ABSTRACT
PURPOSE: Intestinal dysbiosis has emerged as a biomarker of response to immune checkpoint inhibitors (ICIs). It can be caused by antibiotics, although it may also result from the use of other drugs that have been studied to a lesser extent. The objective of our study was to analyze the association between the use of potentially dysbiosis-related drugs and survival in patients treated with ICIs in the clinical practice. MATERIALS AND METHODS: A retrospective, multicenter, cohort study was conducted. Clinicopathological variables were collected and the concomitant use of drugs was analyzed. A descriptive analysis of variables and overall survival, estimated by the Kaplan-Meier method, was performed, and association with various independent variables was assessed using Cox regression. RESULTS: We included 253 patients, mainly with non-small cell lung cancer and melanoma. The most commonly used drugs were acid reducers, prescribed to 55.3% of patients, followed by corticosteroids (37.9%), anxiolytic drugs (35.6%), and antibiotics (20.5%). The use of acid reducers (9 vs. 18 months, P < .0001), antibiotics (7 vs. 15 months, P < .017), anxiolytic drugs (8 vs. 16 months, P < .015), and corticosteroids (6 vs. 19 months, P < .00001) was associated with poorer overall survival. Furthermore, the greater the number of drugs used concomitantly with ICIs, the higher the risk of death (1 drug: hazard ratio, 1.88; CI 95%, 1.07-3.30; 4 drugs: hazard ratio, 4.19; CI9 5%, 1.77-9.92; P < .001). CONCLUSION: Response to ICIs may be influenced by the use of drugs that lead to intestinal dysbiosis. Although a confirmatory prospective controlled study is required, our findings should be taken into account when analyzing ICI efficacy.
Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Dysbiosis/chemically induced , Immune Checkpoint Inhibitors/therapeutic use , Lung Neoplasms/drug therapy , Melanoma/drug therapy , Adrenal Cortex Hormones/adverse effects , Adult , Aged , Aged, 80 and over , Antacids/adverse effects , Anti-Anxiety Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/mortality , Female , Humans , Lung Neoplasms/mortality , Male , Melanoma/mortality , Middle Aged , Retrospective StudiesABSTRACT
The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents
No disponible
Subject(s)
Humans , Carcinoma, Transitional Cell/therapy , Urinary Bladder Neoplasms/therapy , Muscle Neoplasms/therapy , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents/therapeutic use , Neoplasm Invasiveness/pathology , Muscle Neoplasms/secondary , Cystectomy/methods , Practice Patterns, Physicians'ABSTRACT
The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.
Subject(s)
Muscle Neoplasms/therapy , Practice Guidelines as Topic/standards , Urinary Bladder Neoplasms/therapy , Clinical Trials as Topic , Combined Modality Therapy , Disease Management , Humans , Muscle Neoplasms/secondary , Neoplasm Invasiveness , Prognosis , Societies, Medical , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: Cancer-specific survival for patients with clinical stage I (CSI) germ cell testicular cancer (GCTC) is outstanding after inguinal orchidectomy regardless the treatment utilized. This study evaluated whether active surveillance (AS) of such patients yielded similar health outcomes to other therapeutic strategies such as adjuvant chemotherapy, radiotherapy or primary retroperitoneal lymphadenectomy as described in the literature. PATIENTS AND METHODS: Patients with CSI GCTC were screened between January 2012 and December 2016. Patients had previously undergone inguinal orchidectomy as the primary treatment and chosen AS as their preferred management strategy after receiving information about all available strategies. RESULTS: Out of 91 patients screened, 82 patients selected AS as their preferred management strategy. Relapse rate in the overall population was 20% (95% CI 12-30) and median time to relapse was 11.5 months (range 1.0-35.0). In patients with seminomatous tumors, relapse rate decreased to 13% and median time to relapse was 13 months; whereas in patients with non-seminomatous tumors, relapse rate was 33% (IA) or 29% (IB) and median time to relapse was 12 months in stage IA and 4.5 months in stage IB patients. All relapses were rescued with three or four cycles of chemotherapy and two also required a retroperitoneal lymphadenectomy. All patients are currently alive and free of disease. CONCLUSIONS: The clinical outcomes of patients with CSI GCTC managed by AS in this series were excellent. This strategy limited the administration of active treatments specifically to the minority of patients who relapsed without compromising performance.
