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BACKGROUND: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. METHODS: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. RESULT: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. CONCLUSION: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors.
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Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Nomogramas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Femenino , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/inmunología , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Subgrupos Linfocitarios/inmunología , Adulto , Recuento de LinfocitosRESUMEN
Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4+ T cells expressing programmed cell death 1 (PD-1) are enriched for latent HIV, making antibody to PD-1 a potential strategy to target the latent reservoir. Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4+ counts ≥350 cells/µL who received 2 infusions of cemiplimab versus placebo. The primary outcome was safety, defined as any grade 3 or higher adverse event (AE) or any immune-related AE (irAE). Changes in HIV-1-specific polyfunctional CD4+ and CD8+ T-cell responses were evaluated. Results: Five men were enrolled (median CD4+ count, 911â cells/µL; median age, 51 years); 2 received 1 dose of cemiplimab, 2 received 2 doses, and 1 received placebo. One participant had a probable irAE (thyroiditis, grade 2); another had a possible irAE (hepatitis, grade 3), both after a single low-dose (0.3 mg/kg) infusion. The Safety Monitoring Committee recommended no further enrollment or infusions. All 4 cemiplimab recipients were followed for 48 weeks. No other cemiplimab-related serious AEs, irAEs, or grade 3 or higher AEs occurred. One 2-dose recipient of cemiplimab had a 6.2-fold increase in polyfunctional, Gag-specific CD8+ T-cell frequency with supportive increases in plasma HIV RNA and decreases in total HIV DNA. Conclusions: One of 4 participants exhibited increased HIV-1-specific T-cell responses and transiently increased HIV-1 expression following 2 cemiplimab infusions. The occurrence of irAEs after a single, low dose may limit translating the promising therapeutic results of cemiplimab for cancer to immunotherapeutic and latency reversal strategies for HIV. Clinical Trials Registration. NCT03787095.
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This study aimed to investigate the associations between the clinical characteristics and effectiveness of anti-PD-1 inhibitors in patients with EGFR-sensitive mutations, aiming to identify the potential subgroup of patients who might benefit from anti-PD-1 inhibitor treatment. Patients with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-sensitive mutations who received subsequent anti-PD-1 inhibitors in combination with chemotherapy/antiangiogenic agents or alone after progression to tyrosine kinase inhibitors (TKIs) were screened. Clinical characteristics, including hematological parameters, were investigated for potential correlations with clinical outcomes. Subgroup and multivariate analyses were used for further confirmation of the relationship. Kaplan-Meier curves and Cox survival regression models using the log-rank test were used for progression-free survival (PFS) and overall survival (OS) assessments between the groups. Multiple regression analysis was performed using the standard regression coefficient values. The Wilcoxon test was used for the analysis of the variation in NLR. P ≤ 0.05 was considered to indicate statistical significance. This study was a retrospective study. Twenty-two patients met the inclusion criteria and were included in the study. The median PFS was 3.05 months (95% CI, 2.9-10.2 months). The median OS was 7.30 months (95% CI, 5.2-18.1 months). PFS in low neutrophil to lymphocyte ratio (NLR ≤ 4) was significantly longer than high NLR (NLR > 4, 5.7 months versus 2.0 months, HR, 0.35, 95% CI, 0.08-0.63, P = 0.0083). The OS in the low NLR group was also significantly better than that in the high NLR group (OS, 21.3 months versus 5.0 months, HR, 0.33; 95% CI, 0.09-0.74; P = 0.0163). In the multivariate analysis, NLR was the only significant factor for OS benefits (ß = 3.535, 95% CI, 1.175-10.636, P = 0.025). Further investigation revealed that front-line TKIs exposure may contribute to the elevation or decrease of NLR, and finally lead to different efficacy outcomes by anti-PD-1 inhibitors. The findings suggest that a portion of advanced NSCLC patients with low NLR characteristics (NLR ≤ 4), even those harboring EGFR-sensitive mutations, could benefit from anti-PD-1 inhibitors as further line treatment after progression to EGFR-TKIs.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios Retrospectivos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neutrófilos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Pronóstico , Antineoplásicos/uso terapéutico , Linfocitos , Receptores ErbB , Mutación , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
Thyroid metastases secondary to triple-negative breast cancer are sporadic. Diagnosis usually requires fine needle aspiration biopsy (FNAB) and immunohistochemistry. There are no treatment guidelines for this type of cancer, and to date, reports of chemotherapy combined with immunotherapy in thyroid metastases are very rare. Here, we first report the effectiveness of anti-PD-1 inhibitor in combination with chemotherapy for the treatment of metastatic thyroid cancer secondary to advanced triple-negative breast cancer with high expression of programmed cell death ligand 1 (PD-L1). Following six cycles of albumin paclitaxel (400mg d1/21 days) plus PD-1 antibody inhibitor (Sindilizumab 200mg d1/21 days), the patient experienced significant relief of neck swelling and obstructive feeding, both the thyroid metastases and the right breast lesion regressed completely following six cycles of treatment. Chemotherapy combined with immunotherapy may provide a new direction for unresectable advanced thyroid metastases.
