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BACKGROUND: The benefit of immune checkpoint inhibitors (ICIs) for poor performance status patients with advanced urothelial carcinoma (UC) remains unknown. OBJECTIVE: In the present sub-analysis of the ARON-2 study, we investigated the role of pembrolizumab for advanced UC patients with ECOG (Eastern Cooperative Oncology Group) performance status (ECOG-PS) 2. PATIENTS AND METHODS: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of advanced UC progressing or recurring after platinum-based therapy and treated with pembrolizumab between 1 January 2016 to 1 April 2024 were included. In this sub-analysis we focused on patients with ECOG-PS 2. RESULTS: We included 1,040 patients from the ARON-2 dataset; of these, 167 patients (16%) presented an ECOG-PS 2. The median overall survival (OS) was 14.8 months (95% confidence interval (CI) 12.5-16.1) in the overall study population, 18.2 months (95% CI 15.8-22.2) in patients with ECOG-PS 0-1, and 3.7 months (95% CI 3.2-5.2) in subjects with ECOG-PS 2 (p < 0.001). The median progression-free survival (PFS) in the overall study population was 5.3 months (95% CI 4.3-97.1), 6.2 months (95% CI 5.5-97.1) in patients with ECOG-PS 0-1, and 2.8 months (95% CI 2.1-3.4) in patients with ECOG-PS 2. Among the latter, liver metastases and progressive disease during first-line therapy were significant predictors of OS at both univariate and multivariate analyses. For PFS, univariate and multivariate analyses showed a prognostic role for lung metastases, liver metastases, and progressive disease during first-line therapy. CONCLUSIONS: This large real-world evidence study suggests the effectiveness of second-line pembrolizumab for mUC patients with poor performance status. The presence of liver metastases and progressive disease during first-line therapy is associated with worse clinical outcomes and, thus, should be taken into account when making treatment decisions in clinical practice.
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BACKGROUND: This study aimed to evaluate the utility of RECIST criteria-based objective response rate (ORR) as a potential surrogate endpoint for long-term overall survival (OS) in patients with metastatic urothelial carcinoma who were treated with immune checkpoint inhibitors (ICIs). METHODS: The primary endpoint was overall ORR and OS, duration of treatment (DoR) with ICIs. ORR was analyzed using Fisher's exact test. Median follow-up and OS were estimated by using the Kaplan-Meier method. RESULTS: The median follow-up was 58 (1.15-71) months. Progression developed in 94 (47%) patients during the first 3 months of ICIs therapy. The treatment response to ICIs included complete response (CR), partial response (PR) and stable disease in 10% (n = 20), 23% (n = 46), and 20% (n = 41) of patients, respectively. The responder and nonresponder groups differed in terms of certain baseline characteristics, such as Bellmunt risk factors, and neutrophil-to-lymphocyte ratio (NLR). The 5-year OS rates for patients with CR and PR were 73% and 23%, respectively. The median DoR for CR, PR, and SD were 51.8 months (44.5-59.1), 20.7 months (16.7-24.6), and 8.8 months (5.5-12.1), respectively. Overall, 16(80%) patients with CR and 14(30%) patients with PR had an ongoing response at the time of the analysis. In the univariate analysis, NLR > 3, liver metastases, ECOG PS ≥ 1, and hemoglobin levels < 10 mg/dl, as well as the PR and CR, were all significantly associated with OS. In multivariate analysis, presence of liver metastases (HR 2.3; 95% CI, 1.3-4.2; P < .004) was found to be an independent determinant of short OS, while PR (HR 0.3; 95% CI, 0.15-0.5; P < .001) and CR (HR 0.06; 95% CI, 0.014-0.27; P < .001) were associated with improved OS. CONCLUSIONS: In conclusion, this 5-year analysis of real-world data in the setting of metastatic urothelial cancer indicated a significant correlation between ORR, especially CR, and OS in patients who received ICIs. Therefore, identifying a potential surrogate marker for survival in patients treated with ICIs would represent an important advance in the early identification of patients' response or resistance to ICIs.
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The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33â ±â 0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67-2.20, Pâ =â .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status.