Subject(s)
Multimodal Imaging/methods , Neoplasms, Germ Cell and Embryonal/prevention & control , Orchiectomy/mortality , Population Surveillance , Testicular Neoplasms/prevention & control , Watchful Waiting/statistics & numerical data , Adolescent , Adult , Aged , Disease Management , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/surgery , Prognosis , Retrospective Studies , Survival Rate , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/surgery , Watchful Waiting/standards , Young AdultABSTRACT
The original article shows two mistakes, which are listed here.
ABSTRACT
Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma (AU)
No disponible
Subject(s)
Humans , Male , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Androgen Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Practice Guidelines as Topic , Neoplasm Metastasis/therapy , Neoplasm Recurrence, Local/drug therapy , Abiraterone Acetate/therapeutic useABSTRACT
Androgen deprivation treatment was the only treatment available for metastatic prostate cancer until recently, with docetaxel as the only treatment with a proven survival benefit in castration-resistant prostate cancer (CRPC). Several drugs have been approved in the castration-resistant disease (sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, radium-223). More recently, docetaxel and abiraterone have been moved to the hormone-sensitive disease setting, achieving better patient survival. The purpose of this article is to define the state of the art in the treatment of prostate carcinoma.
Subject(s)
Antineoplastic Agents/therapeutic use , Prostatic Neoplasms/drug therapy , Humans , MaleABSTRACT
BACKGROUND: Clear-cell renal cell carcinoma (ccRCC) is a heterogeneous disease with a different clinical behavior and response to targeted therapies. Differences in hypoxia-inducible factor (HIF) expression have been used to classify von Hippel-Lindau gene (VHL)-deficient ccRCC tumors. c-Myc may be driving proliferation in HIF-2α-expressing tumors in a growth factor-independent manner. OBJECTIVE: To explore the HIF-1α, HIF-2α and c-Myc baseline expression as potential predictors of sunitinib outcome as well as the effectiveness and safety with sunitinib in patients with metastatic ccRCC in routine clinical practice. METHODS: This was an observational and prospective study involving 10 Spanish hospitals. Formalin-fixed, paraffin-embedded primary tumor samples from metastatic ccRCC patients who received sunitinib as first-line treatment were analyzed. Association between biomarker expression and sunitinib treatment outcomes was evaluated. Kaplan-Meier method was applied to measure progression-free survival (PFS) and overall survival. RESULTS: Eighty-one patients were included: median PFS was 10.8 months (95% CI: 7.4-13.5 months), median overall survival was 21.8 months (95% CI: 14.7-29.8 months) and objective response rate was 40.7%, with 7.4% of patients achieving a complete response. Molecular marker staining was performed in the 69 available tumor samples. Significant association with lower PFS was identified for double c-Myc/HIF-2α-positive staining tumors (median 4.3 vs 11.5 months, hazard ratio =2.64, 95% CI: 1.03-6.80, P=0.036). A trend toward a lower PFS was found in positive c-Myc tumors (median 5.9 vs 10.9 months, P=0.263). HIF-1α and HIF-2α expression levels were not associated with clinical outcome. CONCLUSION: These preliminary results suggest that predictive subgroups might be defined based on biomarkers such as c-Myc/HIF-2α. Further validation with more patients will be needed in order to confirm it. Outcomes with sunitinib in metastatic ccRCC in daily clinical practice resemble those obtained in clinical trials.
