RESUMO
BACKGROUND: Guidelines such as the National Comprehensive Cancer Network recommend mycophenolate mofetil (MMF) for the treatment of severe steroid-refractory immune-related hepatotoxicity. Mycophenolic acid (MPA) is an active form of MMF that suppresses T- and B-lymphocyte proliferation and immune-related adverse events caused by immune checkpoint inhibitors. MPA has a narrow therapeutic range (37-70 µg·h/mL) and overexposure increases the risk of leukopenia in transplantation. However, the optimal use of MMF in oncology has not yet been established; thus, monitoring plasma MPA concentrations is necessary to avoid excessive immunosuppression in oncology practice. CASE PRESENTATION: We evaluated plasma MPA concentration in a 75-year-old man with immune-related hepatotoxicity following nivolumab and ipilimumab combination therapy for malignant melanoma. The patient developed severe hepatotoxicity after immunotherapy, and immunosuppressant therapy with corticosteroids was initiated. The patient then developed steroid-refractory immune-related hepatotoxicity; therefore, MMF (1,000 mg twice daily) was co-administered. Seven days after the administration of MMF, the plasma MPA concentration was measured using an enzyme multiplied immunoassay technique. The area under the plasma concentration-time curve for MPA from 0 to 12 h was 41.0 µg·h/mL, and the same dose of MMF was continued. Grade 2 lymphocytopenia, which could be attributed to MMF, was observed during the administration period. Unfortunately, the patient was infected with SARS-CoV-2 and died from respiratory failure. CONCLUSION: Our patient did not exceed the upper limit of MPA levels as an index of the onset of side effects of kidney transplantation and achieved rapid improvement in liver function. Prompt initiation of MMF after assessment of the steroid effect leads to adequate MPA exposure. Therapeutic drug monitoring should be considered when MMF is administered, to avoid overexposure.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Ipilimumab , Melanoma , Ácido Micofenólico , Nivolumabe , Humanos , Masculino , Nivolumabe/efeitos adversos , Nivolumabe/administração & dosagem , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ipilimumab/efeitos adversos , Ipilimumab/administração & dosagem , Idoso , Melanoma/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Imunossupressores/efeitos adversos , Imunossupressores/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem , Monitoramento de Medicamentos/métodosRESUMO
BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nivolumabe , Compostos de Platina , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Compostos de Platina/administração & dosagem , Compostos de Platina/efeitos adversos , Compostos de Platina/uso terapêutico , Análise de Sobrevida , Terapia CombinadaRESUMO
Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) often requires postoperative chemoradiation with high risk of toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining nivolumab (N), a PD-1-inhibitor and ipilimumab (I), a CTLA4- inhibitor, may improve DFS due to antitumor effects of immunotherapy. The IMSTAR-HN study compares neoadjuvant N and N ± I 6 months after adjuvant therapy versus standard therapy as first-line treatment for LA-HNSCC. Eligible patients have treatment-naive LA-HNSCC, Eastern cooperative oncology group performance score (PS) ≤1 and no distant metastasis. 276 patients will be randomized into two arms. Primary endpoint is DFS and secondary endpoint includes locoregional control (LRC) and overall survival (OS). This study is one of the first in HNSCCs implementing immunotherapy in first-line treatment in a curative setting. Clinical Trial Registration: NCT03700905 (ClinicalTrials.gov).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias de Cabeça e Pescoço/terapia , Inibidores de Checkpoint Imunológico/administração & dosagem , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/metabolismo , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Mitomicina/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Estudos Prospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidadeRESUMO
BACKGROUND: Immune checkpoint inhibitors (ICIs) have produced significant survival benefit across many tumor types. However, immune-related adverse events are common including autoimmune responses against different endocrine organs. Here, a case of ICI-mediated hypoparathyroidism focusing on long-term follow-up and insights into its etiology is presented. CASE AND METHODS: A 73-year-old man developed severe symptomatic hypocalcemia after the initiation of ipilimumab and nivolumab for the treatment of metastatic melanoma. Hypoparathyroidism was diagnosed with undetectable intact parathyroid hormone (PTH). Immunoprecipitation assays, ELISAs, and cell-based functional assays were used to test the patient for antibodies against the calcium-sensing receptor (CaSR). NACHT leucine-rich repeat protein 5 (NALP5) and cytokine antibodies were measured in radioligand binding assays and ELISAs, respectively. RESULTS: The patient's symptoms improved with aggressive calcium and vitamin D supplementation. At 3 years and 3 months since the diagnosis of hypoparathyroidism, PTH was still inappropriately low at 7.6 pg/mL, and attempted discontinuation of calcium and calcitriol resulted in recurrent symptomatic hypocalcemia. Analysis for an autoimmune etiology of the patient's hypoparathyroidism indicated that CaSR antibodies were negative before treatment and detected at multiple time points afterwards, and corresponded to the patient's clinical course of hypoparathyroidism. CaSR antibodies purified from the patient's serum activated the human CaSR. The patient was seronegative for NALP5 and cytokine antibodies, indicating that their hypoparathyroidism was not a manifestation of autoimmune polyendocrine syndrome type 1. CONCLUSION: The etiology of hypocalcemia is likely autoimmune hypoparathyroidism caused by the development of CaSR-activating antibodies that might prevent PTH release from the parathyroid.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Autoanticorpos/imunologia , Hipocalcemia/patologia , Hipoparatireoidismo/patologia , Melanoma/tratamento farmacológico , Receptores de Detecção de Cálcio/imunologia , Idoso , Seguimentos , Humanos , Hipocalcemia/etiologia , Hipoparatireoidismo/induzido quimicamente , Hipoparatireoidismo/imunologia , Ipilimumab/administração & dosagem , Masculino , Melanoma/imunologia , Melanoma/patologia , Nivolumabe/administração & dosagem , PrognósticoRESUMO
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers. After many years of stagnation, there are now several systemic treatments available for patients with HCC. AIM: To analyse the feasibility and efficacy of sequential systemic treatments in patients with HCC in clinical practice. METHODS: In this multicentre study, patients who were treated with novel systemic therapies for HCC between 2014 and 2019 at two referral centres, Hannover Medical School, Germany, and Medical University of Vienna, Austria, were included. RESULTS: Overall, 85 patients were included of which 76 patients (89.4%) received more than one and a maximum of five systemic treatment lines. The most common therapy sequence was sorafenib (n = 72; 84.7%) followed by regorafenib (n = 37; 48.7%), whereas 11 patients were initially treated with lenvatinib (12.9%). Other second-line treatments included pembrolizumab, nivolumab, cabozantinib and ramucirumab. Hepatic function deteriorated during sequential systemic treatment in 48.6% of the patients as defined by an increase in at least one Child-Pugh point. Median overall survival (mOS) from the start of first systemic treatment was 35 months for patients with sequential systemic treatment compared to 9 months for patients with one systemic treatment line (P < 0.001). Patients previously treated with surgical/locoregional therapies had a longer mOS compared to patients with initial systemic treatment (66 vs 25 months; P = 0.020). CONCLUSIONS: Sequential systemic treatment is feasible and effective in selected patients with HCC in clinical practice. Our study underlines the critical importance of well-preserved liver function for successful administration of sequential systemic therapy.
Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Anilidas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Humanos , Masculino , Nivolumabe/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Quinolinas/administração & dosagem , Sorafenibe/administração & dosagem , RamucirumabRESUMO
AIM: To investigate potential association between administration of corticosteroids, antibiotics, probiotics, proton pump inhibitors, non-steroidal anti-inflammatory drugs (NSAID), statins and metformin and outcome in patients with non-small cell lung cancer (NSCLC) treated with nivolumab. PATIENTS AND METHODS: A total of 224 patients with advanced NSCLC treated at nine comprehensive cancer centers were analyzed in this national retrospective study. Survival statistics were evaluated using Kaplan-Meier method and Cox analysis. RESULTS: Only corticosteroid use had a significant negative effect on the objective response rate. In the univariate analysis, there was no significant effect of the studied concomitant medications on the efficacy of nivolumab. In a subsequent multifactorial analysis, a possible positive effect of the concomitant use of NSAID at the initiation of nivolumab treatment was revealed. CONCLUSION: The results of the present retrospective exploratory analysis underscore the importance of knowing the exact type of concomitant medication, the route of administration, the dose of medication, and the region of the ongoing study. The present data indicated a significantly higher rate of progression in patients treated with corticosteroids and the possible positive effect of NSAID use at the initiation of nivolumab treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/métodos , Corticosteroides/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Probióticos/administração & dosagem , Modelos de Riscos Proporcionais , Inibidores da Bomba de Prótons/administração & dosagem , Estudos RetrospectivosRESUMO