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Neoplasias da Mama , Quinase 4 Dependente de Ciclina , Quinase 6 Dependente de Ciclina , Receptor ErbB-2 , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Estudos Retrospectivos , Pessoa de Meia-Idade , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Idoso , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Adulto , Intervalo Livre de Progressão , Receptores de Estrogênio/metabolismoRESUMO
Background: Low serum sodium affects cancer prognosis, but its impact on immunotherapy is unclear. Objective: Assessing the association of pre- and post-ICI treatment sodium levels with survival. Methods: We retrospectively analyzed patients receiving ICI in January 2012-December 2023, collecting serum sodium levels at treatment initiation and 4 weeks post-ICI, with overall survival (OS) as the primary outcome. Results: Low sodium was observed in 125 and 119 patients pre-and post-treatment respectively. Pre-ICI and post-ICI low sodium correlated with decreased OS [10.6 vs. 22.9 months (p = 0.001) and 11.6 vs. 27.2 months (p = 0.009)]. Multivariate analysis identified pre-ICI low sodium [HR: 1.685; 95% CI: 1.050-2.705; p = 0.031] as an independent risk factor for worse OS. Conclusion: Low baseline serum sodium was an independent risk factor for poor OS in patients treated with ICIs.
This study explored how sodium levels impact cancer patients' outcomes during treatment with immune checkpoint inhibitors (ICIs). We examined sodium levels before and after ICI treatment in patients with cancer. Low sodium levels both before and after treatment were associated with poorer outcomes. Specifically, patients with low sodium levels before treatment had shorter survival times compared to those with normal levels. Similarly, patients with low sodium levels after treatment had shorter survival times compared to those with normal levels. These findings suggest that low baseline sodium levels could indicate poorer outcomes in patients receiving ICIs.
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INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica , Quimiorradioterapia Adjuvante , Cisplatino , Docetaxel , Fluoruracila , Leucovorina , Estadiamento de Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Docetaxel/administração & dosagem , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Idoso , Adulto , Estudos Retrospectivos , Quimiorradioterapia Adjuvante/métodos , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Resultado do TratamentoRESUMO
Recent progress in adjuvant immunotherapy offers hope for improving disease-free survival in high-risk bladder cancer (BC) and renal cell carcinoma (RCC). This review focuses on key trials such as CheckMate 274 and KEYNOTE-564, which show promising results with nivolumab in BC and pembrolizumab in RCC, including a 30% reduction in progression risk. Pembrolizumab also demonstrated overall survival (OS) benefit in RCC. The review also explores the potential of circulating tumor DNA (ctDNA) as a biomarker for better therapy selection and patient stratification. It emphasizes the need for ongoing research to establish survival benefits and suggests integrating biomarkers and risk stratification to optimize adjuvant immunotherapy in BC and RCC.
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OBJECTIVE: To evaluate the efficacy and safety of nivolumab in the second-line (2L) or later-line (LL) treatment of patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) in real-life setting in Türkiye. METHODS: This study was designed as a national, multi-center, retrospective study. The study population was evaluated in two groups for the line of nivolumab therapy: those receiving nivolumab in the 2L (Group 2L) and third-line (3L) or LL (Group 3L/LL). Efficacy was evaluated based on one-year overall survival (OS) and progression-free survival (PFS). Safety was evaluated based on treatment-related adverse events (AEs) and nivolumab discontinuation rate. RESULTS: Of 244 patients, 52.9% were in Group 2L and 47.1% were in Group 3L/LL. Demographic and clinical characteristics did not differ between the groups. In Group 2L and Group 3L/LL, one-year OS and PFS rates were 60.8% and 61.4% (p = 0.592) and 31.2% and 21.3% (p = 0.078), respectively. The objective response rate (ORR) was 34.7% in Group 2L and 27.3% in Group 3L/LL (p = 0.262). The percentage of patients reporting at least one AE in Groups 2L and 3L/LL was 34.9% and 43.5%, respectively (p = 0.169). Fatigue was the most common (16.4%) treatment-related AE in each group. The groups were comparable regarding the AE frequency. Nivolumab was discontinued in 61 patients in Group 2L and 53 patients in Group 3L/LL, with the most common reason being disease progression (57.4% and 66.0%, respectively). CONCLUSION: Nivolumab is safe and effective in the 2L or 3L/LL treatment of locally advanced/metastatic NSCLC and associated with acceptable AEs in real-life setting.