ABSTRACT
BACKGROUND: Patients with metastatic renal carcinoma (mRCC) treated with first-line pazopanib were not included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. SPAZO (NCT02282579) was a nation-wide retrospective observational study designed to assess the effectiveness and validate the IMDC prognostic model in patients treated with first-line pazopanib in clinical practice. PATIENTS AND METHODS: Data of 278 patients, treated with first-line pazopanib for mRCC in 34 centres in Spain, were locally recorded and externally validated. Mean age was 66 years, there were 68.3% male, 93.5% clear-cell type, 74.8% nephrectomized, and 81.3% had ECOG 0-1. Metastatic sites were: lung 70.9%, lymph node 43.9%, bone 26.3%, soft tissue/skin 20.1%, liver 15.1%, CNS 7.2%, adrenal gland 6.5%, pleura/peritoneum 5.8%, pancreas 5%, and kidney 2.2%. After median follow-up of 23 months, 76.4% had discontinued pazopanib (57.2% due to progression), 47.9% had received second-line targeted therapy, and 48.9% had died. RESULTS: According to IMDC prognostic model, 19.4% had favourable risk (FR), 57.2% intermediate risk (IR), and 23.4% poor risk (PR). No unexpected toxicities were recorded. Response rate was 30.3% (FR: 44%, IR: 30% PR: 17.3%). Median progression-free survival (whole population) was 11 months (32 in FR, 11 in IR, 4 in PR). Median and 2-year overall survival (whole population) were 22 months and 48.1%, respectively (FR: not reached and 81.6%, IR: 22 and 48.7%, PR: 7 and 18.8%). These estimations and their 95% confidence intervals are fully consistent with the outcomes predicted by the IMDC prognostic model. CONCLUSION: Our results validate the IMDC model for first-line pazopanib in mRCC and confirm the effectiveness and safety of this treatment.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Molecular Targeted Therapy , Prognosis , Pyrimidines/administration & dosage , Sulfonamides/administration & dosage , Adult , Aged , Carcinoma, Renal Cell/pathology , Databases, Factual , Disease-Free Survival , Female , Humans , Indazoles , Kaplan-Meier Estimate , Male , Middle Aged , Pyrimidines/adverse effects , Retrospective Studies , Risk Factors , Spain , Sulfonamides/adverse effectsABSTRACT
Prostate cancer is the most common male malignancy in the Western world. Once it metastasizes, it is incurable. The current gold standard for metastatic disease is the combined docetaxel/prednisone regimen. Prostate cancer shows several characteristics that make it a suitable candidate for immunotherapy, as recently exemplified by the approval of sipuleucel-T, the first vaccine to treat any malignancy. Here, we review different tumor associated antigen immunotherapy strategies currently being investigated, from a humanized radiolabeled monoclonal antibody (J-591) that targets radiation into tumor cells, moving on to vaccines and through to immunomodulator agents such as anti-CPLA-4 and anti-PD-1 monoclonal antibodies that activate T-cell responses via immune checkpoint inhibition. We explore different opinions on the best approach to integrate immunotherapy into existing standard therapies, such as androgen-deprivation therapy, radiotherapy or chemotherapy, and review different combination sequences, patient types and time points during the course of the disease to achieve a lasting immune response. We present data from recent phase III clinical trials that call for a change in trial endpoint design with immunotherapy agents, from the traditional tumor progression to overall survival and how such trials should include immune response measurements as secondary or intermediate endpoints to help identify patient clinical benefit in the earlier phases of treatment. Finally, we join in the recent questioning on the validity of RECIST criteria to measure response to immunotherapeutic agents, as initial increases in the size of tumors/lymph nodes, which are part of a normal immune response, could be categorized as disease progression under RECIST (AU)
No disponible
Subject(s)
Humans , Male , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/therapy , Immunotherapy/methods , Immunotherapy/trends , Immunotherapy , Immunization, Passive/instrumentation , Immunization, Passive/methods , Antibodies, Monoclonal/therapeutic use , Prostate-Specific Antigen/isolation & purification , Prostatic Neoplasms/immunology , Prednisone/therapeutic use , Neoplasm Metastasis/immunology , Neoplasm Metastasis/physiopathology , Neoplasm Metastasis/therapy , Prostate-Specific Antigen/immunology , Prostate-Specific Antigen/therapeutic use , Acid Phosphatase/immunology , Acid Phosphatase/therapeutic useABSTRACT