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Objective: To investigate the clinical efficacy and safety of anlotinib combined with anti-PD-1 inhibitors in the 2nd or later-line treatment of advanced solid tumors. Patients and Methods: A total of 63 patients with advanced solid tumors who had failed or could not endure the adverse reactions after receiving first-line or more systematic treatment in the Second Affiliated Hospital of Harbin Medical University from March 2019 to April 2023 were treated with anlotinib Hydrochloride capsule combined with anti-PD-1 inhibitors. The efficacy and adverse reactions were evaluated according to RECIST1.1 and NCICTC4.0 standards. Results: The percentage of overall response rate of 63 patients during the combination administration indicated that complete response was 1.6% (n=1), partial response was 23.8% (n=15), stable disease was 39.7% (n=25) and progressive disease was 34.9% (n=22), yielding objective response rate (ORR) of 25.4% and disease control rate (DCR) of 65.1%. Furthermore, the median PFS of 63 patients with advanced solid tumors was 7 months and the median OS was not reached, and the median follow-up time is 4.5 months. In subgroup analysis, there was no significant difference in PFS between first-line, second-line, third-line and above (p=0.631); there was no significant difference in PFS between PD-1 positive patients and PD-1 negative patients (p=0.094); there was no significant difference in PFS between patients who had previously used anti-PD-1 inhibitors and patients who had not used before (p=0.204). The most common adverse reactions were hypertension, hand-foot syndrome, and fatigue, with an incidence of 28.4% (18/63), 25.6% (14/63), and 25.6% (14/63), respectively. Most of the adverse reactions were grade 1-2, and there were no grade 4 adverse reactions. Conclusion: Anlotinib combined with anti-PD-1 inhibitors demonstrated promising efficacy and tolerable safety for patients with advanced solid tumors in the 2nd or later-line treatment.
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Over the past few decades, immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic options for the treatment of various cancers. These novel treatments effectively target key mediators of immune checkpoint pathways. Currently, ICIs primarily consist of monoclonal antibodies that specifically block cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and lymphocyte activation gene 3 protein (LAG-3). Despite the notable efficacy of ICIs in cancer treatment, they can also trigger immune-related adverse events (irAEs), which present as autoimmune-like or inflammatory conditions. IrAEs have the potential to affect multiple organ systems, with cutaneous toxicities being the most commonly observed. Although cutaneous irAEs are typically of low-grade severity and can usually be managed effectively, there are cases where severe irAEs can become life-threatening. Therefore, early recognition and a comprehensive understanding of the mechanisms underlying cutaneous irAEs are crucial for improving clinical outcomes in cancer patients. However, the precise pathogenesis of cutaneous irAEs remains unclear. This review focuses on the skin manifestations induced by ICIs, the prognosis related to cutaneous irAEs, and the exploration of potential mechanisms involved in cutaneous irAEs.
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Antineoplásicos Inmunológicos , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Neoplasias/tratamiento farmacológico , Anticuerpos Monoclonales/efectos adversos , PronósticoRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICI) are increasingly the mainstay of oncology treatment. Immune-related adverse events (irAEs) from ICI therapy differ from cytotoxic adverse events. Cutaneous irAEs are one of the most common irAEs and require careful attention to optimize the quality of life for oncology patients. PATIENT AND METHODS: These are two cases of patients with advanced solid-tumour malignancies treated with PD-1 inhibitor therapy. RESULTS: Both patients developed multiple pruritic hyperkeratotic lesions, which were initially diagnosed as squamous cell carcinoma from skin biopsies. The presentation as squamous cell carcinoma was atypical and, upon further pathology review, the lesions were more in keeping with a lichenoid immune reaction stemming from the immune checkpoint blockade. With the use of oral or topical steroids and immunomodulators, the lesions resolved. CONCLUSIONS: These cases emphasize that patients on PD-1 inhibitor therapy who develop lesions resembling squamous cell carcinoma on initial pathology may require an additional pathology review to assess for immune-mediated reactions, allowing appropriate immunosuppressive therapy to be initiated.
