ArticleJournal for immunotherapy of cancer2022
Efficacy and safety of anti-PD1 monotherapy or in combination with ipilimumab after BRAF/MEK inhibitors in patients with BRAF mutant metastatic melanoma.
Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- The role of triple therapy and therapy sequence in treatment of BRAF-mutant metastatic melanoma. Response to overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study.Journal of translational medicine · 2023Trial
- Safety and efficacy of immune checkpoint inhibitors in patients with melanoma and pre-existing autoimmune conditions: a systematic review and meta-analysis.Immuno-oncology technology · 2026Review
- Polymer-based chemo-immunotherapy: Combining immunogenic cell death induction and PD-L1 blockade enhances antitumor immunity in melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2025Article
- BRAF/MEK inhibition induces cell state transitions boosting immune checkpoint sensitivity in BRAFCell reports. Medicine · 2025Article
- Delayed and Concurrent Stereotactic Radiosurgery in Immunotherapy-Naïve Melanoma Brain Metastases.Cancers · 2024Review
- Construction of a tumor mutational burden-derived LncRNA prognostic computational framework associated with therapy sensitivity in skin cutaneous melanoma.Journal of translational medicine · 2024Article
- Construction of a tumor mutational burden-derived LncRNA prognostic computational framework associated with therapy sensitivity in skin cutaneous melanoma.Journal of translational medicine · 2024Article
- Effective control of postoperative recurrence of pregnancy-related gastric cancer using anti-PD-1 as a monotherapy: a case report.Frontiers in oncology · 2024Article
- Sequencing Targeted and Immune Therapy in BRAF-Mutant Melanoma: Lessons Learned.Current oncology reports · 2023Review
- Brain metastases and lung cancer: molecular biology, natural history, prediction of response and efficacy of immunotherapy.Frontiers in immunology · 2023Review
- Review
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Authors and funding
17 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 <10 days between BRAF/MEKi and PD1±IPI, and those with stage III/M1A/M1B melanoma. The combination of ECOG PS=0 and absence of liver metastases identified patients 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.