Neoadjuvant ipilimumab + nivolumab (IPI+NIVO) in palpable stage III melanoma: Updated data from the OpACIN trial and first immunological analyses.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9586-9586 ◽  
Author(s):  
Elisa A. Rozeman ◽  
Christian U. Blank ◽  
Alexander Christopher Jonathan Van Akkooi ◽  
Pia Kvistborg ◽  
Lorenzo Fanchi ◽  
...  
Keyword(s):  
T Cell ◽  
High Risk ◽  
Adjuvant Treatment ◽  
Stage Iv ◽  
Study Data ◽  
Stage Iii ◽  
Feasibility Trial ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Grade 3

9586 Background: The combination of IPI+NIVO induces high response rates and improved overall survival in late stage melanoma. T cell checkpoint inhibition is of greatest value at the moment of TCR triggering and therefore dependent on the amount of antigen present, indicating that adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. Methods: Two-arm Phase 1b feasibility trial of 20 high risk AJCC stage IIIB and IIIC melanoma patients with palpable nodal disease receiving the combination of IPI 3mg/kg and NIVO 1mg/kg, either adjuvant four courses after surgery, or split two courses neo-adjuvant and two courses adjuvant. Results: In this update all 20 patients are evaluable. Neo-adjuvant application of IPI+NIVO was feasible and no surgery-associated adverse events were attributed to (neo-)adjuvant therapy. 18/20 patients had to stop early due to grade 3/4 toxicities. Neo-adjuvant IPI+NIVO reduced tumor load in 8/10 patients (3 pCR, 4 near-pCRs [minimal remaining micrometastases], 1 pPR [75% reduction], 1 SD and 1 PD). To date, after a median follow-up of 45 weeks (range 13-74), none of the responders in the neoadjuvant arm has relapsed. Relapse was observed for both non-responders within the neo-adjuvant arm and for 3 patients within the adjuvant arm. TCR sequencing and MHC tetramer-based analysis to compare the induction and expansion of tumor (neo-)antigen-specific T cell responses between both treatment arms are underway and will be presented. Conclusions: The combination of IPI+NIVO in the (neo-)adjuvant treatment setting for high risk stage III melanoma patients is feasible and induces very frequent responses. At the same time, severe grade 3/4 toxicity is more frequent than expected from stage IV melanoma patient study data. These results indicate that IPI+NIVO is a promising combination for neo-adjuvant treatment in stage III melanoma. Adjusted combination schemes are currently tested in the phase 2 OpACIN-neo trial, with the aim of reducing toxicity while preserving efficacy. Clinical trial information: NCT02437279.

scholarly journals Cost-effectiveness of pembrolizumab for the adjuvant treatment of resected high-risk stage III melanoma in the United States

2019 ◽  
Vol 22 (10) ◽  
pp. 981-993 ◽  
Author(s):  
Arielle G. Bensimon ◽  
Zheng-Yi Zhou ◽  
Madeline Jenkins ◽  
Yan Song ◽  
Wei Gao ◽  
...  
Keyword(s):  
United States ◽  
Cost Effectiveness ◽  
High Risk ◽  
Adjuvant Treatment ◽  
The United States ◽  
Stage Iii ◽  
Stage Iii Melanoma

scholarly journals An Economic Evaluation of Pembrolizumab Versus Other Adjuvant Treatment Strategies for Resected High-Risk Stage III Melanoma in the USA

2020 ◽  
Vol 40 (7) ◽  
pp. 629-643 ◽  
Author(s):  
Arielle G. Bensimon ◽  
Zheng-Yi Zhou ◽  
Madeline Jenkins ◽  
Yan Song ◽  
Wei Gao ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
High Risk ◽  
Adjuvant Treatment ◽  
Treatment Strategies ◽  
Stage Iii ◽  
The Usa ◽  
Stage Iii Melanoma

Multi-institutional, prospective, randomized, double-blind, placebo-controlled phase IIb trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine to prevent recurrence in high-risk melanoma patients: A subgroup analysis.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 63-63
Author(s):  
Robert Connor Chick ◽  
Mark B. Faries ◽  
Diane F. Hale ◽  
Phillip M. Kemp Bohan ◽  
Annelies Hickerson ◽  
...  
Keyword(s):  
High Risk ◽  
Subgroup Analysis ◽  
Stage Iv ◽  
Stage Iii ◽  
Tumor Lysate ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Melanoma Patients ◽  
Resected Stage ◽  
Disease Free