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Antineoplásicos , Carcinoma de Células Escamosas , Humanos , Receptor de Muerte Celular Programada 1 , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Calidad de Vida , Carcinoma de Células Escamosas/tratamiento farmacológicoRESUMEN
Introduction: Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced NSCLC. Nevertheless, these responses are limited to a few patients, and most responders have disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between long-term responders (LTRs) and non-LTRs. Methods: We retrospectively analyzed consecutive patients with advanced NSCLC who received antiprogrammed cell death protein 1 (PD-1) inhibitor monotherapy (nivolumab) from December 22, 2015, to May 31, 2017. Patients who obtained a clinical benefit for more than 6 months were referred to as "responders"; among these, individuals who had a durable response for more than 2 years were defined as "LTRs." Those with a clinical benefit for less than 2 years were defined as "non-LTRs." Results: A total of 212 patients received anti-PD-1 inhibitor monotherapy. The responders accounted for 35% (75 of 212) of the patients. Of these, 29 (39%) were LTRs and 46 (61%) were non-LTRs. The overall response rate and median tumor shrinkage in the LTR group were significantly higher than those in the non-LTR group (76% versus 35%, p < 0.0001, and 66% versus 16%, p < 0.001, respectively). The groups had no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-month post-treatment initiation. Conclusions: Significant tumor shrinkage was associated with a long-term response to an anti-PD-1 inhibitor. Nevertheless, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders.
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PURPOSE: The prognosis of patients with NRAS-mutant melanoma is rather poor. Immunotherapy and targeted therapy have revolutionized anti-tumor therapy, especially for melanoma. In this study, we retrospectively summarized the real-world experience of systematic treatment for NRAS-mutant melanoma patients in this new era. PATIENTS AND METHODS: The respective cohort included NRAS-mutant melanoma patients with metastatic or unresectable disease of Sun Yat-sen University Cancer Center (SYSUCC) from January 2018 to July 2022. The data about the clinical features and impact for systemic therapy of NRAS-mutant patients were collected and analyzed. RESULTS: At data cutoff, 44 patients (19, 11, and 14 for acral, cutaneous, and mucosal ones, respectively) with NRAS-mutant were assessed. In addition, the median time of follow-up was 22.0 months. The immunotherapy-based combined treatment not only significantly improved the progression-free survival (PFS) (P = 0.006, HR 0.322), but was also accompanied by a higher objective response rate (ORR) (18.2%), disease control rate (DCR) (72.7%) than those of cytotoxic therapy or immunotherapy alone for advanced patients as first-line treatment. Nab-paclitaxel combined with anti-PD-1 inhibitor tended to produce better clinical benefit for the first-line treatment, especially for patients with acral melanoma. In addition, the tyrosine kinase inhibitor (TKI) combined with anti-PD-1 inhibitor also seemed to provide longer duration of response (DOR) for some patients. But combined therapy did not prolong the overall survival (OS) of NRAS-mutant patients. The combined therapy was well tolerated. Most adverse events were moderate and controllable. CONCLUSION: In conclusion, PD-1 inhibitor-based combined therapy increased clinical benefit for advanced patients with NRAS-mutant melanoma.
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Melanoma , Neoplasias Cutáneas , Humanos , Estudios Retrospectivos , Pueblos del Este de Asia , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Pronóstico , Proteínas de la Membrana/genética , GTP Fosfohidrolasas/genéticaRESUMEN
Immune checkpoint inhibitors (ICIs) have emerged as novel options that are effective in treating various cancers. They are monoclonal antibodies that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). However, activation of the immune systems through ICIs may concomitantly trigger a constellation of immunologic symptoms and signs, termed immune-related adverse events (irAEs), with the skin being the most commonly involved organ. The dermatologic toxicities are observed in nearly half of the patients treated with ICIs, mainly in the form of maculopapular rash and pruritus. In the majority of cases, these cutaneous irAEs are self-limiting and manageable, and continuation of the ICIs is possible. This review provides an overview of variable ICI-mediated dermatologic reactions and describes the clinical and histopathologic presentation. Early and accurate diagnosis, recognition of severe toxicities, and appropriate management are key goals to achieve the most favorable outcomes and quality of life in cancer patients.
