
Stage Iii Melanoma

PP 3 S-100B concentrations predict disease specific survival in AJCC Stage III melanoma patients

2011 ◽  
Vol 47 ◽  
pp. S21
Author(s):  
S. Kruijff ◽  
E. Bastiaannet ◽  
M. Speijers ◽  
I. Kema ◽  
R. van Ginkel ◽  
...  
Keyword(s):  
Stage Iii ◽  
Disease Specific Survival ◽  
Ajcc Stage ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Disease Specific

Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9502-9502
Author(s):  
Rodabe Navroze Amaria ◽  
Michael A. Postow ◽  
Michael T. Tetzlaff ◽  
Merrick I. Ross ◽  
Isabella Claudia Glitza ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Clinical Stage ◽  
Pathologic Response ◽  
Stage Iii ◽  
Toxicity Profile ◽  
Radiographic Response ◽  
Recist 1.1 ◽  
Viable Tumor ◽  
Stage Iii Melanoma ◽  
Favorable Toxicity Profile

9502 Background: Neoadjuvant therapy (NT) for pts with clinical stage III melanoma remains an active area of research interest. Recent NT trial data demonstrates that achieving a pathologic complete response (pCR) correlates with improved relapse-free (RFS) and overall survival (OS). Checkpoint inhibitor (CPI) NT with either high or low dose ipilimumab and nivolumab regimens produces a high pCR rate of 30-45% but with grade 3-4 toxicity rate of 20-90%. In metastatic melanoma (MM), the combination of nivo with rela (anti Lymphocyte Activation Gene-3 antibody) has demonstrated a favorable toxicity profile and responses in both CPI-naïve and refractory MM. We hypothesized that NT with nivo + rela will safely achieve high pCR rates and provide insights into mechanisms of response and resistance to this regimen. Methods: We conducted a multi-institutional, investigator-initiated single arm study (NCT02519322) enrolling pts with clinical stage III or oligometastatic stage IV melanoma with RECIST 1.1 measurable, surgically-resectable disease. Pts were enrolled at 2 sites and received nivo 480mg IV with rela 160mg IV on wks 1 and 5. Radiographic response (RECIST 1.1) was assessed after completion of NT; surgery was conducted at wk 9 and specimens were assessed for pathologic response per established criteria. Pts received up to 10 additional doses of nivo and rela after surgery, with scans every 3 mo to assess for recurrence. The primary study objective was determination of pCR rate. Secondary objectives included safety, radiographic response by RECIST 1.1, event-free survival (EFS), RFS, and OS analyses. Blood and tissue were collected at baseline, at day 15, day 28, and at surgery for correlative analyses. Results: A total of 30 pts (19 males, median age 60) were enrolled with clinical stage IIIB/IIIC/IIID/IV (M1a) in 18/8/2/2 pts, respectively. 29 pts underwent surgery; 1 pt developed distant metastatic disease while on NT. pCR rate was 59% and near pCR ( < 10% viable tumor) was 7% for a major pathologic response (MPR, pCR + near pCR) of 66%. 7% of pts achieved a pPR (10-50% viable tumor) and 27% pNR (≥50% viable tumor). RECIST ORR was 57%. With a median follow up of 16.2 mos, the 1 -year EFS was 90%, RFS was 93%, and OS was 95%. 1-year RFS for MPR was 100% compared to 80% for non-MPR pts (p = 0.016). There were no treatment related gr 3/4 AEs that arose during NT; 26% of pts had a gr 3/4 AE that began during adjuvant treatment. Conclusions: Neoadjuvant and adjuvant treatment with nivo and rela achieved high pCR and MPR rates with a favorable toxicity profile in the neoadjuvant and adjuvant settings. Pts with MPR had improved outcomes compared to non-MPR pts. Translational studies to discern mechanisms of response and resistance to this combination are underway. Clinical trial information: NCT02519322.

Recurrent disease in patients with stage III melanoma in the era of adjuvant immune and targeted therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21570-e21570
Author(s):  
Victor Lo ◽  
Valerie Francescutti ◽  
Elaine McWhirter ◽  
Forough Farrokhyar ◽  
Linda May Lee
Keyword(s):  
Targeted Therapy ◽  
Adjuvant Therapy ◽  
Median Time ◽  
Adjuvant Treatment ◽  
Systemic Therapy ◽  
Recurrent Disease ◽  
Stage Iii ◽  
Recurrence Rates ◽  
Time To Recurrence ◽  
Stage Iii Melanoma

e21570 Background: Advancements in systemic therapy have reduced recurrence, and the adoption of nodal surveillance in place of dissection has reduced morbidity for patients with Stage III melanoma. The objective of this study was to describe the timing and pattern of recurrence in stage III melanoma patients and evaluate the impact of adjuvant treatment and nodal surveillance. Methods: A multicenter retrospective chart review of patients with pathologically confirmed Stage III cutaneous melanoma seen at either the Juravinski Cancer Centre or Walker Family Cancer Centre in Ontario, Canada from January 1, 2017 to December 31, 2019. Results: There were 137 patients with Stage III melanoma: 18% IIIA, 22% IIIB, 52% IIIC, and 8% Stage IIID as per the 8th American Joint Committee on Cancer (AJCC) 2018 staging system. 103 (75%) patients had sentinel lymph node biopsy (SLNB) only as part of initial surgical therapy, 6 (4%) had SLNB with completion dissection, and 25 (18%) had upfront radical nodal dissection. 67 (49%) patients received adjuvant therapy, of which 50 (74%) had immunotherapy, 17 (25%) received BRAF-targeted therapy, and 1 (1%) had interferon. 54 (39%) patients developed recurrent disease, with a median time to recurrence of 8.5 months (IQR: 4.3-14.9). The recurrence rates were 63% in patients who did not have adjuvant treatment and 37% in those who had adjuvant therapy, with a median time-to-recurrence of 7.5 and 9.0 months respectively. There were 30 (56%) loco-regional recurrences and 24 (44%) distant recurrences. Of the patients with loco-regional recurrence, 26 (87%) had SLNB only compared to 4 (13%) who had upfront or completion dissection. 12 (24%) patients recurred while on adjuvant treatment (7 distant recurrences and 5 loco-regional recurrences), and 8 (13%) patients recurred following completion of adjuvant treatment (5 distant recurrences and 3 loco-regional recurrences). Recurrences were detected by patients, clinicians, CT and nodal US surveillance in 43%, 20%, 28% and 9% of cases, respectively. The majority of loco-regional recurrence was detected clinically (67%) rather than by radiologic surveillance (33%). Of the 30 loco-regional recurrences, 24 underwent surgical resection of the recurrence, 4 had subsequent systemic therapy without surgery, 1 had intra-tumoral injections and 1 had no treatment. Conclusions: Recurrences in Stage III melanoma occur early, often within a year, with higher rates of loco-regional rather than distant disease. Recurrence rates were lower in those who received adjuvant therapy, but the majority of recurrences were detected by patients or clinicians, including loco-regional recurrences in patients who had SLNB only despite surveillance nodal US.

Neoadjuvant Versus Adjuvant Immune Checkpoint Blockade in the Treatment of Clinical Stage III Melanoma

2020 ◽  
Vol 27 (8) ◽  
pp. 2915-2926 ◽  
Author(s):  
Yun Song ◽  
Richard J. Straker ◽  
Xiaowei Xu ◽  
David E. Elder ◽  
Phyllis A. Gimotty ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Clinical Stage ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Stage Iii ◽  
Stage Iii Melanoma
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