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (around 85% of all lung cancers). Patients with NSCLC are usually diagnosed at advanced or metastatic stages. When cancer cells spread to other areas from where they first formed, it is called metastatic cancer. Surgery may not be a treatment option for such patients. Currently, immunotherapeutic agents are used in the treatment of NSCLC. Nivolumab is one of the approved immunotherapeutic agents in the treatment of patients with metastatic NSCLC, who have failed after receiving chemotherapy. Our study explored the efficacy and safety of nivolumab in real-life setting in Türkiye. Nivolumab effectiveness was evaluated by overall survival (OS) and progression-free survival (PFS) rates. OS indicates the proportion of patients who are still alive at a given time after diagnosis or treatment initiation. PFS refers to "the length of time during and after cancer treatment that a person lives with the disease but does not get worse." In the present study, one-year OS for 244 patients who received nivolumab was 61.1% and one-year PFS was 26.4%. Nivolumab safety was evaluated based on the frequency of adverse events observed during nivolumab therapy. Of the patients 38.9% had at least one side effect, with fatigue being the most common (16.4%). Our results support the earlier studies and showed that nivolumab was a safe and effective agent and is associated with acceptable side effects.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Nivolumabe , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Sistema de Registros , Turquia/epidemiologia , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Metástase NeoplásicaRESUMO
Human papillomavirus (HPV), an oncogenic DNA virus, is the most common sexually transmitted virus and significant public health concern globally. Despite the substantial prevalence of HPV infection among men, routine testing remains elusive due to the lack of approved HPV tests and the complexity of detection methods. Various studies have explored the link between HPV and genitourinary cancers, revealing different associations influenced by geographic variation, histological subtype and methodological differences. These findings underscore the importance of further research to elucidate the role of HPV in male urogenital cancers. This comprehensive review delves into the intricate relationship between HPV and male genitourinary cancers, shedding light on the virus's oncogenic mechanisms and its reported prevalence. A deeper understanding of HPV's implications for male health is essential for advancing public health initiatives and reducing the burden of urogenital cancers worldwide.
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Carcinogênese , Papillomaviridae , Infecções por Papillomavirus , Neoplasias Urogenitais , Humanos , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Masculino , Neoplasias Urogenitais/virologia , Papillomaviridae/genética , Papillomaviridae/patogenicidade , Papillomaviridae/fisiologia , Prevalência , Papillomavirus HumanoRESUMO
PURPOSE OF REVIEW: Our review delves into the progress across urological malignancies and discusses ongoing challenges and future directions in antibody-drug conjugate (ADC) development, emphasising their transformative potential in cancer care. RECENT FINDINGS: ADCs have advanced from hematologic to solid tumours, notably in breast cancer, and are now pivotal in metastatic urological cancers as both monotherapies and in combination regimens, underscored by the FDA's approval of enfortumab vedotin and sacituzumab govitecan for metastatic urothelial cancer. Progress in metastatic prostate cancer, particularly with ADCs targeting PSMA and STEAP1, is noteworthy, although renal cell cancer presents ongoing challenges. There is a continual search for agents in the metastatic, relapsed testicular cancer landscape. ADCs have emerged as a pivotal innovation in oncology, blending targeted antibody therapy with potent cytotoxic drugs, significantly advancing treatment options for urological malignancies.
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Imunoconjugados , Neoplasias Urológicas , Humanos , Imunoconjugados/uso terapêutico , Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais/uso terapêuticoRESUMO
INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. MATERIALS AND METHODS: A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan-Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. RESULTS: The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. CONCLUSION: ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.
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Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias do Córtex Suprarrenal/terapia , Neoplasias do Córtex Suprarrenal/patologia , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/cirurgia , Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Carcinoma Adrenocortical/terapia , Carcinoma Adrenocortical/patologia , Carcinoma Adrenocortical/mortalidade , Carcinoma Adrenocortical/tratamento farmacológico , Carcinoma Adrenocortical/cirurgia , Adulto , Idoso , Turquia/epidemiologia , Prognóstico , Adulto Jovem , Análise de Sobrevida , Adolescente , Estimativa de Kaplan-Meier , Resultado do TratamentoRESUMO
Background: Medical practitioners are increasingly using artificial intelligence (AI) chatbots for easier and faster access to information. To our knowledge, the accuracy and availability of AI-generated chemotherapy protocols has not yet been studied. Methods: Nine simulated cancer patient cases were designed and AI chatbots, ChatGPT version 3.5 (OpenAI) and Bing (Microsoft), were used to generate chemotherapy protocols for each case. Results: Generated chemotherapy protocols were compared with the original protocols for nine simulated cancer patients. ChatGPT's overall performance was 5 out of 9 on protocol generation, and Bing's was 4 out of 9; this was statistically nonsignificant (p = 1). Conclusion: AI chatbots show both potential and limitations in generating chemotherapy protocols. The overall performance is low, and they should be used carefully in oncological practice.