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Antineoplásicos Inmunológicos , Neoplasias , Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/tratamiento farmacológico , Calidad de VidaRESUMEN
BACKGROUND: High body mass index (BMI) has been reported to be associated with the efficacy of immune checkpoint inhibitors in patients with advanced non-small cell lung cancer (NSCLC), but the association between BMI and efficacy of anti-PD-1 inhibitors remains controversial. The present study investigated this association in patients with advanced NSCLC. METHODS: We retrospectively reviewed patients with advanced NSCLC who received PD-1 inhibitors at the National Cancer Center Hospital between January 2016 and December 2018. The efficacy of PD-1 inhibitors (progression-free survival [PFS], overall survival [OS], and response rate) was compared between overweight (BMI ≥25 kg/m2) and non-overweight (BMI <25 kg/m2) groups. Cohort 1 included patients with high PD-L1 expression who were treated with pembrolizumab as first-line therapy; Cohort 2 included patients treated with nivolumab/pembrolizumab as second- or later-line treatment. RESULTS: A total of 324 patients were included in this study and the median BMI (IQR) was 21.4 (19.5-23.6) kg/m2. Of the 324 patients, 279 (86.1%) and 45 (13.9%) were in the non-overweight and overweight groups, respectively. No significant differences in objective response rate (ORR), PFS, or OS were found between overweight and non-overweight patients overall (n = 324; overweight vs. non-overweight: ORR, 28.9% vs. 31.9%, respectively [p = 0.68]; PFS, 7.6 vs. 5.8 months, respectively [p = 0.43]; and OS, 17.6 vs. 15.3 months, respectively [p = 0.90]), or between overweight and non-overweight patients in Cohorts 1 and 2. CONCLUSIONS: No significant differences in the efficacy of PD-1 inhibitors were observed between overweight and non-overweight patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Índice de Masa Corporal , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
Nearly half of all metastatic melanoma patients possess the BRAF V600 mutation. Several therapies are approved for advanced stage melanoma, but it is unclear if there is a differential outcome to various immunotherapy regimens based on BRAF mutation status. We retrospectively analyzed a cohort of metastatic or unresectable melanoma patients who were treated with combination ipilimumab/nivolumab (ipi/nivo) or anti-PD-1 monotherapy, nivolumab, or pembrolizumab, as first-line treatment. 235 previously untreated patients were identified in our study. Our univariate analysis showed no statistical difference in progression-free survival (PFS) or overall survival (OS) with ipi/nivo versus anti-PD-1 monotherapy in the BRAF V600 mutant cohort, but there was improved PFS [HR: 0.48, 95% CI, 0.28-0.80] and OS [HR: 0.50, 95% CI, 0.26-0.96] with ipi/nivo compared to anti-PD-1 monotherapy in the BRAF WT group. After adjusting for known prognostic variables in our multivariable analysis, the BRAF WT cohort continued to show PFS and OS benefit with ipi/nivo compared to anti-PD-1 monotherapy. Our single-institution analysis suggests ipi/nivo should be considered over anti-PD-1 monotherapy as the initial immunotherapy regimen for metastatic melanoma patients regardless of BRAF mutation status, but possibly with greater benefit in BRAF WT.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/genética , Melanoma/mortalidad , Mutación , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Proteínas Proto-Oncogénicas B-raf/genética , Anticuerpos Monoclonales Humanizados/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Ipilimumab/administración & dosificación , Masculino , Melanoma/tratamiento farmacológico , Melanoma/genética , Melanoma/patología , Persona de Mediana Edad , Nivolumab/administración & dosificación , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIM: We assessed the efficacy of immune checkpoint inhibitors (ICIs) in older patients because of the limited information regarding these patients. PATIENTS AND METHODS: We retrospectively analyzed 66 consecutive patients ≥70 years old with advanced non-small cell lung cancer (NSCLC). A total of 31 patients received ICIs (ICIs group) and 35 patients received only cytotoxic regimens (No ICIs group). RESULTS: Patients with squamous cell carcinoma who received ICIs had better overall survival (OS) than those who did not (9.7 versus 4.7 months, p=0.027). In multivariate analysis, treatment with ICIs [hazard ratio (HR)=0.54, 95% confidence interval (CI)=0.30-0.98, p=0.044], good performance status (HR=0.30, 95%CI=0.16-0.57, p=0.0003), and histology other than squamous cell carcinoma (HR=0.41, 95%CI=0.19-0.83, p=0.014) were significantly favorable factors for OS. CONCLUSION: ICIs may be effective for older patients with NSCLC, especially squamous cell carcinoma patients.
