ASCO 2020: aanbevolen abstracten voor melanomen in alle stadia. Vooral veel met immuuntherapie of combinaties van verschillende medicijnen

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1 juni 2020: ASCO 2020

Hier een aantal aanbevolen abstracten specifiek voor melanomen van ASCO 2020. Aanbevolen door verschillende artsen / oncologen uit de praktijk (ook een oncoloog uit het Anthonie van Leeuwenhoek AvL Amsteram geeft zijn favoriete studies bij melanomen) en zijn vaak ook werkend voor ASCO zelf. Klik op de nummers voor de studiepublicaties en presentaties.

Aanbevolen door Ari VanderWalde MD, MPH, FACP

Session: Melanoma/Skin Cancers

10000 Pembrolizumab versus placebo after complete resection of high-risk stage III melanoma: New recurrence-free survival results from the EORTC 1325-MG/Keynote 054 double-blinded phase III trial at three-year median follow-up. S Dalle, AM Haydon, A Meshcheryakov, et al

Take-Home Message

Patients with resected high-risk stage III melanoma were randomized to receive pembrolizumab or placebo for 1 year or until disease progression or toxicity. After 3 years of follow-up, pembrolizumab was associated with a significantly prolonged recurrence-free survival (RFS) compared with placebo in the overall population and in patients with PD-L1–positive tumors. The RFS benefit was observed in all subgroups when patients were stratified by AJCC-7 stage and BRAF-V600 E/K–mutation status.
The use of pembrolizumab as adjunct therapy following resection of high-risk melanoma was associated with a durable improvement in RFS.

10001 Long-term benefit of adjuvant dabrafenib + trametinib (D+T) in patients (pts) with resected stage III BRAF V600–mutant melanoma: Five-year analysis of COMBI-AD. A Hauschild, R Dummer, M Santinami, et al

Take-Home Message

The authors report the 5-year outcomes following the use of adjuvant dabrafenib (D) plus trametinib (T) or placebo in patients with high-risk resected stage III BRAF V600E/K–mutant melanoma. Median recurrence-free survival (RFS) was not met in the D+T group versus 16.6 months in the placebo group (HR, 0.51). This RFS benefit was seen with D+T across all AJCC-7 substages. Median distant metastasis–free survival was not reached in either groups but favored D+T.
These results confirm the long-term clinical benefit of D+T in this population.

10002 First safety and efficacy results of PRADO: A phase II study of personalized response-driven surgery and adjuvant therapy after neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in resectable stage III melanoma. CU Blank, ILM Reijers, T Pennington, et al

Take-Home Message

Patients with stage III melanoma received two cycles of neoadjuvant ipilimumab 1 mg/kg and nivolumab 3 mg/kg (I1N3) following placement of a marker in the index lymph node (ILN). Resection of the ILN was completed at 6 weeks to allow the omission of therapeutic lymph node dissection (TLND) in patients achieving major pathologic response (MPR). MPR was observed in 60 patients (61%), and 58 of these did not undergo TLND. The estimated rate of grade 3/4 immune-related adverse events at 12 weeks was 24%.
The use of neoadjuvant I1N3 in patients with stage III melanoma was associated with a high response rate with manageable toxicity, which facilitated the omission of TLND in the majority of patients. Long-term survival outcomes are awaited.

10015 Twenty-four months RFS and updated toxicity data from OpACIN-neo: A study to identify the optimal dosing schedule of neoadjuvant ipilimumab (IPI) and nivolumab (NIVO) in stage III melanoma. EA Rozeman, ILM Reijers, EP Hoefsmit, et al

Take-Home Message

The authors present the updated 2-year outcomes of 86 patients with stage III melanoma with resectable lymph node metastasis randomized to three different dosing schedules of neoadjuvant ipilimumab (IPI) and nivolumab (NIVO). The median recurrence-free (RFS) and event-free survivals were not met in any of the treatment arms and were similar across the three treatment groups. The estimated 24-month RFS was 84% overall and 97% for patients achieving a pathologic response. Ongoing immune-related adverse events were observed at 2 years in 68% of patients.
Despite associated low-grade toxicity, the response to neoadjuvant IPI+NIVO in this population was durable. A phase III trials is warranted to compare neoadjuvant IPI1+NIVO3 and adjuvant anti-PD-1 therapy.