[Box: see text].
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BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) have been associated with thrombotic events, although the association with thrombosis risk in different cancers remains poorly defined. METHODS: This meta-analysis included phase II and phase III clinical trials in which patients with metastatic prostate cancer were treated with PARPi either as monotherapy or in combination. The primary endpoints were the rates of thromboembolic events in prostate cancer patients. RESULTS: A total of 2210 and 1662 patients with prostate cancer were compared in the PARP inhibitor and control groups, respectively. 96 (4.3â¯%) and 37 (2.2â¯%) patients had thrombosis in the PARPi and control groups, respectively. PARPi had a statistically significant increased risk of thrombosis in prostate cancer patients (Odds Ratio (OR)=1.98, 95â¯% CI: 1.06-3.70, P=0.030). CONCLUSION: The heightened thrombotic risk associated with PARPi treatment in prostate cancer emphasizes the need for comprehensive management protocols to effectively reduce the risk and ensure safer outcomes.
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Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias da Próstata , Tromboembolia , Humanos , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/complicações , Tromboembolia/etiologia , Tromboembolia/epidemiologia , Tromboembolia/induzido quimicamente , Ensaios Clínicos Fase III como Assunto , Fatores de RiscoRESUMO
AIM: HER2-positive metastatic gastric cancer is still a highly fatal disease despite advances. We aimed to investigate the relationship between HER2/CEP17 ratio and survival in patients with HER2-positive metastatic gastric cancer. METHODS: A total of 99 patients from 8 different centers in Turkey were included in the study. Patients with HER2-positive metastatic gastric cancer and whose HER2/CEP17 ratio was examined were included in the study. Patients were divided into two groups according to HER2/CEP17 values, and survival analysis was performed. RESULTS: The median age was 64 (24-83) years. There were 74 (74.8%) male and 25 (25.2%) female patients. OS in the high HER2/CEP17 ratio group was 21.97 months (95% CI: 16.36-27.58), and in the low ratio group was 16.17 months (95% CI: 10.95-21.38) (p = 0.015). OS was 17.7 months (95% CI: 7.02-28.37) in the high HER2 gene copy number group and 10.13 months (5.55-14.71) in the group with low copy number (p = 0.03). PFS was 10.94 months (95% CI: 7.55-14.33) in the group with high HER2 gene copy number and 7.56 months (4.62-10.49) in the low copy number group (p = 0.06). CONCLUSION: Patients with both high HER2 gene amplification and high HER2/CEP17 ratio had better OS. The PFS of the group with high HER2 gene amplification was also better. To our knowledge, this is the first study in the literature showing that the HER2/CEP17 ratio affects survival in patients with metastatic gastric cancer.
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Receptor ErbB-2 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Receptor ErbB-2/metabolismo , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Prognóstico , Taxa de Sobrevida , Turquia/epidemiologia , Cromossomos Humanos Par 17/genética , Hibridização in Situ FluorescenteRESUMO
Aim: This study aimed to investigate the association between microsatellite instability (MSI) status and inflammatory indicators in patients with cancer. Patients & methods: A total of 204 patients with various cancer diagnoses, including 102 with MSI-high (MSI-H) and 102 with microsatellite stable tumors, were enrolled. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP)-to-albumin ratio and systemic immune-inflammation index were evaluated. Results: In microsatellite stable patients, NLR, LMR, PLR and systemic immune-inflammation index were significantly linked to worse survival in univariate analysis, and having a LMR ≤2.6 negatively affected survival in multivariate analysis, although these indicators did not affect the survival of MSI-H patients. Conclusion: The impact of chronic inflammation on survival varies with MSI status. Further research is needed for targeted therapies in different tumors.
