Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF/MEK inhibitors in patients with BRAF mutant metastatic melanoma
| Autor: | Ines Pires da Silva, Danny Zakria, Tasnia Ahmed, Claudia Trojanello, Florentia Dimitriou, Clara Allayous, Camille Gerard, Lisa Zimmer, Serigne Lo, Olivier Michielin, Celeste Lebbe, Johanna Mangana, Paolo Antonio Ascierto, Douglas B Johnson, Matteo Carlino, Alexander Menzies, Georgina Long |
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| Přispěvatelé: | University of Zurich, Long, Georgina |
| Rok vydání: | 2022 |
| Předmět: |
Proto-Oncogene Proteins B-raf
Cancer Research Skin Neoplasms Immunology Medizin 610 Medicine & health Humans Immunology and Allergy 1306 Cancer Research Melanoma Protein Kinase Inhibitors Mitogen-Activated Protein Kinase Kinases Pharmacology 2403 Immunology Brain Neoplasms 10177 Dermatology Clinic Neoplasms Second Primary Ipilimumab 3004 Pharmacology Oncology 1313 Molecular Medicine Mutation 2723 Immunology and Allergy Molecular Medicine 2730 Oncology Female |
| Zdroj: | Journal for ImmunoTherapy of Cancer. 10:e004610 |
| ISSN: | 2051-1426 |
| Popis: | BackgroundPatients with V600BRAF mutant metastatic melanoma have higher rates of progression-free survival (PFS) and overall survival (OS) with first-line anti-PD1 (PD1]+anti-CTLA-4 (IPI) versus PD1. Whether this is also true after BRAF/MEKi therapy is unknown. We aimed to determine the efficacy and safety of PD1 versus IPI +PD1 after BRAF/MEK inhibitors (BRAF/MEKi).MethodsPatients with V600BRAF mutant metastatic melanoma treated with BRAF/MEKi who had subsequent PD1 versus IPI+PD1 at eight centers were included. The endpoints were objective response rate (ORR), PFS, OS and safety in each group.ResultsOf 200 patients with V600E (75%) or non-V600E (25%) mutant metastatic melanoma treated with BRAF/MEKi (median time of treatment 7.6 months; treatment cessation due to progressive disease in 77%), 115 (57.5%) had subsequent PD1 and 85 (42.5%) had IPI+PD1. Differences in patient characteristics between PD1 and IPI+PD1 groups included, age (med. 63 vs 54 years), time between BRAF/MEKi and PD1±IPI (16 vs 4 days), Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≥1 (62% vs 44%), AJCC M1C/M1D stage (72% vs 94%) and progressing brain metastases at the start of PD1±IPI (34% vs 57%). Median follow-up from PD1±IPI start was 37.8 months (95% CI, 33.9 to 52.9). ORR was 36%; 34% with PD1 vs 39% with IPI+PD1 (p=0.5713). Median PFS was 3.4 months; 3.4 with PD1 vs 3.6 months with IPI+PD1 (p=0.6951). Median OS was 15.4 months; 14.4 for PD1 vs 20.5 months with IPI+PD1 (p=0.2603). The rate of grade 3 or 4 toxicities was higher with IPI+PD1 (31%) vs PD1 (7%). ORR, PFS and OS were numerically higher with IPI+PD1 vs PD1 across most subgroups except for females, those with 3 years OS (area under the curve, AUC=0.74), while ECOG PS ≥1, progressing brain metastases and presence of bone metastases predicted primary progression (AUC=0.67).ConclusionsIPI+PD1 and PD1 after BRAF/MEKi have similar outcomes despite worse baseline prognostic features in the IPI+PD1 group, however, IPI+PD1 is more toxic. A combination of clinical factors can identify long-term survivors, but less accurately those with primary resistance to immunotherapy after targeted therapy. |
| Databáze: | OpenAIRE |
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