10016 Melanoma recurrence after adjuvant targeted therapy: A multicenter analysis. P Bhave, L Pallan, V Atkinson, et al

Take-Home Message

Patients with recurrent melanoma after adjuvant targeted therapy (TT) were followed to evaluate disease characteristics, treatment, and outcomes. The median time to first recurrence was 16.3 months. Systemic therapy at the first or subsequent recurrence was administered in 86% of patients. Treatments included anti-PD1–based therapy, ipilimumab monotherapy, and combination BRAF/MEK inhibitors. Among patients with disease that could be assessed for response, the response rate was 69.7% to anti-PD-1–based therapy, 46% to TT, and 9% to ipilimumab monotherapy. The respective 3-year overall survival rates were 79%, 55%, and 25%.
There may be a good response to subsequent immunotherapy among patients with melanoma who relapse after adjuvant TT.

10017 Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma. CL Slingluff, BA Blumenstein, KD Lewis, et al

Take-Home Message

The authors present the final data from part B1 of the MAVIS trial of patients with stage IIB–III resected cutaneous melanoma treated with seviprotimut-L or placebo. There were no treatment-related significant adverse events (AEs), and AEs led to discontinuation in 0.4% of patients in the treatment arm. There was a trend toward a recurrence-free survival (RFS) benefit with seviprotimut-L compared with placebo. However, a significant RFS benefit was seen in association with seviprotimut-L compared with placebo for patients aged <60 years and in those with stage IIB/C disease.
Seviprotimut-L was well-tolerated, and clinical benefit was observed in patients aged <60 years and in patents with stage IIB/C melanoma.

Aanbevolen door Zeynep Eroglu MD

Session: Melanoma/Skin Cancers

Take-Home Message

Patients with stage III melanoma received two cycles of neoadjuvant ipilimumab 1 mg/kg and nivolumab 3 mg/kg (I1N3) following placement of a marker in the index lymph node (ILN). Resection of the ILN was completed at 6 weeks to allow the omission of therapeutic lymph node dissection (TLND) in patients achieving major pathologic response (MPR). MPR was observed in 60 patients (61%), and 58 of these did not undergo TLND. The estimated rate of grade 3/4 immune-related adverse events at 12 weeks was 24%.
The use of neoadjuvant I1N3 in patients with stage III melanoma was associated with a high response rate with manageable toxicity, which facilitated the omission of TLND in the majority of patients. Long-term survival outcomes are awaited.

10006 Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies. A Sarnaik, NI Khushalani, J Alan, et al

Take-Home Message

This study evaluated the safety and efficacy of lifileucel (autologous adoptive cell therapy using tumor-infiltrating lymphocytes) in patients with unresectable metastatic melanoma who had progressed on checkpoint inhibitors and BRAF/MEK inhibitors. Tumors from 66 patients were resected and used for TIL production. TIL were cryopreserved after manufacture, shipped to study sites, and used for therapy.
Treatment with lifileucel resulted in a 36.4% ORR, and the median duration of response was not reached at 17.0 months of follow-up in advanced metastatic melanoma patients with a high baseline disease burden who progressed despite multiple prior therapies, including anti–PD-1 and BRAF/MEK inhibitors.

10007 Overall survival and biomarker analysis of a phase Ib combination study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) with axitinib in patients with metastatic mucosal melanoma. X Sheng, X Yan, Z Chi, et al

Take-Home Message

This study evaluated safety and clinical efficacy of toripalimab combined with axitinib in 33 patients with metastatic mucosal melanoma. Patients were treated with 1 or 3 mg/kg toripalimab every 2 weeks in combination with 5 mg axitinib twice daily until disease progression, unacceptable toxicity, or voluntary withdrawal. Among 29 treatment-naïve patients, 14 showed partial response and 11 had stable disease; the overall response rate was 48.3%. Median progression-free survival was 7.5 months; median overall survival was 20.7 months. Treatment-related adverse effects occurred in 97% of patients (39.4% were grade 3/4). Clinical response was strongly correlated with the gene expression profile (GEP) score of 12 different genes.
Toripalimab with axitinib is a promising treatment regimen for metastatic mucosal melanoma; GEP scores may predict response.