INTRODUCTION: In the first-line (1L) setting, pazopanib (PAZ) has been recommended by the National Comprehensive Cancer Network for the treatment of advanced renal cell carcinoma (aRCC). In 2018, immuno-oncology (IO) therapy became a commonly used 1L treatment option for aRCC. We report the real-world clinical outcomes of PAZ after IO therapy for patients with aRCC. MATERIALS AND METHODS: We performed a longitudinal, retrospective medical record review study. The included patients were aged ≥ 18 years, had initiated second-line and/or beyond PAZ after IO therapy for clear cell aRCC on or before October 2017, and had complete medical records available from the diagnosis of aRCC to the discontinuation of PAZ, death, or the medical record extraction date (May 2018), whichever occurred first. The primary outcome variable was the PAZ duration of therapy. The secondary outcomes were progression-free survival and overall survival since PAZ initiation, the reasons for PAZ discontinuation, and the occurrence of adverse events (AEs). RESULTS: A total of 258 eligible patients had initiated IO therapies before PAZ as follows: nivolumab (68%), nivolumab plus ipilimumab (14%), pembrolizumab (12%), and ipilimumab (3%). Overall, the median PAZ duration of therapy was 13.4 months (95% confidence interval [CI], 10.1-16.0 months). The median progression-free survival with PAZ after IO therapy was 13.5 months (95% CI, 11.8 months to not reached). The estimated overall survival rate of PAZ after IO therapy at 6 and 12 months was 93% and 89%, respectively. A total of 109 patients (42%) had reported an AE. The most frequently reported AEs were fatigue (29%) and diarrhea (14%). No additional safety signal of hepatotoxicity was observed (increased aspartate aminotransferase, 5%; increased alanine transaminase, 6%). CONCLUSIONS: In the present real-world study, second-line and/or beyond PAZ after previous IO therapy was well-tolerated and effective for patients with aRCC.
Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Fadiga/induzido quimicamente , Fadiga/epidemiologia , Feminino , Humanos , Indazóis , Ipilimumab/administração & dosagem , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/administração & dosagem , Intervalo Livre de Progressão , Pirimidinas/efeitos adversos , Estudos Retrospectivos , Sulfonamidas/efeitos adversos , Fatores de TempoRESUMO
BACKGROUND: Although a myriad of novel treatments entered the treatment paradigm for advanced melanoma, there is lack of head-to-head evidence. We conducted a network meta-analysis (NMA) to estimate each treatment's relative effectiveness and safety. METHODS: A systematic literature review (SLR) was conducted in Embase, MEDLINE and Cochrane to identify all phase III randomised controlled trials (RCTs) with a time frame from January 1, 2010 to March 11, 2019. We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS). Evidence was synthesised using a Bayesian fixed-effect NMA. Reference treatment was dacarbazine. In accordance with RCTs, dacarbazine was pooled with temozolomide, paclitaxel and paclitaxel plus carboplatin. To increase homogeneity of the study populations, RCTs were only included if patients were not previously treated with novel treatments. RESULTS: The SLR identified 28 phase III RCTs involving 14,376 patients. Nineteen and seventeen treatments were included in the effectiveness and safety NMA, respectively. For PFS, dabrafenib plus trametinib (hazard ratio [HR] PFS: 0.21) and vemurafenib plus cobimetinib (HR PFS: 0.22) were identified as most favourable treatments. Both had, however, less favourable safety profiles. Five other treatments closely followed (dabrafenib [HR PFS: 0.30], nivolumab plus ipilimumab [HR PFS: 0.34], vemurafenib [HR PFS: 0.38], nivolumab [HR PFS: 0.42] and pembrolizumab [HR PFS: 0.46]). In contrast, for OS, nivolumab plus ipilimumab (HR OS: 0.39), nivolumab (HR OS: 0.46) and pembrolizumab (HR OS: 0.50) were more favourable than dabrafenib plus trametinib (HR OS: 0.55) and vemurafenib plus cobimetinib (HR OS: 0.57). CONCLUSIONS: Our NMA identified the most effective treatment options for advanced melanoma and provided valuable insights into each novel treatment's relative effectiveness and safety. This information may facilitate evidence-based decision-making and may support the optimisation of treatment and outcomes in everyday clinical practice.