ASCO 2021: aanbevolen abstracten voor melanomen in alle stadia. Vooral veel met immuuntherapie of combinaties van verschillende medicijnen

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5 juni 2021: ASCO 2021

Hier een aantal aanbevolen abstracten specifiek voor melanomen van ASCO 2021. Aanbevolen door verschillende artsen / oncologen uit de praktijk en zijn vaak ook werkend voor ASCO zelf. Klik op de nummers voor de studiepublicaties en presentaties.

Aanbevolen door Ari VanderWalde MD, MPH, FACP

Oral Abstract Session: Melanoma/Skin Cancers
Sunday, June 6, 2021; 8:00 AM–11:00 AM EDT

9501 Final analysis of overall survival (OS) and relapse-free-survival (RFS) in the intergroup S1404 phase III randomized trial comparing either high-dose interferon (HDI) or ipilimumab to pembrolizumab in patients with high-risk resected melanoma. KF Grossmann, M Othus, SP Patel, et al

Take-Home Message

The effectiveness of pembrolizumab for the treatment of patients with high-risk resected melanomas was compared with standard-of-care regimens (HDI or ipilimumab). Recurrence-free survival (RFS) was statistically improved in the pembrolizumab group (HR, 0.740; 99.618% CI, 0.571–0.958), while overall survival (OS) was not, both for the overall patient population (HR, 0.837; 96.3% CI, 0.622–1.297) and the PD-L1+ patient population (HR, 0.883; 97.8% CI, 0.604–1.291). HDI and ipilimumab were associated with higher rates of grade 3 adverse events (69% and 43%, respectively) than pembrolizumab (17%).

Compared with the standard-of-care regimens, pembrolizumab was better tolerated and improved RFS but not OS.

9503 Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047). EJ Lipson, HA-H Tawbi, D Schadendorf, et al

Take-Home Message

This study evaluated whether a fixed-dose combination treatment targeting two potentially synergistic immune checkpoint pathways (LAG-3 and PD-1 by relatlimab and nivolumab, respectively) would provide a better benefit–risk profile than monotherapy. The relatlimab plus nivolumab group had significantly longer progression-free survival (PFS; 10.1 months) than the nivolumab group (4.6 months). However, it also had a higher rate of grade 3–4 treatment-related adverse events (18.9% vs 9.7%).

Compared with nivolumab alone, the relatlimab plus nivolumab fixed-dose combination had a significant PFS benefit, indicating that dual inhibition might be a promising strategy. The therapy was also well-tolerated, and the treatment-related adverse events were manageable.

9506 CheckMate 067: 6.5-year outcomes in patients (pts) with advanced melanoma. JD Wolchok, V Chiarion-Sileni, R Gonzalez, et al

Take-Home Message

Patients with unresectable stage III or IV melanoma were treated with nivolumab (NIVO) plus ipilimumab (IPI), NIVO alone, or IPI alone. At the 6.5-year follow-up, NIVO + IPI was associated with longer median overall survival (OS; 72.1 months for the combination vs 36.9 months for NIVO and 19.9 months for IPI), a longer median treatment-free interval (27.6 months vs 2.3 months and 1.9 months), a lower percentage of patients who received subsequent systemic therapy (36% vs 49% and 66%), and a higher percentage of patients who were off treatment and never received subsequent therapy (81% vs 74% and 43%). However, more grade 3/4 treatment-associated adverse events were reported for the NIVO + IPI group (59%) than the other two groups (24% for NIVO and 28% for IPI).

There was an increased benefit in using NIVO + IPI versus NIVO or IPI alone in terms of overall survival, progression-free survival, and objective response rate.

Aanbevolen door dr. van Akkooij uit AvL - Amsterdam

Poster Session: Melanoma/Skin Cancers
Available Starting on Friday, June 4, 2021; 9:00 EDT

9563 External validation of a Dutch predictive nomogram for complete response to T-VEC in an independent American patient cohort. EHA Stahlie, M Carr, JS Zager, et al

Take-Home Message

This study aimed to validate a model that uses tumor size and type and number of metastases to predict a complete response in T-VEC–treated stage IIIb/IVM1a melanoma patients.

The nomogram was externally validated using an independent dataset and supports the use of T-VEC early in the melanoma disease course when tumor burdens are low.

