Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase)
BackgroundThe tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1250026/full |
| _version_ | 1827786386598526976 |
|---|---|
| author | David Russo Stéphane Dalle Olivier Dereure Laurent Mortier Sophie Dalac-Rat Caroline Dutriaux Marie-Thérèse Leccia Marie-Thérèse Leccia Delphine Legoupil Henri Montaudié Eve Maubec Julie De Quatrebarbes Jean-Philippe Arnault Florence Granel Brocard Philippe Saïag Brigitte Dreno Clara Allayous Clara Allayous Bastien Oriano Wendy Lefevre Céleste Lebbé Céleste Lebbé Lise Boussemart Lise Boussemart |
| author_facet | David Russo Stéphane Dalle Olivier Dereure Laurent Mortier Sophie Dalac-Rat Caroline Dutriaux Marie-Thérèse Leccia Marie-Thérèse Leccia Delphine Legoupil Henri Montaudié Eve Maubec Julie De Quatrebarbes Jean-Philippe Arnault Florence Granel Brocard Philippe Saïag Brigitte Dreno Clara Allayous Clara Allayous Bastien Oriano Wendy Lefevre Céleste Lebbé Céleste Lebbé Lise Boussemart Lise Boussemart |
| author_sort | David Russo |
| collection | DOAJ |
| description | BackgroundThe tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment.Patients and methodsPatients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS).Results973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients’ characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively).ConclusionOur study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research. |
| first_indexed | 2024-03-11T16:33:43Z |
| format | Article |
| id | doaj.art-f844a1fc7d06416ea3d2882e024c7f02 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-11T16:33:43Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-f844a1fc7d06416ea3d2882e024c7f022023-10-23T21:12:45ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-10-011310.3389/fonc.2023.12500261250026Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase)David Russo0Stéphane Dalle1Olivier Dereure2Laurent Mortier3Sophie Dalac-Rat4Caroline Dutriaux5Marie-Thérèse Leccia6Marie-Thérèse Leccia7Delphine Legoupil8Henri Montaudié9Eve Maubec10Julie De Quatrebarbes11Jean-Philippe Arnault12Florence Granel Brocard13Philippe Saïag14Brigitte Dreno15Clara Allayous16Clara Allayous17Bastien Oriano18Wendy Lefevre19Céleste Lebbé20Céleste Lebbé21Lise Boussemart22Lise Boussemart23Department of Dermatology, Pontchaillou Hospital, CHU de Rennes, Rennes, FranceCancer Research Center of Lyon, Hospices Civils de Lyon, Pierre-Bénite, FranceDepartment of Dermatology, Hôpital Saint-Eloi, CHU de Montpellier, Montpellier, FranceUniversité Lille, Centre Hospitalier Régional Universitaire de Lille, Lille, FranceDermatology Department, CHU Dijon Bourgogne, CHU Le Bocage, Dijon, FranceCentre Hospitalier Universitaire de Bordeaux, Hôpital Saint-André, Bordeaux, FranceDermatology Department, CHU Albert Michalon, Grenoble, FranceInserm, U1209, Université de Grenoble, Grenoble, FranceDermatology Department, CHRU Brest, Brest, France0Dermatology Department, Nice Hospital, Nice, France1Dermatology Department, Avicenne Hospital, AP-HP, Bobigny, France2Dermatology Department, CH d’Annecy, Pringy, France3Dermatology Department, CHU Amiens Picardie, Amiens, France4Dermatology Department, CHU de Nancy, Nancy, France5Dermatology Department, Université de Versailles-Saint Quentin en Yvelines, AP-HP, Boulogne, France6Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France7AP-HP, Dermatology Department, Hôpital Saint-Louis, Paris, France8Université de Paris, AP-HP Saint-Louis Hospital, Dermatology Department, INSERM U976, Paris, France7AP-HP, Dermatology Department, Hôpital Saint-Louis, Paris, France7AP-HP, Dermatology Department, Hôpital Saint-Louis, Paris, France7AP-HP, Dermatology Department, Hôpital Saint-Louis, Paris, France8Université de Paris, AP-HP Saint-Louis Hospital, Dermatology Department, INSERM U976, Paris, France6Nantes Université, Univ Angers, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, UMR 1302, Nantes, France9Dermatology Department, CHU de Nantes, Nantes, FranceBackgroundThe tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment.Patients and methodsPatients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS).Results973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients’ characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively).ConclusionOur study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research.https://www.frontiersin.org/articles/10.3389/fonc.2023.1250026/fullmelanomaimmunotherapysun-exposureacral melanomaUV signature |
| spellingShingle | David Russo Stéphane Dalle Olivier Dereure Laurent Mortier Sophie Dalac-Rat Caroline Dutriaux Marie-Thérèse Leccia Marie-Thérèse Leccia Delphine Legoupil Henri Montaudié Eve Maubec Julie De Quatrebarbes Jean-Philippe Arnault Florence Granel Brocard Philippe Saïag Brigitte Dreno Clara Allayous Clara Allayous Bastien Oriano Wendy Lefevre Céleste Lebbé Céleste Lebbé Lise Boussemart Lise Boussemart Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) Frontiers in Oncology melanoma immunotherapy sun-exposure acral melanoma UV signature |
| title | Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) |
| title_full | Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) |
| title_fullStr | Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) |
| title_full_unstemmed | Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) |
| title_short | Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase) |
| title_sort | differential gradients of immunotherapy vs targeted therapy efficacy according to the sun exposure pattern of the site of occurrence of primary melanoma a multicenter prospective cohort study melbase |
| topic | melanoma immunotherapy sun-exposure acral melanoma UV signature |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1250026/full |
| work_keys_str_mv | AT davidrusso differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT stephanedalle differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT olivierdereure differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT laurentmortier differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT sophiedalacrat differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT carolinedutriaux differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT mariethereseleccia differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT mariethereseleccia differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT delphinelegoupil differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT henrimontaudie differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT evemaubec differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT juliedequatrebarbes differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT jeanphilippearnault differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT florencegranelbrocard differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT philippesaiag differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT brigittedreno differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT claraallayous differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT claraallayous differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT bastienoriano differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT wendylefevre differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT celestelebbe differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT celestelebbe differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT liseboussemart differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase AT liseboussemart differentialgradientsofimmunotherapyvstargetedtherapyefficacyaccordingtothesunexposurepatternofthesiteofoccurrenceofprimarymelanomaamulticenterprospectivecohortstudymelbase |