63 Background: A novel vaccine strategy may prevent recurrence in high-risk melanoma patients (pts). The TLPLDC vaccine uses yeast cell wall particles (YCWP) to load tumor lysate into autologous dendritic cells (DC). In this phase IIb trial of TLPLDC vs. placebo in resected stage III/IV pts, TLPLDC increased 24 month (mo) disease free survival (DFS) in the per treatment (PT) population. Here, we present a 24mo DFS subgroup analysis and estimated overall 36mo DFS. Methods: Disease-free pts were randomized 2:1 to the TLPLDC vaccine vs. unloaded YCWP+DC at 0, 1, 2, 6, 12, and 18mo. The protocol was amended to allow concurrent adjuvant checkpoint inhibitor (CPI) therapy once approved. The pre-specified PT population included only pts completing the primary vaccine/placebo series (PVS) at 6 mo. Kaplan-Meier estimates of DFS were used to compare treatment arms by stage (III or IV) and CPI therapy (yes/no) in the ITT and PT populations. Results: 144 pts were randomized (103 TLPLDC, 41 placebo); 98 pts (66 TLPLDC, 32 placebo) completed the PVS. There were no clinicopathologic differences between treatment groups. There was no difference in 24mo DFS in stage III pts (n = 112), but in stage IV pts (n = 32), the 24mo DFS was 44% vs 0% (TLPLDC vs placebo) (p = 0.41) in ITT and 73.3% vs. 0% (HR 0.14, p = 0.002) in PT. Stage IV pts were more likely to receive CPI than stage III pts (50% vs. 30%, p = 0.003). There was no difference in 24mo DFS for pts who did not receive CPI (n = 102), but in pts who received CPI (n = 42), the 24mo DFS was 49.3% vs. 31.3% (p = 0.71) in ITT and 68.8% vs. 41.7% (HR 0.46, p = 0.28) in PT, showing a trend toward improved DFS in pts who completed the PVS and received CPI (n = 31). Overall, the 36mo estimated DFS was 34.2% vs. 21.6% (p = 0.89) for ITT and 56.9% vs. 27.9% (p = 0.021) for PT. Conclusions: The TLPLDC vaccine improved DFS in patients completing the PVS at 24 and 36 mos, particularly in the resected stage IV subset. The apparent synergistic effect with TLPLDC + CPI will be confirmed in a phase III study evaluating adjuvant TLPLDC + CPI vs. CPI alone in resected stage IV melanoma pts. Clinical trial information: NCT02301611.

Abstract A14: Surgical removal of metastatic lesions increases T-cell reactivity to tumor-associated antigens in stage III melanoma patients

2018 ◽  
Author(s):  
Yago Pico de Coaña ◽  
Fríða Björk Gunnarsdóttir ◽  
Maria Wolodarski ◽  
Suzanne Egyhazi Brage ◽  
Giuseppe Masucci ◽  
...  
Keyword(s):  
T Cell ◽  
Stage Iii ◽  
Surgical Removal ◽  
Cell Reactivity ◽  
Tumor Associated Antigens ◽  
Metastatic Lesions ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
T Cell Reactivity

Cost-effectiveness of interferon for high-risk (stage III) melanoma patients

1999 ◽  
Vol 35 ◽  
pp. S372
Author(s):  
V. Guillem ◽  
M. Alvarez-Mon ◽  
F. Camacho ◽  
J.L. Diaz-Perez ◽  
E. Diaz-Rubio ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
High Risk ◽  
Stage Iii ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

Induction chemotherapy followed by chemoradiotherapy and TME for high-risk locally advanced rectal cancer with and without synchronous resectable metastases.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 599-599 ◽  
Author(s):  
Carla Hajj ◽  
Martin R. Weiser ◽  
Aoife McErlean ◽  
Marc Gollub ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Stage Iv ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Iii ◽  
Primary Tumors ◽  
Grade 3

