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Identifying High-Risk Tumors within AJCC Stage IB–III Melanomas Using a Seven-Marker Immunohistochemical Signature

Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma

CHU de Montpellier, Service de Dermatologie, 34295 Montpellier, France
Hôpital St Louis, APHP, Service de Dermatologie, 75010 Paris, France
Hôpital Hôtel-Dieu, APHP, Centre d’Épidémiologie Clinique, 75010 Paris, France
Service de Dermatologie, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, 69002 Lyon, France
CHRU Lille, Service de Dermatologie, 59000 Lille, France
CHU Grenoble, Service de Dermatologie, 38000 Grenoble, France
CHU Bordeaux Saint-André, Service de Dermatologie, 33000 Bordeaux, France
CHU Dijon, Service de Dermatologie, 21000 Dijon, France
CHU Nice, Service de Dermatologie, 06000 Nice, France
CH d’Annecy-Genevois, Service de Dermatologie, 74370 Annecy, France
Hôpital Bichat, APHP, Paris, Service de Dermatologie, 75018 Paris, France
Hôpital Ambroise Pare, APHP, Service de Dermatologie, 92100 Boulogne-Billancourt, France
CLCC Eugène Marquis, Service d’Oncologie, 35000 Rennes, France
CHU Jean Mermoz, Service de Dermatologie, 25000 Besançon, France
CHU Nîmes, Service de Dermatologie, 30000 Nîmes, France
CHU Amiens, Service de Dermatologie, 80000 Amiens, France
CHU Nantes, Service de Dermatologie, 44000 Nantes, France
Departement de Dermatologie, University of Montpellier, 34000 Montpellier, France
Author to whom correspondence should be addressed.
Academic Editor: Brian Gabrielli
Cancers 2021, 13(12), 3042;
Received: 18 May 2021 / Revised: 11 June 2021 / Accepted: 14 June 2021 / Published: 18 June 2021
(This article belongs to the Special Issue Targeted Therapies and Immunotherapies in Metastatic Melanoma)
A majority of melanoma occurs in people over 65 years. BRAF and MEK inhibitors are standard of care for BRAF mutated metastatic melanoma. The aim of the study was to explore tolerability of targeted therapy in a cohort of patients extracted from a biobank. Patients treated by BRAF and/or MEK inhibitors were included in two groups (<65 or >65 years) and analyzed for tolerance and efficacy. The cohort included 353 patients: 231 < 65 years and 122 > 65. A total of 80% had at least one adverse effect mainly skin, general, and gastrointestinal disorders. No statistical difference was observed for severe adverse events, adverse events grades, dose modifications, and interruptions in the two groups. Median overall survival was 20.3 and 16.3 months, respectively. This study shows that tolerance of targeted therapy is as good in older patients as in younger with a similar efficacy. There is no argument against using these treatments in elderly people.
Purpose: Melanoma’s incidence is increasing, and elderly people could be significantly impacted since the majority occurs in people over 65 years of age. Combined BRAF and MEK targeted therapies (TT) are current standard regimen for BRAF mutated metastatic melanoma (MM). Except for subgroups of pivotal trials, little data are available for TT in this population. Materials and Methods: Outcomes were explored in real life patients from MelBase, a French multicentric biobank dedicated to the prospective follow-up of unresectable stage III or IV melanoma. Patients treated by BRAF TT and/or MEK TT combined or not, were included from 2013 to 2017 in 2 groups: group 1 ≤ 65-year-old (yo), group 2 > 65 yo, analyzed for tolerance and efficacy. Results: 353 patients were included: 231 in group 1, 122 in group 2. Median follow-up was 12 months (M). Median time of treatment was 6.9 M. A total of 80% had at least one Adverse Effect (AE). Most frequent AE (all grades) were mainly skin and subcutaneous, general, and gastrointestinal disorders. A total of 31% of AE were grade 3–4: 28% in group 1 and 39% in group 2 (p = 0.05). No differences were observed in all AE grades proportion, dose modifications, interruptions, and discontinuations. For each group, median overall survival was 20.3 M (CI 95%: 15.5–27.9) and 16.3 M (CI: 14.5–26.9), respectively (p = 0.8). Median progression free survival was 7.8 M (6.4–9.9) and 7.7 M (CI: 5.8–11.3) (p = 0.4). Objective response rate was 59% and 50% (p = 0.6). Conclusion: This study on a large multicentric cohort is the first to assess that TT is well tolerated in elderly BRAF-mutated patients such as in patients younger than 65. Efficacy was similar between groups with outcomes reaching those from pivotal studies. There is thus no argument against using TT in elderly people, although an onco-geriatric opinion is welcome for the most vulnerable. View Full-Text
Keywords: melanoma; targeted therapy; elderly people; side effects melanoma; targeted therapy; elderly people; side effects
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MDPI and ACS Style

Becquart, O.; Oriano, B.; Dalle, S.; Mortier, L.; Leccia, M.T.; Dutriaux, C.; Dalac, S.; Montaudié, H.; De Quatrebarbes, J.; Brunet-Possenti, F.; Saiag, P.; Lesimple, T.; Beylot-Barry, M.; Aubin, F.; Stoebner, P.-E.; Arnault, J.-P.; Dreno, B.; Porcher, R.; Lebbe, C.; Guillot, B. Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma. Cancers 2021, 13, 3042.

AMA Style

Becquart O, Oriano B, Dalle S, Mortier L, Leccia MT, Dutriaux C, Dalac S, Montaudié H, De Quatrebarbes J, Brunet-Possenti F, Saiag P, Lesimple T, Beylot-Barry M, Aubin F, Stoebner P-E, Arnault J-P, Dreno B, Porcher R, Lebbe C, Guillot B. Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma. Cancers. 2021; 13(12):3042.

Chicago/Turabian Style

Becquart, Ondine, Bastien Oriano, Stéphane Dalle, Laurent Mortier, Marie T. Leccia, Caroline Dutriaux, Sophie Dalac, Henri Montaudié, Julie De Quatrebarbes, Florence Brunet-Possenti, Philippe Saiag, Thierry Lesimple, Marie Beylot-Barry, Francois Aubin, Pierre-Emmanuel Stoebner, Jean-Philippe Arnault, Brigitte Dreno, Raphael Porcher, Celeste Lebbe, and Bernard Guillot. 2021. "Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma" Cancers 13, no. 12: 3042.

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