Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma
Abstract Background Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAF...
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BMC
2018-07-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-018-4618-9 |
| _version_ | 1811288990973689856 |
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| author | M. Amini-Adle N. Khanafer M. Le-Bouar G. Duru S. Dalle L. Thomas |
| author_facet | M. Amini-Adle N. Khanafer M. Le-Bouar G. Duru S. Dalle L. Thomas |
| author_sort | M. Amini-Adle |
| collection | DOAJ |
| description | Abstract Background Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. Methods This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). Results Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3–3.9; p = 0.003) and 2.5 (95%CI:1.3–4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). Discussion This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy. |
| first_indexed | 2024-04-13T03:47:00Z |
| format | Article |
| id | doaj.art-7bb07e4322cc428e81d8bde64ceb61b1 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T03:47:00Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-7bb07e4322cc428e81d8bde64ceb61b12022-12-22T03:03:59ZengBMCBMC Cancer1471-24072018-07-011811710.1186/s12885-018-4618-9Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanomaM. Amini-Adle0N. Khanafer1M. Le-Bouar2G. Duru3S. Dalle4L. Thomas5Department of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon 1 UniversityUnit of Epidemiology and Infection Control Unit, Hôpital Edouard Herriot, Hospices Civils de Lyon, Laboratory of Emergent Pathogens, CIRI, Claude Bernard Lyon 1 UniversityDepartment of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon 1 UniversityDepartment of Biostatistics, Claude Bernard Lyon 1 UniversityDepartment of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon 1 UniversityDepartment of Dermatology, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon 1 UniversityAbstract Background Anti-PD-1 and BRAF-inhibitors (BRAFi) have been approved as first-line treatments in advanced melanoma. To date, no prospective data are available to give the best sequence of treatment. The objective of this study was to evaluate in real-life the efficacy of anti-PD-1 after BRAFi, ipilimumab, or chemotherapy failure. Methods This was a single institution cohort analysis in patients treated with anti-PD-1 right after BRAFi, ipilimumab, or chemotherapy failure. Melanoma evolution after anti-PD-1 initiation was analyzed in BRAF-mutated and BRAF wild-type patients. The efficacy of treatment was evaluated by Objective Response Rate (ORR), Disease Control Rate (DCR), Progression-Free Survival (PFS), and Overall Survival (OS). Results Seventy-four patients were included: 33 wild-type and 41 BRAF-mutated melanoma. ORR to anti-PD-1 was significantly lower in BRAF-mutated patients (12.2% vs. 45.5%, p = 0.002). After anti-PD-1 initiation, the median PFS and OS was significantly shorter in the BRAF mutated group (2 vs. 5 months and 7 vs. 20 months, p = 0.001). The hazard ratio for disease progression was of 2.3 (95%CI:1.3–3.9; p = 0.003) and 2.5 (95%CI:1.3–4.5; p = 0.005) for death. Thirty-nine percent of BRAF-mutated-patients died within 3 months after anti-PD-1 initiation. Rapid death (≤3 months) was significantly higher in BRAF-mutated patients (55.2% vs. 20.0%, p = 0.014). Discussion This is the largest series of unselected patients treated in real-life with anti-PD-1 as second-or-higher line of treatment. Anti-PD-1 was less effective in BRAF-mutated cases as a majority of patients presented aggressive tumor evolution after BRAFi discontinuation. These data are consistent with previous studies suggesting a negative impact of BRAFi prior to immunotherapy.http://link.springer.com/article/10.1186/s12885-018-4618-9Anti PD-1BRAF inhibitorImmunotherapyMelanomaTreatment sequence |
| spellingShingle | M. Amini-Adle N. Khanafer M. Le-Bouar G. Duru S. Dalle L. Thomas Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma BMC Cancer Anti PD-1 BRAF inhibitor Immunotherapy Melanoma Treatment sequence |
| title | Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma |
| title_full | Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma |
| title_fullStr | Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma |
| title_full_unstemmed | Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma |
| title_short | Ineffective anti PD-1 therapy after BRAF inhibitor failure in advanced melanoma |
| title_sort | ineffective anti pd 1 therapy after braf inhibitor failure in advanced melanoma |
| topic | Anti PD-1 BRAF inhibitor Immunotherapy Melanoma Treatment sequence |
| url | http://link.springer.com/article/10.1186/s12885-018-4618-9 |
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