599 Background: Induction chemotherapy (ICT) followed by chemoradiation (CRT) may improve tumor downsizing and disease control among patients (pts) with locally advanced rectal cancer (LARC). We retrospectively assessed the safety and short-term efficacy of ICT followed by CRT and total mesorectal excision (TME) in pts with high-risk LARC with or without synchronous resectable metastases. Methods: We reviewed records of 44 consecutive stage III (n=23) or stage IV synchronous (n=27) pts with LARC treated with ICT followed by CRT between 12/06 – 12/10. Pts had high-risk primary tumors based on advanced T and/or N stage by endorectal ultrasound and/or MRI: T3 (n= 35), T4 (n=7) and N1 (N=18), N2 (n=19). Recurrence-free (RFS) and overall survival (OS) were estimated by Kaplan-Meier methods. Results: Median age was 52 yrs, 66% were female. Pts received a median of 6 cycles of 5-FU based ICT combined with oxaliplatin (n=44). CRT (median dose 50.4 Gy) was delivered with continuous infusion 5-FU; two pts did not complete the prescribed CRT. During induction CT, 10 (22.7%) pts experienced grade 3+ neutropenia. Grade 3+ neutropenia or GI toxicity occurred in 3 (6.8%) and 3 (6.8%) pts, respectively during CRT. Imaging or endoscopic assessment showed that 35 pts had disease regression after ICT, whereas 1 pt progressed and 2 had stable disease. Response to ICT was not assessed in 6 pts. 7 pts did not undergo surgery due to: progression of disease (n=2); comorbid disease (n=2); or pt refusal (n=3). 37 pts proceeded to TME including 17 with known distant metastasis, 16 of whom underwent metastasectomy. 17 pts had tumor response > 90% including 8 with pathologic CR. With a median follow-up of 29.4 mos, 1 pt who underwent TME developed local recurrence. Amongst the 9 pts who had distant recurrences, 7 had initial stage IV disease. The 3-yr RFS among the resected stage III pts was 95%; the 3-yr OS for stage III pts and stage IV pts were 100% and 80% respectively. Conclusions: In this retrospective series, ICT prior to CRT was associated with acceptable toxicity and a substantial incidence of tumor regression. OS and RFS appear promising in this high-risk group of patients.

The use of PET/CT to detect early recurrence after resection of high-risk stage III melanoma, prior to the start of adjuvant therapy and during follow-up.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22039-e22039
Author(s):  
Bernies Van Der Hiel ◽  
Emma H.A. Stahlie ◽  
Marcel P Stokkel ◽  
Michel W.J.M. Wouters ◽  
Yvonne Schrage ◽  
...  
Keyword(s):  
High Risk ◽  
Adjuvant Therapy ◽  
Complete Resection ◽  
Stage Iiib ◽  
Stage Iii ◽  
Asymptomatic Patients ◽  
Pet Ct ◽  
Melanoma Patients ◽  
Stage Iii Melanoma

e22039 Background: To date, international consensus concerning the use of PET/CT as a surveillance tool in the follow-up of high-risk melanoma patients after complete resection of disease is lacking. Moreover, with the rise of adjuvant therapy it seems appropriate to investigate the role of this imaging modality to exclude newly developed metastases after resection and prior to starting treatment. The aim of this study was to investigate the use of PET/CT as surveillance tool in the follow-up and prior to adjuvant therapy in asymptomatic patients with complete resection of stage IIIB and IIIC melanoma. Methods: Prospectively two cohorts were set up with stage III melanoma patients with complete resection of disease. In the first cohort (stage IIIB/C AJCC 7th) surveillance PET/CT was performed 6-monthly for two years if patients stayed asymptomatic with normal serum S100B, with a final scan at three years. In the second cohort (stage IIIB/C/D AJCC 8th) patients underwent one screening PET/CT after resection and prior to starting adjuvant treatment. Results: Eighty patients entered follow-up in cohort 1. Of these, the majority did not undergo surveillance scans, because they required treatment for newly detected clinical metastases. Thirty-five patients remained asymptomatic and were included in surveillance cohort one (105 scans) with a median follow-up of 33 months. Twelve patients (34%) developed a recurrence, seven (20%) of which were detected on the first scan at six months. Seven recurrences involved stage IIIC patients, five stage IIIB patients. Sensitivity and specificity were 92% and 100% respectively. Forty-two patients were included in cohort 2. Recurrence was suspected on nine scans, four (10%) of which were true positive. One patient proceeded to undergo a node dissection and then started adjuvant therapy. The other three patients had progressed to stage IV and therefore started radiotherapy and/or systemic immunotherapy. Five (12%) scans were false positive, the suspected lesions were not related to the preceded surgery. The number of scans needed to find one asymptomatic recurrence were 8.8 and 10.5 in cohort one and two, respectively. Conclusions: This study shows that PET/CT is a useful surveillance tool for detecting recurrence in asymptomatic high-risk resected stage III melanoma patients, especially within the first six months after surgery and therefore should be considered when monitoring these patients during follow-up as well as prior to starting adjuvant therapy.

scholarly journals Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications

2021 ◽  
Vol 22 (9) ◽  
pp. 4561
Author(s):  
Luca Tonella ◽  
Valentina Pala ◽  
Renata Ponti ◽  
Marco Rubatto ◽  
Giuseppe Gallo ◽  
...  
Keyword(s):  
High Risk ◽  
Predictive Biomarkers ◽  
Stage Iii ◽  
Skin Cancers ◽  
Immune Therapies ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Improve Patient Management ◽  
Patient Prognosis

Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.

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