10008 Single-center phase I/Ib study of concurrent intrathecal (IT) and intravenous (IV) nivolumab (N) for metastatic melanoma (MM) patients (pts) with leptomeningeal disease (LMD). IC Glitza, S Phillips, C Brown, et al

Take-Home Message

This study evaluated the safety and maximum tolerated dose of intrathecal nivolumab (IT N) given with intravenous nivolumab (IV N) in metastatic melanoma patients with leptomeningeal disease. In the 15 patients who were treated with combination IT/IV N, the median number of IT N doses was four, with median OS of 46.1 weeks and a median follow-up of 18.7 weeks. Only four adverse events related to IT N occurred; no grade 3/4 events were observed.
The combination of IT/IV N is safe and well-tolerated in metastatic melanoma patients with leptomeningeal disease, and further investigation of the effects of this treatment is ongoing. IT administration of other immunotherapeutic agents warrants investigation.

vervolg aanbevolen abstracten specifiek voor melanomen op ASCO 2020

Aanbevolen door Dr. Roxana Dronca

Session: Melanoma/Skin Cancers

10004 Significant antitumor activity for low-dose ipilimumab (IPI) with pembrolizumab (PEMBRO) immediately following progression on PD1 Ab in melanoma (MEL) in a phase II trial. D Olson, JJ Luke, AS Poklepovic, et al

Take-Home Message

This prospective clinical trial initially enrolled 35 patients with advanced melanoma, no prior CTLA4 antibodies for metastatic disease, and who had progressed on PD-1 antibodies as immediate prior therapy (or a non–CTLA4 antibody combination). Patients were then treated with pembrolizumab 200 mg + ipilimumab 1 mg/kg every three weeks for four doses, then pembrolizumab alone for up to 2 years. The primary endpoint was response rate (RR) by irRECIST, which occurred in 10/22 evaluable patients. The trial was then expanded to 70 patients for further study. RR was 31% (21 of 67 evaluable patients). Due to several unconfirmed responses, the irRECIST response rate was 25%.
This study of pembrolizumab + ipilimumab demonstrated significant antitumor activity and tolerability in advanced melanoma following PD-1 antibody treatment.

10005 Ipilimumab (IPI) alone or in combination with anti-PD-1 (IPI+PD1) in patients (pts) with metastatic melanoma (MM) resistant to PD1 monotherapy. IP Da Silva, T Ahmed, S Lo, et al

Take-Home Message

This study retrospectively evaluated 330 patients with metastatic melanoma who were resistant to PD-1 and subsequently treated with ipilimumab (IPI) alone (161; 49%) or in combination with PD-1 (169; 51%) to assess response rate, survival, and predictors of both. Response rate overall was 12% with IPI alone and 31% with IPI + PD-1. Progression-free survival at 1 year was 13% with IPI alone and 27% with IPI + PD-1. Overall survival was 38% with IPI alone and 57% with IPI + PD-1. Best predictors of response and survival included treatment with IPI+PD-1 and several other factors.
IPI + PD-1 resulted in a higher response rate than IPI alone for patients with metastatic melanoma resistant to PD-1. High-grade toxicity was similar with both regimens.

Take-Home Message

This study evaluated the safety and efficacy of lifileucel (autologous adoptive cell therapy using tumor-infiltrating lymphocytes) in patients with unresectable metastatic melanoma who had progressed on checkpoint inhibitors and BRAF/MEK inhibitors. Tumors from 66 patients were resected and used for TIL production. TIL were cryopreserved after manufacture, shipped to study sites, and used for therapy.
Treatment with lifileucel resulted in a 36.4% ORR, and the median duration of response was not reached at 17.0 months of follow-up in advanced metastatic melanoma patients with a high baseline disease burden who progressed despite multiple prior therapies, including anti–PD-1 and BRAF/MEK inhibitors.