9575 Postoperative radiotherapy in Merkel cell carcinoma (MCC). S Levy, S Blankenstein, DJ Grunhagen, et al

Take-Home Message

In this retrospective study, the effects of postoperative radiotherapy on stage I–III Merkel cell carcinoma (MCC) patient survival were assessed. Postoperative radiotherapy did not improve disease-specific survival in stage I–III MCC patients; recurrence-free survival was improved in stage III MCC only. Propensity score matching indicated no bias.

In contrast to current guidelines, postoperative radiotherapy has limited effect on recurrence-free survival and no effect on disease-specific survival in MCC patients.

9579 The prognostic value of the interferon-gamma (IFNγ) signature in patients with macroscopic stage III melanoma treated with and without adjuvant systemic therapy. JM Versluis, S Blankenstein, P Dimitriadis, et al

Take-Home Message

In this study, the efficacy of adjuvant anti–PD-1 therapy in macroscopic stage III melanoma tumor–resected patients and the potential for IFNg as a prognostic indicator in these patients was assessed. Overall survival was not reached in either pre-adjuvant anti–PD-1 or adjuvant anti–PD-1–treated patients but trended toward a benefit in adjuvant-treated patients. Recurrence-free survival was enhanced after adjuvant treatment (22.8 months vs 6.1 months). Transcriptome sequencing revealed improved recurrence-free survival in patients with no adjuvant therapy and in both high and low IFNg–expressing adjuvant anti–PD-1–treated patients.

The activity of adjuvant anti–PD-1 in patients with macroscopic stage III melanoma was confirmed and indicates a potential for IFNg as a prognostic indicator for patient outcomes.

Oral Abstract Session: Melanoma/Skin Cancers
Sunday, June 6, 2021; 8:00 AM–11:00 AM EDT

9500 Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma. AM Eggermont, A Meshcheryakov, V Atkinson, et al

Take-Home Message

In this update from the EORTC 1325-MG/Keynote-054 phase III trial, patients with recurrent pembrolizumab-treated stage III cutaneous melanoma received pembrolizumab 200 mg IV every 3 weeks for a maximum of 2 years for crossover or rechallenge or until disease progression or toxicity.

Evaluable crossover patients demonstrated a 39% ORR and 32% 3-year progression-free survival rate; rechallenge efficacy was limited.

Take-Home Message

The effectiveness of pembrolizumab for the treatment of patients with high-risk resected melanomas was compared with standard-of-care regimens (HDI or ipilimumab). Recurrence-free survival (RFS) was statistically improved in the pembrolizumab group (HR, 0.740; 99.618% CI, 0.571–0.958), while overall survival (OS) was not, both for the overall patient population (HR, 0.837; 96.3% CI, 0.622–1.297) and the PD-L1+ patient population (HR, 0.883; 97.8% CI, 0.604–1.291). HDI and ipilimumab were associated with higher rates of grade 3 adverse events (69% and 43%, respectively) than pembrolizumab (17%).

Compared with the standard-of-care regimens, pembrolizumab was better tolerated and improved RFS but not OS.

9502 Neoadjuvant and adjuvant nivolumab (nivo) with anti-LAG3 antibody relatlimab (rela) for patients (pts) with resectable clinical stage III melanoma. RN Amaria, MA Postow, MT Tetzlaff, et al

Take-Home Message

This study aimed to determine whether neoadjuvant therapy (NT) delivered in combination with nivolumab plus relatlimab treatment could reduce toxicity while maintaining pathologic complete response in stage III/IV M1a melanoma patients. No grade 3/4 treatment-associated adverse events were reported during NT; 26% of patients reported treatment-associated adverse events during adjuvant treatment. Patient outcomes (major pathologic response [pCR + near pCR, 66%], ORR [57%], event-free survival [90%], recurrence-free survival [93%], and overall survival [95%]) were not impacted.

Nivolumab plus relatlimab treatment was well-tolerated in metastatic melanoma patients without a reduction in NT benefits to patient outcomes.

Aanbevolen door Roxana Dronca MD Associate Professor of Oncology, Chair of the Mayo Clinic Division of Hematology/Oncology, and a Consultant in the Division of Hematology/Oncology

Oral Abstract Session: Melanoma/Skin Cancers
Sunday, June 6, 2021; 8:00 AM–11:00 AM EDT

Take-Home Message

In this update from the EORTC 1325-MG/Keynote-054 phase III trial, patients with recurrent pembrolizumab-treated stage III cutaneous melanoma received pembrolizumab 200 mg IV every 3 weeks for a maximum of 2 years for crossover or rechallenge or until disease progression or toxicity.

Evaluable crossover patients demonstrated a 39% ORR and 32% 3-year progression-free survival rate; rechallenge efficacy was limited.