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Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We present an illustrative case of a 62-year-old woman with small cell lung cancer who developed progressive worsening of pre-existing anti-Hu antibody associated sensory neuronopathy after treatment with programmed cell death-1 (PD-1) inhibitor, nivolumab. We review the literature and identify 6 reported cases to understand the clinical outcomes of patients with anti-Hu paraneoplastic neurologic syndrome (PNS) treated with anti-PD-1 treatment. The PNS clinical spectrum comprised of encephalitis, a combination of sensory neuronopathy and anti-NMDAR encephalitis, isolated sensory neuronopathy, and encephalomyelitis. Immune checkpoint inhibitor have the potential to worsen pre-existing anti-Hu PNS and may promote the development of anti-Hu PNS.
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Anticuerpos Antinucleares/sangre , Antineoplásicos Inmunológicos/efectos adversos , Autoantígenos/inmunología , Proteínas ELAV/inmunología , Nivolumab/efectos adversos , Síndromes Paraneoplásicos del Sistema Nervioso/etiología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Anticuerpos Antinucleares/inmunología , Anticuerpos Antineoplásicos , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carcinoma de Células Pequeñas/complicaciones , Carcinoma de Células Pequeñas/tratamiento farmacológico , Carcinoma de Células Pequeñas/inmunología , Carcinoma de Células Pequeñas/secundario , Neoplasias Cerebelosas/complicaciones , Neoplasias Cerebelosas/tratamiento farmacológico , Neoplasias Cerebelosas/inmunología , Neoplasias Cerebelosas/secundario , Terapia Combinada , Progresión de la Enfermedad , Etopósido/administración & dosificación , Femenino , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/radioterapia , Persona de Mediana Edad , Nivolumab/uso terapéutico , Síndromes Paraneoplásicos del Sistema Nervioso/inducido químicamente , Síndromes Paraneoplásicos del Sistema Nervioso/inmunología , Radioterapia Adyuvante , Resultado del TratamientoRESUMEN
Advanced squamous cell lung carcinoma in elderly patients has a limited chance of cure with first, second line chemotherapy and radiotherapy. Radiotherapy in advanced non-small-cell lung cancer can be used with curative intent for localized or oligometastatic disease using standard or altered fractionations. Current evidence indicates that radiotherapy via diverse cascade mechanisms is able to invoke both local and systemic immunoresponses promoting tumor cell death through an in situ vaccination effect. Moreover, the advancement in immunotherapies is changing the scenario. The combination of radiotherapy and immunotherapy could be a crucial strategy to overcome cancer immunoresistance and improve patient survival, as we found in this case report of an elderly, refractory advanced lung cancer patient who has achieved complete remission after this therapeutic combination.
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Treatment options for patients with platinum-refractory, recurrent, metastatic head and neck squamous cell carcinoma (HNSCC) are limited, and prognosis is poor. Nivolumab (Opdivo) has been approved by the US Food and Drug Administration (FDA) for the treatment of patients with recurrent or metastatic HNSCC who have disease progression on or after platinum-based therapy. Recently, in patients with metastatic malignant melanoma a significant improvement of outcome and response was achieved with the combination of ipilimumab (CTLA4 antibody) and the programmed death (PD)-1 inhibitor nivolumab compared with monotherapy. Based on these results, the combination of nivolumab and ipilimumab has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma. So far, there have been no data concerning the combination of nivolumab and ipilimumab in squamous cell head and neck cancer. We here present the case of a 46-year-old male with refractory squamous cell head and neck cancer, who was successfully treated with the PD-1 inhibitor nivolumab in combination with the anti-CTLA4 antibody ipilimumab.
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INTRODUCTION: Nivolumab is a recombinant, humanized monoclonal antibody that binds PD-1. The binding of PD-1 with PD-L1, expressed on antigen-presenting cells and tumor cells, suppresses the ability of T-lymphocytes to recognize and destroy tumor cells. Nivolumab reverts this inhibitory signal and has led to a significant prolongation of overall survival in patients with metastatic renal cell carcinoma (RCC). AREAS COVERED: The rationale for immunotherapy in metastatic RCC, key immune checkpoint pathways, nivolumab pharmacodynamics, results from the main clinical trials, and predictors of response are discussed. EXPERT OPINION: Nivolumab demonstrated a statistically significant advantage over everolimus in overall survival in metastatic RCC patients after first-line antiangiogenic therapy. Nevertheless, a number of issues remain to be resolved regarding the use of this drug in RCC. It is now imperative to identify which patients can benefit most from immunotherapy and studies are ongoing to define its role in other settings and/or in combinations with antiCTLA4 or antiangiogenic drugs.