Take-Home Message

This study evaluated safety and clinical efficacy of toripalimab combined with axitinib in 33 patients with metastatic mucosal melanoma. Patients were treated with 1 or 3 mg/kg toripalimab every 2 weeks in combination with 5 mg axitinib twice daily until disease progression, unacceptable toxicity, or voluntary withdrawal. Among 29 treatment-naïve patients, 14 showed partial response and 11 had stable disease; the overall response rate was 48.3%. Median progression-free survival was 7.5 months; median overall survival was 20.7 months. Treatment-related adverse effects occurred in 97% of patients (39.4% were grade 3/4). Clinical response was strongly correlated with the gene expression profile (GEP) score of 12 different genes.
Toripalimab with axitinib is a promising treatment regimen for metastatic mucosal melanoma; GEP scores may predict response.

Take-Home Message

This study evaluated the safety and maximum tolerated dose of intrathecal nivolumab (IT N) given with intravenous nivolumab (IV N) in metastatic melanoma patients with leptomeningeal disease. In the 15 patients who were treated with combination IT/IV N, the median number of IT N doses was four, with median OS of 46.1 weeks and a median follow-up of 18.7 weeks. Only four adverse events related to IT N occurred; no grade 3/4 events were observed.
The combination of IT/IV N is safe and well-tolerated in metastatic melanoma patients with leptomeningeal disease, and further investigation of the effects of this treatment is ongoing. IT administration of other immunotherapeutic agents warrants investigation.

10013 Long-term survival from pembrolizumab (pembro) completion and pembro retreatment: Phase III KEYNOTE-006 in advanced melanoma. GV Long, J Schachter, A Arance, et al

Take-Home Message

This study evaluated long-term overall survival (OS) in patients with advanced melanoma who were treated with pembrolizumab (pembro) and retreated with pembro after disease progression, and compared them with patients receiving ipilimumab (ipi). Patients with advanced melanoma who had not previously been treated with ipi were randomized to receive pembro 10 mg/kg every 2 weeks or every 3 weeks for up to 2 years or ipi 3 mg/kg every 3 weeks for four doses. Patients who discontinued pembro at 2 years because of adequate response were eligible to receive up to 12 more months of pembro. OS at 36 months in the pembro group (n=103) was 100% among patients with complete response, 94.8% among patients with partial response, and 66.7% among patients with stable disease. Of the 15 patients who received a second course of pembro, the median time between pembro courses was 24.5 months.
Pembrolizumab improved OS in advanced melanoma patients compared with ipilimumab, and all patients who completed pembro treatment with a complete response were alive at 5 years.

10021 The IMPemBra trial, a phase II study comparing pembrolizumab with intermittent/short‐term dual MAPK pathway inhibition plus pembrolizumab in melanoma patients harboring the BRAFV600 mutation. EA Rozeman, JM Versluis, K Sikorska, et al

Take-Home Message

This study evaluated the optimal duration of treatment with trametinib (MAPKi) plus dabrafenib (BRAFi) in combination with pembrolizumab (anti–PD-1) in BRAFV600-mutated melanoma patients. The study assessed the regimen relative to its safety, feasibility, and immune-activating capacity. Treatment-naïve patients were started on pembrolizumab and randomized at 6 weeks to continue PEM only (cohort 1), or to receive, in addition to PEM, dabrafenib (D) plus trametinib (T) 2 x 1 week (cohort 2), 2 x 2 weeks (cohort 3), or continuously for 6 weeks (cohort 4). PEM was given up to 2 years in all cohorts. Grade 3/4 adverse events were observed in 12%, 12%, 50%, and 62% of patients in cohorts 1–4, respectively. ORR at week 18 was 62%, 75%, 75%, and 50% in cohorts 1–4, respectively. The median PFS in the PEM monotherapy group was 10.6 months compared with 27 months for the patients receiving PEM and short-term D+T.
Short term, intermittent D+T in combination with PEM was effective and more tolerable than continuous therapy with all three agents and warrants further investigation in a larger cohort.

