RESUMO
Background More than half of melanoma patients taking first-line anti-PD-1 therapy either express transient or no response at all. The efficacy and safety of secondary treatments for these patients are still not well established. Here, we evaluate the efficacy and safety of different melanoma FDA-approved ICI modalities used in post-anti-PD-1 refractory settings. Materials and methods We searched the PubMed database and the ASCO meetings library for studies on advanced melanoma patients with cancer progression on anti-PD-1 therapy and were then treated with ipilimumab, nivolumab/ipilimumab combination, or retreated with anti-PD-1. Primary and secondary endpoints were efficacy and toxicity, respectively. Pooled estimates for each treatment group were obtained using a random or fixed effects model according to detected heterogeneity. Results Fourteen studies, of which 10 on ipilimumab, 2 on anti-PD-1 treatment, and 6 on combination therapies, were included, involving a total of 1460 patients. Twelve studies reported objective response rates (ORRs) and nine of them reported immune-related adverse events (irAEs). As for ORR, patients experienced a response that was inferior compared to the same therapy in treatment -naïve patients, with combination therapy having the best ORR of a pooled 23.08% (95% CI: 16.75% to 30.03%), followed by ipilimumab with a pooled ORR of 8.19% (95% CI: 5.78% to 10.92%). Survival data were also inferior in the ipilimumab cohort (mOS: 5.1 to 7.4 months) compared to ipilimumab in anti-PD-1 naive patients. As for grade 3/4 irAE occurrence, the ipilimumab cohort showed an estimate of 43.77% (95% CI 22.55% to 66.19%) (AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Ipilimumab/uso terapêutico , Nivolumabe/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica , Progressão da Doença , Ipilimumab/efeitos adversos , Melanoma/mortalidade , Nivolumabe/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidadeRESUMO
BACKGROUND: More than half of melanoma patients taking first-line anti-PD-1 therapy either express transient or no response at all. The efficacy and safety of secondary treatments for these patients are still not well established. Here, we evaluate the efficacy and safety of different melanoma FDA-approved ICI modalities used in post-anti-PD-1 refractory settings. MATERIALS AND METHODS: We searched the PubMed database and the ASCO meetings library for studies on advanced melanoma patients with cancer progression on anti-PD-1 therapy and were then treated with ipilimumab, nivolumab/ipilimumab combination, or retreated with anti-PD-1. Primary and secondary endpoints were efficacy and toxicity, respectively. Pooled estimates for each treatment group were obtained using a random or fixed effects model according to detected heterogeneity. RESULTS: Fourteen studies, of which 10 on ipilimumab, 2 on anti-PD-1 treatment, and 6 on combination therapies, were included, involving a total of 1460 patients. Twelve studies reported objective response rates (ORRs) and nine of them reported immune-related adverse events (irAEs). As for ORR, patients experienced a response that was inferior compared to the same therapy in treatment -naïve patients, with combination therapy having the best ORR of a pooled 23.08% (95% CI: 16.75% to 30.03%), followed by ipilimumab with a pooled ORR of 8.19% (95% CI: 5.78% to 10.92%). Survival data were also inferior in the ipilimumab cohort (mOS: 5.1 to 7.4 months) compared to ipilimumab in anti-PD-1 naive patients. As for grade 3/4 irAE occurrence, the ipilimumab cohort showed an estimate of 43.77% (95% CI 22.55% to 66.19%). CONCLUSION: Our findings provide the best current evidence that patients who progress on anti-PD-1 can still respond to different ICI modalities (ipilimumab with or without nivolumab, and retreatment or continuation beyond progression with anti-PD-1) with tolerable grade 3/4 irAEs. However, more prospective clinical trials are needed to confirm these results.