9503 Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: Primary phase III results from RELATIVITY-047 (CA224-047). EJ Lipson, HA-H Tawbi, D Schadendorf, et al

Take-Home Message Take-Home Message

This study evaluated whether a fixed-dose combination treatment targeting two potentially synergistic immune checkpoint pathways (LAG-3 and PD-1 by relatlimab and nivolumab, respectively) would provide a better benefit–risk profile than monotherapy. The relatlimab plus nivolumab group had significantly longer progression-free survival (PFS; 10.1 months) than the nivolumab group (4.6 months). However, it also had a higher rate of grade 3–4 treatment-related adverse events (18.9% vs 9.7%).

Compared with nivolumab alone, the relatlimab plus nivolumab fixed-dose combination had a significant PFS benefit, indicating that dual inhibition might be a promising strategy. The therapy was also well-tolerated, and the treatment-related adverse events were manageable.

9504 Lenvatinib (len) plus pembrolizumab (pembro) for patients (pts) with advanced melanoma and confirmed progression on a PD-1 or PD-L1 inhibitor: Updated findings of LEAP-004. AM Arance, L de la Cruz-Merino, TM Petrella, et al

Take-Home Message

This update of the LEAP-004 phase II trial reports the effects of lenvatinib (len; kinase inhibitor) plus pembro (PD-1 inhibitor) combination therapy in patients with unresectable stage III/IV melanoma with confirmed progressive disease on a PD-L1 inhibitor with or without anti–CTLA-4 or other treatment. Within 12 weeks of completion of PD-L1 inhibitor therapy, patients received len 20 mg/day plus ≤35 doses of pembro 200 mg IV every three weeks until progressive disease or unacceptable toxicity. At 12 months, PFS was 17.8% and OS was 54.5% for len plus pembro treatment. Most (45.6%) treatment-associated adverse events were grade 3–4, with 7.8% leading to len and/or pembro discontinuation and 56.3% leading to len dose reduction.

Len plus pembro combination treatment continues to be safe and effective in advanced-stage melanoma patients, even in patients with resistance to anti–PD-L1 therapy. The study provided further evidence that this combination therapy may have clinical benefit in this patient population.

9505 Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy. J Larkin, A Sarnaik, JA Chesney, et al

Take-Home Message

As reported in this C-144-01 phase II study update, a single infusion of lifileucel (LN-144; an adoptive tumor-infiltrating lymphocyte cell therapy) was administered to patients with advanced melanoma who progressed on anti–PD-1 therapy and a BRAF inhibitor with or without a MEK inhibitor, if BRAF V600–positive, in combination with 2 days of cyclophosphamide nonmyeloablative lymphodepletion, 5 days of fludarabine, and up to six doses of IL-2. The ORR in patients who received LN-144 was 36.4%. A positive correlation was observed between the duration of response and primary anti–PD-1 resistance and shorter previous anti–PD-1 therapy duration.

This study suggests that one-time TIL treatment may be clinically beneficial in advanced melanoma patients. Further study is warranted to determine whether earlier treatment may provide better outcomes.

9508 Five-year overall survival from the anti-PD1 brain collaboration (ABC Study): Randomized phase 2 study of nivolumab (nivo) or nivo+ipilimumab (ipi) in patients (pts) with melanoma brain metastases (mets). GV Long, V Atkinson, S Lo, et al

Take-Home Message

In this update from the ABC phase II study, patients with asymptomatic melanoma brain metastases who had not received anti–PD-1/PD-L1/PD-L2/CLTA-4 treatment were treated with nivolumab 3 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 12 weeks followed by nivolumab 3 mg/kg every 2 weeks or with nivolumab 3 mg/kg every 2 weeks. Patients with brain metastases who failed local therapy and/or were symptomatic and/or with leptomeningeal disease were also treated with nivolumab (3 mg/kg every 2 weeks). Durable 5-year intracranial progression-free and overall survivals were observed in upfront nivolumab + ipilimumab–treated patients. Combination therapy was also associated with a higher percentage of grade 3/4 treatment-associated adverse events compared with either cohort of patients treated with nivolumab monotherapy.

Nivolumab and nivolumab + ipilimumab continue to demonstrate benefits in patients with melanoma brain metastases, particularly in patients treated upfront with nivolumab + ipilimumab. Additional studies are planned to assess the benefits of nivolumab + ipilimumab with and without stereotactic radiosurgery.

ASCO 2021, abstracten, melanoom