Dabrafenib plus trametinib (D + T) as adjuvant treatment of resected BRAF-mutant stage III melanoma: Findings from the COMBI-AD trial analyzed based on AJCC 8 classification.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 9591-9591 ◽  
Author(s):  
James M. G. Larkin ◽  
Axel Hauschild ◽  
Mario Santinami ◽  
Victoria Atkinson ◽  
Mario Mandalà ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Stage Iii ◽  
Stage Iii Melanoma ◽  
Braf Mutant

Evaluation of patients with surgically resected high-risk melanoma receiving adjuvant therapy in routine clinical practice in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9577-9577
Author(s):  
Michael B. Atkins ◽  
Cristina Julian ◽  
Matthew H. Secrest ◽  
Janet Lee ◽  
Ana Maria Abajo Guijarro ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Checkpoint Inhibitors ◽  
The United States ◽  
Distant Recurrence ◽  
Advanced Melanoma ◽  
Stage Iii ◽  
Braf Mutations ◽  
Stage Iii Melanoma ◽  
Resected Stage ◽  
Braf Mutant

9577 Background: The management of patients with resected stage III melanoma has changed in recent years, and real-world data on recurrence patterns and adjuvant therapy responses are scarce. This study assessed adjuvant treatment patterns and outcomes in patients with advanced melanoma by BRAF status and relapse location. Methods: Patients diagnosed with stage III advanced melanoma between January 2011 and February 2020 in the nationwide Flatiron Health electronic health record–derived deidentified database were included if they were ≥18 years, received approved first-line (1L) adjuvant therapy after January 2018 with checkpoint inhibitors (CPIs; eg, nivolumab, pembrolizumab) or targeted therapies (TTs; eg, dabrafenib/trametinib), had 6 months’ follow-up and had ≥1 visit after starting adjuvant therapy (Cohort 1). Patients from Cohort 1 were included in Cohort 2 if they had a recurrence following initiation of adjuvant therapy, and those from Cohort 2 were included in Cohort 3 if they had a distant recurrence and available documented BRAF status at any time. Time to next systemic treatment (TTNT), overall survival (OS) and relapse free survival (RFS) were estimated using Kaplan-Meier (KM) methods from adjuvant therapy start (Cohort 1), first recurrence date (Cohort 2) or first distant recurrence date (Cohort 3). Results: Cohort 1 included 447 patients receiving 1L adjuvant therapy; Cohort 2 included patients after first distant (n = 47) or local (n = 35) relapse; Cohort 3 included distant-recurrent patients with tumors that were BRAF wild type (WT) (n = 22) or BRAF mutant (n = 23). The majority of patients were aged < 65 years. Across cohorts, relative use of TTs vs CPIs was similar: Cohort 1 (4.5% vs 96%), Cohort 2 (2.4% vs 98%) and Cohort 3 (2.2% vs 98%). Nivolumab was the most frequent treatment used across cohorts (84%-88%). In Cohort 1, 1- and 2-year KM probabilities for OS, RFS and TTNT were 93.5%/83.8%, 83.2%/70.6% and 84.0%/62.4%, respectively. In Cohort 2, for patients with local recurrence, 6- and 12-month OS probabilities were 93.4% and 78.8%, respectively, which were substantially higher than those for patients with distant recurrence (64.5% and 46.9%). In Cohort 3, for patients with documented BRAF mutations, 6- and 12-month OS rates from disease recurrence were 79.1% and 49.4%, respectively, which were greater than for those with BRAF-WT tumors (54.1% and 46.3%). Conclusions: Early RFS and OS outcomes for patients with surgically resected Stage III melanoma appear comparable to those reported in randomized clinical studies. The majority of patients with advanced melanoma, including patients who experienced recurrence, initiated treatment with CPIs. OS rates were numerically greater for Cohort 3 patients with BRAF-mutant tumors. Outcomes for patients with distant recurrence after adjuvant therapy remain unfavorable and represent a continued unmet medical need.

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.

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 indirect treatment comparison of the efficacy of pembrolizumab versus competing regimens for the adjuvant treatment of stage III melanoma

2019 ◽  
Vol 8 (1) ◽  
pp. 135-145 ◽  
Author(s):  
Maria Lorenzi ◽  
Stella Arndorfer ◽  
Raquel Aguiar-Ibañez ◽  
Emilie Scherrer ◽  
Frank Xiaoqing Liu ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Stage Iii ◽  
Indirect Treatment Comparison ◽  
Treatment Comparison ◽  
Indirect Treatment ◽  
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

scholarly journals Correction to: New paradigm for stage III melanoma: from surgery to adjuvant treatment

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Paolo Antonio Ascierto ◽  
Lorenzo Borgognoni ◽  
Gerardo Botti ◽  
Michele Guida ◽  
Paolo Marchetti ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Stage Iii ◽  
New Paradigm ◽  
Stage Iii Melanoma

Following publication of the original article [1], the authors reported that one of the authors, Corrado Caracò, has been accidentally omitted from the author list. In this Correction the author has been added to the author list.

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.

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