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Azetidinas/administração & dosagem , Azetidinas/uso terapêutico , Benzimidazóis/administração & dosagem , Benzimidazóis/uso terapêutico , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Dacarbazina/administração & dosagem , Dacarbazina/uso terapêutico , Humanos , Hidrazinas/administração & dosagem , Hidrazinas/uso terapêutico , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Ipilimumab/administração & dosagem , Ipilimumab/uso terapêutico , Lenalidomida/administração & dosagem , Lenalidomida/uso terapêutico , Melanoma/imunologia , Melanoma/patologia , Metanálise em Rede , Compostos de Nitrosoureia/administração & dosagem , Compostos de Nitrosoureia/uso terapêutico , Nivolumabe/administração & dosagem , Nivolumabe/uso terapêutico , Compostos Organofosforados/administração & dosagem , Compostos Organofosforados/uso terapêutico , Oximas/administração & dosagem , Oximas/uso terapêutico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Piridonas/administração & dosagem , Piridonas/uso terapêutico , Pirimidinonas/administração & dosagem , Pirimidinonas/uso terapêutico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Sorafenibe/administração & dosagem , Sorafenibe/uso terapêutico , Taxa de Sobrevida , Temozolomida/administração & dosagem , Temozolomida/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. METHODS: The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. DISCUSSION: The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. TRIAL REGISTRATION: PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). TRIAL STATUS: At the time of submission, PRISM is open to recruitment and data collection is ongoing.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Ipilimumab/administração & dosagem , Nivolumabe/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Ipilimumab/efeitos adversos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nivolumabe/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Qualidade de Vida , Resultado do TratamentoAssuntos
Insuficiência Adrenal/induzido quimicamente , Micose Fungoide/patologia , Micose Fungoide/terapia , Psoríase/etiologia , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Brentuximab Vedotin/administração & dosagem , Brentuximab Vedotin/efeitos adversos , Brentuximab Vedotin/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Micose Fungoide/radioterapia , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Fototerapia/métodos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Psoríase/tratamento farmacológico , Psoríase/patologia , Resultado do TratamentoRESUMO
OBJECTIVES: A wide range of objective response rates (ORRs: 0-53%) among available treatments in patients with R/M HNSCC with progression on or after platinum-based chemotherapy (PBT) renders treatment selection a challenge. This systematic literature review (SLR) was intended to aid clinical decision-making by classifying historical studies to accurately characterize the response in second-line (progression on/after platinum-based therapy), and third-line (progression on/after platinum and cetuximab/other drug) settings. METHODS: SLR was performed to characterize the ORR, duration of response (DOR), progression-free survival (PFS) and overall survival (OS) with therapies recommended by the National Comprehensive Cancer Network (NCCN) guidelines. Clinical trials published in English between January 1, 1985, and September 30, 2016 were identified by searching the PubMed (Medline), Cochrane, and Embase databases. RESULTS: The SLR identified 34 key studies in second-line R/M HNSCC patients, and one of these included a third-line patient cohort. However, several studies did not enrol a strictly second-line population. Response in a true second-line setting was elucidated by categorizing the studies using a novel framework defined according to the extent to which enrolled patients were second-line. Only seven studies were strictly second-line, with an estimated pooled ORR of 4% (95% CIâ¯=â¯2-8%; Nâ¯=â¯414) for methotrexate and 11% (95% CIâ¯=â¯7-15%; Nâ¯=â¯235) for cetuximab, and a reported ORR of 14% (Nâ¯=â¯78) from a single study of paclitaxel. The median DOR was limited with cetuximab (â¼4 months) and paclitaxel (â¼7 months), and not reported for methotrexate. Median PFS or time to progression (TTP) ranged from 1.7 to 3.5â¯months, and median OS from 4.3 to 6.7â¯months. The ORR in the only third-line study was 0% (95% CIâ¯=â¯0-7; Nâ¯=â¯53) for the platinumâ¯+â¯cetuximab combination. CONCLUSION: These findings emphasize the historically bleak prognoses in patients with R/M HNSCC following PBT progression. Anti-PD-1 therapies, namely pembrolizumab and nivolumab, represent novel treatment options that may improve clinical outcomes.