Aanbevolen door Alexander CJ van Akkooi MD, PhDm (AvL Amsterdam)

Session: Melanoma/Skin Cancers

Take-Home Message

Patients with resected high-risk stage III melanoma were randomized to receive pembrolizumab or placebo for 1 year or until disease progression or toxicity. After 3 years of follow-up, pembrolizumab was associated with a significantly prolonged recurrence-free survival (RFS) compared with placebo in the overall population and in patients with PD-L1–positive tumors. The RFS benefit was observed in all subgroups when patients were stratified by AJCC-7 stage and BRAF-V600 E/K–mutation status.
The use of pembrolizumab as adjunct therapy following resection of high-risk melanoma was associated with a durable improvement in RFS.

Take-Home Message

The authors report the 5-year outcomes following the use of adjuvant dabrafenib (D) plus trametinib (T) or placebo in patients with high-risk resected stage III BRAF V600E/K–mutant melanoma. Median recurrence-free survival (RFS) was not met in the D+T group versus 16.6 months in the placebo group (HR, 0.51). This RFS benefit was seen with D+T across all AJCC-7 substages. Median distant metastasis–free survival was not reached in either groups but favored D+T.
These results confirm the long-term clinical benefit of D+T in this population.

Take-Home Message

Patients with stage III melanoma received two cycles of neoadjuvant ipilimumab 1 mg/kg and nivolumab 3 mg/kg (I1N3) following placement of a marker in the index lymph node (ILN). Resection of the ILN was completed at 6 weeks to allow the omission of therapeutic lymph node dissection (TLND) in patients achieving major pathologic response (MPR). MPR was observed in 60 patients (61%), and 58 of these did not undergo TLND. The estimated rate of grade 3/4 immune-related adverse events at 12 weeks was 24%.
The use of neoadjuvant I1N3 in patients with stage III melanoma was associated with a high response rate with manageable toxicity, which facilitated the omission of TLND in the majority of patients. Long-term survival outcomes are awaited.

Take-Home Message

The authors present the updated 2-year outcomes of 86 patients with stage III melanoma with resectable lymph node metastasis randomized to three different dosing schedules of neoadjuvant ipilimumab (IPI) and nivolumab (NIVO). The median recurrence-free (RFS) and event-free survivals were not met in any of the treatment arms and were similar across the three treatment groups. The estimated 24-month RFS was 84% overall and 97% for patients achieving a pathologic response. Ongoing immune-related adverse events were observed at 2 years in 68% of patients.
Despite associated low-grade toxicity, the response to neoadjuvant IPI+NIVO in this population was durable. A phase III trials is warranted to compare neoadjuvant IPI1+NIVO3 and adjuvant anti-PD-1 therapy.

10016 Melanoma recurrence after adjuvant targeted therapy: A multicenter analysis. P Bhave, L Pallan, V Atkinson, et al

Take-Home Message

Patients with recurrent melanoma after adjuvant targeted therapy (TT) were followed to evaluate disease characteristics, treatment, and outcomes. The median time to first recurrence was 16.3 months. Systemic therapy at the first or subsequent recurrence was administered in 86% of patients. Treatments included anti-PD1–based therapy, ipilimumab monotherapy, and combination BRAF/MEK inhibitors. Among patients with disease that could be assessed for response, the response rate was 69.7% to anti-PD-1–based therapy, 46% to TT, and 9% to ipilimumab monotherapy. The respective 3-year overall survival rates were 79%, 55%, and 25%.
There may be a good response to subsequent immunotherapy among patients with melanoma who relapse after adjuvant TT.

Take-Home Message

The authors present the final data from part B1 of the MAVIS trial of patients with stage IIB–III resected cutaneous melanoma treated with seviprotimut-L or placebo. There were no treatment-related significant adverse events (AEs), and AEs led to discontinuation in 0.4% of patients in the treatment arm. There was a trend toward a recurrence-free survival (RFS) benefit with seviprotimut-L compared with placebo. However, a significant RFS benefit was seen in association with seviprotimut-L compared with placebo for patients aged <60 years and in those with stage IIB/C disease.
Seviprotimut-L was well-tolerated, and clinical benefit was observed in patients aged <60 years and in patents with stage IIB/C melanoma.

ASCO 2020, aanbevolen abstracten melanomen, immuuntherapie