Prostate cancer is the most common male malignancy in the Western world. Once it metastasizes, it is incurable. The current gold standard for metastatic disease is the combined docetaxel/prednisone regimen. Prostate cancer shows several characteristics that make it a suitable candidate for immunotherapy, as recently exemplified by the approval of sipuleucel-T, the first vaccine to treat any malignancy. Here, we review different tumor-associated antigen immunotherapy strategies currently being investigated, from a humanized radiolabeled monoclonal antibody (J-591) that targets radiation into tumor cells, moving on to vaccines and through to immunomodulator agents such as anti-CPLA-4 and anti-PD-1 monoclonal antibodies that activate T-cell responses via immune checkpoint inhibition. We explore different opinions on the best approach to integrate immunotherapy into existing standard therapies, such as androgen-deprivation therapy, radiotherapy or chemotherapy, and review different combination sequences, patient types and time points during the course of the disease to achieve a lasting immune response. We present data from recent phase III clinical trials that call for a change in trial endpoint design with immunotherapy agents, from the traditional tumor progression to overall survival and how such trials should include immune response measurements as secondary or intermediate endpoints to help identify patient clinical benefit in the earlier phases of treatment. Finally, we join in the recent questioning on the validity of RECIST criteria to measure response to immunotherapeutic agents, as initial increases in the size of tumors/lymph nodes, which are part of a normal immune response, could be categorized as disease progression under RECIST.
Subject(s)
Antineoplastic Agents/therapeutic use , Cancer Vaccines/therapeutic use , Combined Modality Therapy , Immunotherapy , Prostatic Neoplasms/therapy , Antibodies, Monoclonal/therapeutic use , CTLA-4 Antigen/immunology , Humans , Immunomodulation , Male , Programmed Cell Death 1 Receptor/immunology , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/therapy , Response Evaluation Criteria in Solid TumorsABSTRACT
Aggressive non-Hodgkin's lymphomas (NHL) in localized stages I and II, without bulky areas and a fair International Prognostic Factor (IPI) (30% of all cases) have high possibilities of cure (80%) when treated with combined chemotherapy, CHOP or CHOP-like (3-4 courses) followed by locoregional radiation therapy. Localized aggressive non-Hodgkin's lymphomas with signs of poor prognosis or advanced stages (III and IV) must be treated with rituximab-containing immunochemotherapy. As second line in responding patients (DHAP, ESHAP, MINE, VIM, DICE, etc., and rituximab) high doses chemotherapy with hematopoietic growth factor support should be considered, although not in refractory patients.
Subject(s)
Lymphoma, Large B-Cell, Diffuse/therapy , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin/therapy , Neoplasm StagingABSTRACT
Los linfomas agresivos en estadios localizados I y II, sin masas voluminosas y con un Índice Pronóstico Internacional (IPI) bajo (30% de los casos) tienen altas posibilidades de curación, cerca del 80% con el tratamiento combinado de quimioterapia tipo CHOP (3-4 ciclos) seguido de radioterapia (RT) sobre áreas afectas. En los linfomas agresivos localizados con signos de mal pronóstico o estadios avanzados (III-IV), el tratamiento es la inmunoquimioterapia con rituximab. Como segunda línea en pacientes quimiosensibles (DHAP, ESHAP, MINE, VIM, DICE, etc., más rituximab) deben valorarse las altas dosis con soporte hematopoyético, no así en los refractarios (AU)
Aggressive non-Hodgkins lymphomas (NHL) in localized stages I and II, without bulky areas and a fair International Prognostic Factor (IPI) (30% of all cases) have high possibilities of cure (80%) when treated with combined chemotherapy, CHOP or CHOP-like (3-4 courses) followed by locoregional radiation therapy. Localized aggressive non-Hodgkins lymphomas with signs of poor prognosis or advanced stages (III and IV) must be treated with rituximab-containing immunochemotherapy. As second line in responding patients (DHAP, ESHAP, MINE, VIM, DICE, etc., and rituximab) high doses chemotherapy with hematopoietic growth factor support should be considered, although not in refractory patients (AU)