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Instabilidade de Microssatélites , Neoplasias , Humanos , Linfócitos , Proteína C-Reativa , Inflamação , Neutrófilos , Estudos RetrospectivosRESUMO
Histamine and H1 receptors play a crucial role in the tumor microenvironment. Preclinical data showed that concomitant use of antihistamines and immune checkpoint inhibitors (ICIs) might increase the effect of ICIs. This study aimed to evaluate the impact of antihistamines on the oncological outcomes of ICIs. This retrospective study was conducted in a tertiary cancer center. Advanced cancer patients treated with ICIs were included in this study. A total of 133 patients receiving ICIs in the metastatic setting were included. Melanoma (33.1%) was the most common tumor type. The most common ICI was nivolumab (63.2%). Fifty-five (38.4%) patients received antihistamines concomitantly with ICIs. The most common antihistamine was pheniramine (85.5%). The median progression-free survival (PFS) (8.2 vs. 5.1 months, P â =â 0.016) and overall survival (OS) (16.2 vs. 7.7 months, P â =â 0.002) were longer in patients receiving antihistamines concomitantly with ICIs. In multivariate analysis, PFS [hazard ratio (HR)â =â 0.63, 95% CI: 0.40-0.98, P â =â 0.042] and OS (HRâ =â 0.49, 95% CI: 0.29-0.81, P â =â 0.006) were also better in those patients after adjusting for confounding factors, such as performance status, bone or liver metastasis, and concurrent chemotherapy. This study suggested that antihistamines may enhance the efficacy of ICIs in patients with advanced cancer. If validated in prospective trials, antihistamines and ICIs combinations might be new options to improve oncological outcomes.
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Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Microambiente TumoralRESUMO
INTRODUCTION: Immunotherapy (IO)-based combination therapies have emerged as the standard of care for first-line treatment of metastatic renal cell carcinoma (mRCC) among patients classified as intermediate and poor risk. However, in the favorable risk group, the available data remains less compelling. This study aims to assess and compare the effectiveness of IO-based combination therapies versus tyrosine kinase inhibitor (TKI) monotherapy in patients with favorable risk group according to the International mRCC Database Consortium (IMDC). METHODS: Recent update data from phase-III RCTs of IO-based combinations approved by the Food and Drug Administration were used. Studies that provided data on progression free survival (PFS) and overall survival (OS) of IMDC favorable risk were included in the analysis. RESULTS: A cohort of 1,088 patients categorized within the IMDC favorable risk group was enrolled for analysis. In comparison to sunitinib, the combination of immunotherapy (IO) and tyrosine kinase inhibitor (TKI) exhibited a reduction in the risk of disease progression (HR = 0.67, 95 % CI: 0.55-0.82; p < 0.001). Conversely, the combination of IO and IO displayed an elevated risk of disease progression (HR = 1.60, 95 % CI: 1.13-2.26; p = 0.008). However, neither the IO plus TKI (HR = 0.99, 95 % CI: 0.79-1.24; p = 0.92) nor IO plus IO (HR = 0.94, 95 % CI: 0.64-1.37; p = 0.75) combinations demonstrated a noteworthy improvement in overall survival (OS). Notably, within the IO plus TKI subgroup, combination therapy yielded a higher objective response rate (ORR) (OR = 0.40, 95 % CI: 0.28-0.57; p < 0.001). On the other hand, the IO plus IO combination displayed a lower ORR than sunitinib (OR = 2.54, 95 % CI: 1.51-4.27; p < 0.001). CONCLUSIONS: In the first-line treatment of IMDC favorable-risk mRCC, IO and TKI combinations show enhanced progression-free survival and response rate without improving overall survival. This emphasizes the demand for further exploration of combination therapies in this patient group.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/patologia , Sunitinibe/uso terapêutico , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Progressão da Doença , Estudos RetrospectivosRESUMO
INTRODUCTION: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors. METHODS: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey. The primary endpoints were the overall response (ORR) and disease control rate (DCR). RESULTS: The cohort's median age was 56, and 53.8% of the patients were male. The most frequent diagnosis was sarcoma (29%), and 81.7% of the patients were previously treated with at least one line of systemic therapy in the advanced stage. The ORR and DCR were 36.8% and 63.2%, respectively. The germ cell tumors had the lowest ORR (0%), while the Merkel cell carcinoma had the highest ORR to ICIs (57.1%). Patients treated with ICI + ICI or ICI plus chemotherapy combinations had higher ORR (55.2% vs. 27.6%, p = 0.012) and DCR (82.8% vs. 53.4%, p = 0.008). The median OS was 13.47 (95% CI: 7.79-19.15) months, and the six and 12-month survival rates were 71% and 52%. The median duration of response was 16.59 months, and the 12-month progression-free survival rate was 66% in responders. The median time-to-treatment failure was 5.06 months (95% CI: 3.42-6.71). Three patients had high-grade irAEs with ICIs (grade 3 colitis, grade 3 gastritis, and grade 3 encephalitis in one patient each). CONCLUSION: We observed over 30% ORR and a 13-month median OS in patients with rare cancers treated with ICI monotherapy or ICI plus CT combinations. The response rates to ICIs or ICIs plus CT significantly varied across different tumor types. Responding patients had over 2 years of survival, highlighting a need for further trials with ICIs for patients with rare tumors.
