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

Ondine Becquart (1, 2) , Bastien Oriano (3, 4) , Stéphane Dalle (5) , Laurent Mortier (6) , Marie-Thérèse Leccia (7) , Caroline Dutriaux (8) , Sophie Dalac (9) , Henri Montaudié (10) , Julie de Quatrebarbes (11) , Florence Brunet-Possenti (12) , Philippe Saiag (13) , Thierry Lesimple (14) , Marie Beylot-Barry (15, 8) , Francois Aubin (16) , Pierre-Emmanuel Stoebner (1, 17) , Jean-Philippe Arnault (18) , Brigitte Dreno (19) , Raphael Porcher (4) , Celeste Lebbe (3) , Bernard Guillot (2, 20)

1 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
2 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
3 AP-HP - Hopital Saint-Louis [AP-HP]
4 Hôpital Hôtel-Dieu [Paris]
5 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
6 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
7 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
8 CHU Bordeaux
9 Service de Dermatologie (CHU de Dijon)
10 CHU Nice - Centre Hospitalier Universitaire de Nice
11 Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois]
12 AP-HP - Hôpital Bichat - Claude Bernard [Paris]
13 Hôpital Ambroise Paré [AP-HP]
14 CRLCC - CRLCC Eugène Marquis
15 Service de dermatologie [Bordeaux]
16 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
17 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
18 CHU Amiens-Picardie
19 Service de dermatologie [Nantes]
20 UM - Université de Montpellier

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.

Mots clés: Elderly people; Melanoma; Side effects; Targeted therapy

Domaines: Cancer

Ondine Becquart, Bastien Oriano, Stéphane Dalle, Laurent Mortier, Marie-Thérèse Leccia, et al.. Tolerance and Effectiveness of Targeted Therapies in Aged Patients with Metastatic Melanoma. Cancers, 2021, 13 (12), pp.3042. ⟨10.3390/cancers13123042⟩. ⟨hal-03633708⟩