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Protocolos de Quimioterapia Combinada Antineoplásica , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Turquia , Idoso , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Neoplasias/terapia , Neoplasias/imunologia , Neoplasias/patologia , Imunoterapia/métodos , Doenças Raras/tratamento farmacológico , Doenças Raras/patologia , Doenças Raras/mortalidade , Adulto Jovem , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
The treatment landscape for castration-resistant prostate cancer (mCRPC) is undergoing significant advancements, particularly with the emergence of poly(ADP-ribose) polymerase inhibitors and their recent US FDA authorizations. The combination of olaparib with abiraterone and prednisone/prednisolone has gained approval for mCRPC patients harboring confirmed BRCA mutations. Subsequently, talazoparib in combination with enzalutamide was approved for patients with mutations in homologous recombination repair genes. Nevertheless, emerging evidence suggests that these treatments may confer benefits irrespective of specific biomarkers. While the understanding of biomarkers in therapy selection for mCRPC is expanding, further data are warranted to provide comprehensive elucidation for guiding clinical practice.
Assuntos
Inibidores de Poli(ADP-Ribose) Polimerases , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Mutação , BiomarcadoresRESUMO
BACKGROUND: No new agent has improved overall survival in patients with unresectable or metastatic urothelial carcinoma when added to first-line cisplatin-based chemotherapy. METHODS: In this phase 3, multinational, open-label trial, we randomly assigned patients with previously untreated unresectable or metastatic urothelial carcinoma either to receive intravenous nivolumab (at a dose of 360 mg) plus gemcitabine-cisplatin (nivolumab combination) every 3 weeks for up to six cycles, followed by nivolumab (at a dose of 480 mg) every 4 weeks for a maximum of 2 years, or to receive gemcitabine-cisplatin alone every 3 weeks for up to six cycles. The primary outcomes were overall and progression-free survival. The objective response and safety were exploratory outcomes. RESULTS: A total of 608 patients underwent randomization (304 to each group). At a median follow-up of 33.6 months, overall survival was longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for death, 0.78; 95% confidence interval [CI], 0.63 to 0.96; P = 0.02); the median survival was 21.7 months (95% CI, 18.6 to 26.4) as compared with 18.9 months (95% CI, 14.7 to 22.4), respectively. Progression-free survival was also longer with nivolumab-combination therapy than with gemcitabine-cisplatin alone (hazard ratio for progression or death, 0.72; 95% CI, 0.59 to 0.88; P = 0.001). The median progression-free survival was 7.9 months and 7.6 months, respectively. At 12 months, progression-free survival was 34.2% and 21.8%, respectively. The overall objective response was 57.6% (complete response, 21.7%) with nivolumab-combination therapy and 43.1% (complete response, 11.8%) with gemcitabine-cisplatin alone. The median duration of complete response was 37.1 months with nivolumab-combination therapy and 13.2 months with gemcitabine-cisplatin alone. Grade 3 or higher adverse events occurred in 61.8% and 51.7% of the patients, respectively. CONCLUSIONS: Combination therapy with nivolumab plus gemcitabine-cisplatin resulted in significantly better outcomes in patients with previously untreated advanced urothelial carcinoma than gemcitabine-cisplatin alone. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 901 ClinicalTrials.gov number, NCT03036098.).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células de Transição , Cisplatino , Gencitabina , Nivolumabe , Neoplasias da Bexiga Urinária , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Gencitabina/administração & dosagem , Gencitabina/efeitos adversos , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Administração IntravenosaRESUMO
INTRODUCTION: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs). METHODS: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey. RESULTS: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, Pâ =â .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, Pâ =â .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (Pâ <â .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment. CONCLUSIONS AND RELEVANCE: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET.