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Spiradenocarcinomas are rare malignant skin adnexal tumors. We describe a novel case of a patient with an aggressive CDKN2A-mutated spiradenocarcinoma who responded to a CDK4/6 inhibitor. This case highlights the unique nature of spiradenocarcinomas as well as the potential benefit of targeted therapy.
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Inibidor p16 de Quinase Dependente de Ciclina , Mutação , Humanos , Inibidor p16 de Quinase Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/genética , Feminino , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Pessoa de Meia-Idade , Adenocarcinoma/genética , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Quinase 6 Dependente de Ciclina/genética , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Masculino , Piridinas/uso terapêutico , Neoplasias das Glândulas Sudoríparas/genética , Neoplasias das Glândulas Sudoríparas/patologia , Neoplasias das Glândulas Sudoríparas/tratamento farmacológico , Piperazinas/uso terapêuticoRESUMO
BACKGROUND: There are limited to no data regarding the use of immune checkpoint inhibitors (ICIs) in patients who have preexisting organ dysfunction because these patients are frequently excluded from clinical trials. The authors' objective was to evaluate the effects of ICIs in patients with chronic kidney disease (CKD), cirrhosis, chronic obstructive pulmonary disease (COPD), and congestive heart failure (CHF). METHODS: Data were obtained retrospectively for patients older than 18 years with solid organ malignancies who received at least one dose of an ICI between January 1, 2015, and January 1, 2021, and had either CKD (n = 90), cirrhosis (n = 20), COPD (n = 142), or CHF (n = 82) before ICI initiation at the authors' institution. Descriptive statistics were used to summarize patient characteristics, treatment characteristics, immune-related adverse events (IrAEs), and outcomes. An independent samples t-test or the Wilcoxon rank-sum test was used to assess differences in continuous variables; the χ2 test or the Fisher exact test was used to assess differences in categorical variables between patients with and without IrAEs. Progression-free survival (PFS) was assessed using Kaplan-Meier curves, and the log-rank test was used to assess differences in PFS. RESULTS: In all four cohorts, there were no statistically significant differences in patient characteristics, treatment characteristics, or outcomes, such as the number of hospitalizations and PFS, among those who experienced IrAEs compared with those who did not. In the CKD cohort, patients with IrAEs were significantly less likely to die than those without IrAEs (52% vs. 81% [p = .009] for all patients; 53% vs. 83% [p = .008] for patients with stage II/III disease who received no definitive local treatment and patients with stage IV disease); this difference was not observed in the cirrhosis, COPD, or CHF cohorts. There was no statistically significant difference in the number of heart failure and COPD exacerbations during the receipt of ICIs in the CHF and COPD cohorts, respectively. The incidence and time to onset of IrAEs in this study appeared to be similar to those reported previously in clinical trials that excluded patients with significant comorbidities. CONCLUSIONS: The current results demonstrate that ICIs are well tolerated by patients who have preexisting organ dysfunction.
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Doença Pulmonar Obstrutiva Crônica , Insuficiência Renal Crônica , Humanos , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/efeitos adversos , Insuficiência de Múltiplos Órgãos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
The aim of the NCCN Guidelines for Management of Immunotherapy-Related Toxicities is to provide guidance on the management of immune-related adverse events resulting from cancer immunotherapy. The NCCN Management of Immunotherapy-Related Toxicities Panel is an interdisciplinary group of representatives from NCCN Member Institutions, consisting of medical and hematologic oncologists with expertise across a wide range of disease sites, and experts from the areas of dermatology, gastroenterology, endocrinology, neurooncology, nephrology, cardio-oncology, ophthalmology, pulmonary medicine, and oncology nursing. The content featured in this issue is an excerpt of the recommendations for managing toxicities related to CAR T-cell therapies and a review of existing evidence. For the full version of the NCCN Guidelines, including recommendations for managing toxicities related to immune checkpoint inhibitors, visit NCCN.org.
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Oncologia , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico , Fatores Imunológicos/uso terapêutico , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: The advent of targeted therapies and immunomodulatory agents has revolutionized the management of advanced cutaneous malignant melanoma (MMel) by prolonging overall survival. This study evaluated the therapeutic and survival disparities among patients with advanced MMel based on hospital volume using the National Cancer Database (NCDB). METHODS: A retrospective analysis using regression models and Kaplan-Meier estimates was performed from the data obtained from the NCDB on patients with MMel diagnosed in 2004 through 2015. RESULTS: A total of 40,676 patients with MMel were treated at 1,260 facilities. Multivariable analysis showed that facility volume was an independent predictor of overall survival (P<.0001). Compared with patients treated at high-volume facilities (tertile 3 [T3]), those with stage III disease (n=27,528) treated at intermediate- and low-volume facilities (T2 and T1, respectively) had a significantly higher risk of death (T2 hazard ratio [HR], 1.15; 95% CI, 1.09-1.20; T1 HR, 1.23; 95% CI, 1.17-1.29). Compared with patients treated at T3 facilities, those with stage IV disease (n=13,148) treated at lower-tertile facilities had a significantly higher risk of death (T2 HR, 1.16; 95% CI, 1.10-1.21; T1 HR, 1.29; 95% CI, 1.23-1.36). Further, patients with stage IV disease treated at T3 facilities (vs T1 facilities) were more likely to receive chemotherapy (38% vs 28%) and immunotherapy (23% vs 10%) (P<.0001). CONCLUSIONS: Patients with advanced-stage MMel treated at high-volume facilities had significantly improved survival and were more likely to receive chemotherapy and immunotherapy.
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Hospitais/estatística & dados numéricos , Melanoma/terapia , Neoplasias Cutâneas/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Cutâneas/mortalidade , Adulto Jovem , Melanoma Maligno CutâneoRESUMO
Patients who are able to care for themselves but are unable to perform most work-related activities are considered to have a poor performance status (PS). Individuals who fulfill these criteria constitute a significant proportion of all patients with lung cancer. Patients with lung cancer and a poor PS, irrespective of age, have an increased incidence of adverse effects with therapy and poorer outcomes. Thus, although these individuals must be treated differently, data on optimal approaches for these patients are lacking, because this cohort is underrepresented in conventional clinical trials due to enrollment restrictions. This article presents the available evidence on the treatment of this group of patients with lung cancer. Although patients with PS 2 have worse overall outcomes than those with good PS, a selected proportion may still benefit from standard therapy. Further trials are needed to identify optimal strategies to treat this group of patients with lung cancer.
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Atividades Cotidianas , Carcinoma Pulmonar de Células não Pequenas/psicologia , Neoplasias Pulmonares/psicologia , Qualidade de Vida , Análise e Desempenho de Tarefas , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Terapia Combinada , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Testes de Função Respiratória , Resultado do TratamentoRESUMO
Background: Recent advancements in the management of non-small cell lung cancer (NSCLC) have confirmed the utility of adding adjuvant immunotherapy to concurrent chemoradiotherapy in stage III disease but intrathoracic progression remains at high rate. Additional studies have sought to investigate the synergistic relationship of immunotherapy and radiation therapy (RT). The goal of this study is to evaluate the safety and efficacy of combining consolidative hypofractionated radiation therapy (hfRT) using stereotactic body radiotherapy (SBRT) technique for boosting the residual primary lung cancer with adjuvant anti-programmed death-ligand 1 (PD-L1) therapy concurrently after completion of definitive chemoradiation therapy (dCRT) in the rates of tumor control locoregionally and distantly. Methods: Eligible subjects with stage III NSCLC must have gross residual tumor that is smaller than 5.0 cm in maximal dimension following dCRT. Consolidative hfRT will be delivered 1 to 2 months after finishing dCRT and concurrently with adjuvant anti-PD-L1 therapy using durvalumab. Consolidative hfRT will start from 6.5 Gy ×2 fractions and dose escalate to 10 Gy ×2 fractions in a 3+3 design. At the final determined consolidative hfRT dose level, a total of 32 subjects with pathologically documented stage III NSCLC treated with two or more cycles of platinum-based doublet chemotherapy concurrently with RT will be enrolled for data analyses. Discussion: We hypothesize that the use of consolidative hfRT directed to the residual primary lung tumor in combination with adjuvant anti-PD-L1 therapy will provide additional immunostimulation and therefore improved locoregional and distant control when compared to either modality used independently. Registration: Clinicaltrials.gov: NCT04748419.
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BACKGROUND/AIM: The PACIFIC trial demonstrated improved survival in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with durvalumab following definitive concurrent chemoradiotherapy (CRT). This study sought to explore real-world outcomes with durvalumab consolidation therapy at our institution. PATIENTS AND METHODS: We retrospectively identified patients diagnosed with stage III NSCLC at our institution from January 2012 to January 2022. We created two cohorts: one who received durvalumab following definitive CRT and a historical one who did not. Primary outcomes of interest included median progression-free survival (PFS) and overall survival (OS). Additionally, we performed subgroup analysis on the durvalumab cohort to explore the associations between survival and time to durvalumab initiation, PD-L1 expression, and neutrophil-to-lymphocyte ratio (NLR). RESULTS: We identified 79 patients with locally advanced NSCLC who were not surgical candidates. Patients treated with durvalumab (n=44) had significantly improved survival compared to the historical cohort (n=35) including a median PFS of 17.4 months versus 8.0 months (p=0.0019) and a median OS of 37.0 months versus 17.0 months (log-rank p-value=0.07, Wilcoxon p-value=0.02). Within the durvalumab group, outcomes did not significantly differ between those who initiated therapy before or after 42 days of finishing CRT, between various PD-L1 expression levels, or between high or low NLR. CONCLUSION: Patients who received durvalumab as consolidation therapy following definitive CRT demonstrated significantly improved survival compared to a historical cohort who did not receive durvalumab. Furthermore, durvalumab appears to benefit patients regardless of time to initiation, PD-L1 expression, or NLR.
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Anticorpos Monoclonais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Estudos RetrospectivosRESUMO
The objective of the study is to compare sentinel lymph node (SLN) identification rates and performance characteristics of lymphoscintigraphy using 99mTc-sulfur colloid (SC) and 99mTc-tilmanocept (TL) for head and neck cutaneous melanoma. This study is a retrospective study, conducted at a single, tertiary care cancer center. Patients underwent sentinel lymph node biopsy (SLNB) for head and neck cutaneous melanoma, using SC or TL, between October 2014 and February 2019. Differences in SLN identification rates and performance characteristics between the groups were examined using the Mann-Whitney, or Fisher's exact test. Sixty patients underwent SLNB, of which 19 employed TL. There were no significant differences between SC vs. TL in operative duration (116 vs. 127 min, P = 0.97), radiation dose (530 vs. 547 µCi, P = 0.27), median number of SLNs removed (3 vs. 2, P = 0.32), or median follow-up (46.3 vs. 38.4 months, P = 0.11). The rates of positive SLNs (17% vs. 37%, P = 0.11), intraoperative non-localization (12% vs. 16%, P = 0.70), and false-negative SLNB (5% each, P = 1.00) were not significantly different between groups. In patients with head and neck melanoma undergoing SLNB, 99mTc-tilmanocept may not differ from 99mTc-sulfur colloid in identifying SLNs or other performance characteristics. The added expense related to 99mTc-tilmanocept and lack of favorable performance data should urge caution in its adoption and promote further examination of its value in similar patient cohorts.
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PURPOSE: Targeted Agent and Profiling Utilization Registry (TAPUR) is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results of a cohort of patients with soft tissue sarcoma with cyclin-dependent kinase 4 (CDK4) amplification treated with palbociclib are reported. METHODS: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0 to 2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16+ weeks duration (SD16+) according to RECIST v1.1. The DC rate was estimated with a 90% CI. Secondary end points included OR, progression-free survival (PFS), overall survival (OS), duration of response, duration of SD, and safety. RESULTS: Forty-two patients with CDK4 amplification were enrolled. One patient was not evaluable for efficacy. One patient with partial response and 18 with SD16+ were observed for DC and OR rates of 46% (90% CI, 36 to 100) and 2% (95% CI, <1 to 13), respectively. Median PFS was 16 weeks (95% CI, 9 to 28) and median OS was 69 weeks (95% CI, 31 to 111) for evaluable patients. Twenty patients had at least one grade 3 to 4 adverse event (AE) at least possibly related to palbociclib, including alanine aminotransferase increase, anemia, fatigue, hypophosphatemia, leukopenia, neutropenia, and thrombocytopenia. No serious AEs were reported. CONCLUSION: Palbociclib met prespecified criteria to declare a signal of antitumor activity in patients with sarcoma and CDK4 amplification.
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Quinase 4 Dependente de Ciclina , Piperazinas , Piridinas , Sistema de Registros , Sarcoma , Humanos , Quinase 4 Dependente de Ciclina/genética , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Piridinas/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Adulto , Idoso , Sarcoma/tratamento farmacológico , Sarcoma/genética , Amplificação de Genes , Adulto Jovem , Idoso de 80 Anos ou maisRESUMO
Immune checkpoint inhibitors (ICPis) have proven extremely efficacious in cancer therapy but also lead to a plethora of immune-related adverse events (irAEs). The endocrine irAEs are not only quite common but also may pose a challenge to the clinician while managing a patient with cancer treated with ICPis. The clinical features of endocrine dysfunction are usually nonspecific and may overlap with concurrent illnesses, underlying the importance of accurate hormone testing and efforts toward case-finding. The management of endocrine irAEs is unique in the focus being on hormone replacement rather than curtailing the autoimmune process. Although the management of thyroid irAEs appears straightforward, adrenal insufficiency and insulin-dependent diabetes can be life-threatening if not promptly recognized and treated. This clinical review synthesizes the studies to provide pearls and pitfalls in the evaluation and management of endocrine irAEs with specific reference to guidelines from oncologic societies.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Imunoterapia/efeitos adversos , Hormônios/uso terapêuticoRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with ATM mutations treated with nivolumab plus ipilimumab are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. Primary end point was disease control (DC), defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16 weeks duration (SD16+). Low-accruing histology-specific cohorts with ATM mutations treated with nivolumab plus ipilimumab were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated based on a one-sided exact binomial test with a null DC rate of 15% versus 35% (power = .84; α = .10). Secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of SD, and safety. RESULTS: Twenty-nine patients with 10 tumor types with ATM mutations were enrolled from January 2018 to May 2020. One patient was not evaluable for efficacy. One CR, three PR, and three SD16+ were observed for DC and OR rates of 24% (P = .13; one-sided 90% CI: 14 to 100) and 14% (95% CI: 4 to 32), respectively. The null hypothesis of 15% DC rate was not rejected. Eleven patients had one treatment-related grade 3 adverse event (AE) or serious AE. There were two treatment-related patient deaths including immune-related encephalitis and respiratory failure. CONCLUSION: Nivolumab plus ipilimumab did not meet prespecified criteria to declare a signal of activity in patients with solid tumors with ATM mutations.
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Antineoplásicos , Melanoma , Humanos , Nivolumabe/uso terapêutico , Ipilimumab/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Mutação , Proteínas Mutadas de Ataxia Telangiectasia/genéticaRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a pragmatic basket trial evaluating antitumor activity of approved targeted agents in patients with advanced cancers harboring potentially actionable genomic alterations. Data from cohorts of patients with high tumor mutational burden (HTMB, defined as ≥9 mutations per megabase) with advanced colorectal cancer (CRC) and other advanced cancers treated with pembrolizumab are reported. METHODS: Eligible patients were 18 years and older with measurable tumors and a lack of standard treatment options, an Eastern Cooperative Oncology Group performance status of 0-1, and adequate organ function. The primary end point was disease control (DC), defined as complete or partial response or stable disease (SD) of at least 16-weeks duration. For the CRC cohort, Simon's two-stage design with a null DC rate of 15% versus 35% (power = 0.85; α = .10) was used. Low accruing histology-specific cohorts were collapsed into one histology-pooled (HP) cohort. For the HP cohort, the null hypothesis of a DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was >15%. Secondary end points included objective response (OR), safety, progression-free survival, overall survival, duration of response, and duration of SD. RESULTS: Seventy-seven patients with HTMB with CRC (n = 28) or advanced cancers (n = 49) were treated with pembrolizumab. For the CRC cohort, the DC rate was 31% (P = .04) and the OR rate was 11%. For the HP cohort, the DC rate was 45% (one-sided 90% CI, 35 to 100) and the OR rate was 26%. The null hypothesis of a 15% DC rate was rejected for both cohorts. Twelve of 77 patients experienced treatment-related grade 3 adverse events (AEs) or serious AEs, including two deaths. CONCLUSION: Pembrolizumab demonstrated antitumor activity in pretreated patients with advanced cancers and HTMB.
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Antineoplásicos , Neoplasias Colorretais , Humanos , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genéticaRESUMO
Adjuvant chemotherapy improves overall survival (OS) following stereotactic body radiotherapy (SBRT) in patients with early stage non-small cell lung cancer and tumors ≥four cm. Here, we aim to evaluate its role following SBRT in older patients. Patients >70 years diagnosed with clinical stages I-II NSCLC, (N0 disease), who received SBRT, were identified using the National Cancer Database (n = 7042). The Kaplan-Meier method was used to estimate OS, and the log-rank test was used to compare distributions by treatment strategy overall and within clinical stages I and II. There were 3533 female patients (50.2%), and 6074 (86.3%) had stage I disease. Among stage I patients, 643 (10.6%) received adjuvant chemotherapy, compared to 372 stage II patients (38.4%). Median OS was better with SBRT in patients with stage I disease (25.4 vs. 20.3 months; p < .001); while patients with stage II NSCLC had better OS with SBRT + chemotherapy (20.2 vs. 14.2 months; p < .001). On multivariate analysis, patients with stage I NSCLC who received SBRT alone had better overall survival (HR: 0.79; 95% CI, 0.73, 0.87). SBRT alone was associated with an increased risk of death in patients with stage II disease (HR: 1.34; 95% CI, 1.15, 1.55). Patients with tumors ≥4 cm had better OS with SBRT + chemotherapy (18.5 vs. 15.5 months; p = .003), while patients with tumors <4 cm did better with SBRT (median OS of 24.1 vs. 20.3 months; p < .001). In >70 years old patients with tumors ≥4 cm, adjuvant chemotherapy following SBRT was associated with improved OS.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Resultado do TratamentoRESUMO
BACKGROUND: Relapsed/refractory small cell lung cancer (SCLC) has a poor prognosis, with no good options. We evaluated a novel combination of topotecan and doxorubicin, providing sequential topoisomerase I and II inhibition, in this setting. MATERIALS AND METHODS: Adult patients (>19 years) with relapsed/refractory SCLC, who had received at least one prior chemotherapy regimen were eligible. Patients received escalating doses of oral topotecan on days 1-5 of each three week cycle (maximum - 5 cycles). The dosing cohorts were: 0.85â¯mg/m2, 1.05â¯mg/m2, 1.35â¯mg/m2, 1.65â¯mg/m2 and 2.30â¯mg/m2. All patients received weekly doxorubicin 20â¯mg/m2 intravenously starting day 6 of the first cycle and continued weekly for a maximum of 15 weeks. In the absence of pre-specified dose limiting toxicities (DLT), patients were enrolled serially to escalated dose level cohorts. RESULTS: Twenty-two patients were enrolled, of which 20 were evaluable. Median age was 61 years; 74% were male and 95% were Caucasian. Hematologic side effects were the most common adverse events. There were no therapy-related Grade 5 toxicities. Incidence of DLT based on cohorts were: DL2: 1/6 (Grade 4 thrombocytopenia), DL3: 1/6 (AST elevation) and DL4: 2/4 (Grade 4 thrombocytopenia). Response rate was 20% (4/20) and disease control rate (SDâ¯+â¯PR) was 36%. The median progression free and overall survival were 3.6 months and 6 months, respectively. CONCLUSIONS: The combination of topotecan and doxorubicin was safe and effective in relapsed/refractory SCLC. The maximum tolerated dose of oral topotecan was 1.35â¯mg/m2 when given concurrently with weekly doxorubicin.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Topotecan/efeitos adversos , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Aspartato Aminotransferases/sangue , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Índice de Gravidade de Doença , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Trombocitopenia/sangue , Trombocitopenia/induzido quimicamente , Trombocitopenia/diagnóstico , Trombocitopenia/epidemiologia , Topotecan/administração & dosagemRESUMO
PURPOSE: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS: Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon's two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION: Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.
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INTRODUCTION: Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting. METHODS: Patients (≥18 years) diagnosed with clinical stages I-II NSCLC from 2004 to 2013 were identified using the National Cancer Database (n = 11,836). The Kaplan-Meier method was used to estimate overall survival (OS) distributions and the log-rank test was used to compare distributions by treatment strategy. Clinical stages I and II were subdivided according to the TNM staging and log-rank tests was used to compare survival distributions by treatment strategy within each subgroup. RESULTS: In patients with T2bN0, median OS in the SBRT alone and SBRT plus adjuvant chemotherapy groups were 16.5 months versus 24.2 months, respectively (95% confidence interval [CI]: 14.1-20.1 months and 18.8-33.3 months, respectively; p < .001); whereas for T3N0, median OS times were 13 months and 20.1 months, respectively (95% CI: 11.7-14.5 mohths and 17.7-21.9 months, respectively; p < .001). For tumors 4 cm or larger and node-negative disease, median OS was 15.9 months in the SBRT-alone group, and 19 months in the SBRT-plus-chemotherapy group (95% CI: 15.1-16.8 months and 17.9-20.8 months, respectively; p < .001). For patients with tumors less than 4 cm and node-negative disease, the median OS was 28.5 months in the SBRT-alone group and 24.3 months in the SBRT-plus-chemotherapy group (95% CI: 27.4-29.4 months and 22.8-26.1 months, respectively; p < .001). CONCLUSIONS: SBRT followed by adjuvant chemotherapy was associated with improved OS in comparison with SBRT alone in patients with T greater than or equal to 4 cm, similar to that seen after surgery.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Quimioterapia Adjuvante/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Radiocirurgia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
OBJECTIVE: Platinum-based doublet chemotherapy is the standard for most patients with advanced non-small cell lung cancer (NSCLC). Toxicity concerns limit chemotherapy for patients over 70years. Vinorelbine and paclitaxel are effective as single agents in advanced NSCLC. This phase II study evaluates safety and efficacy of a combination of these two agents in patients >70years with advanced NSCLC. MATERIALS AND METHODS: Patients with treatment naïve metastatic NSCLC received two cycles comprising 6 weekly doses of vinorelbine and paclitaxel, with restaging scans at week 8. Patients with radiographic progression came off study. The estimated sample size was 29. Toxicity analyses were conducted after 10 patients and again after 19 patients were enrolled. Outcomes were safety and efficacy, progression free (PFS) and overall survival (OS) and quality of life (QOL). RESULTS: The study closed at second interim analysis as 6/19 patients had ≥grade 4 non-hematologic toxicity (respiratory failure, sepsis, ischemic encephalopathy, pneumonia, hypoxemia, cardiopulmonary arrest, neutropenic fever, death). Of the 16 evaluable patients, 7 completed the study. Disease control rate (partial response+stable disease) was 47% (n=9); 37% (n=7) progressed. No complete responses were seen. Median PFS was 3.5months (95% CI: 1.4, 5.5) and OS 7.8months (95% CI: 1.9, 13.6). QOL did not change compared to baseline, at week 9, but increased at week 17. CONCLUSIONS: Although the combination met its response end points, increased toxicity makes this combination unsuitable for older patients. While QOL improved over the study, the small sample hinders interpretation.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Anemia/induzido quimicamente , Isquemia Encefálica/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Neutropenia Febril Induzida por Quimioterapia/etiologia , Intervalo Livre de Doença , Término Precoce de Ensaios Clínicos , Feminino , Parada Cardíaca/induzido quimicamente , Humanos , Hipóxia/induzido quimicamente , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfopenia/induzido quimicamente , Masculino , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Pneumonia/induzido quimicamente , Qualidade de Vida , Insuficiência Respiratória/induzido quimicamente , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , VinorelbinaRESUMO
INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancers (NSCLC) may be more common in patients with brain metastases. Previous studies, however, did not adjust for effects of confounding variables. METHODS: This retrospective study included 1,522 consecutive patients with NSCLC, whose tumors were diagnosed and tested for EGFR mutations at the University of Nebraska Medical Center (Omaha, NE) and Tata Memorial Hospital (Mumbai, India). Multivariate logistic regression was used to identify any association between EGFR status and clinical factors. RESULTS: EGFR mutations were more common in females than males (38.7% v 24.8%), Asians than whites (31.3% v 13.4%), nonsmokers than smokers (40.2% v 14.6%), alcohol nonconsumers than users (32.4% v 15.8%), adenocarcinoma than other histology types (32.7% v 10.3%), and patients with brain metastases than extracranial or no metastases (39.4% v 29.8% v 15.1%; P < .001 for all comparisons). There was a higher likelihood of an EGFR mutation among patients with brain metastases (odds ratio, 1.8; P < .001). The median overall survival (OS) was 19.8 months. Patients with brain metastases had a shorter median OS (15 v 20.6 months; P = .02). However, in the cohort of EGFR mutation-positive patients, there was no difference in median OS between patients with and without brain metastases (20.8 v 25.1 months; P = .11). CONCLUSION: There is a nearly two-fold higher incidence of EGFR mutations in NSCLC among patients with brain metastases at diagnosis. EGFR mutations did not predict for outcomes from brain metastases.
RESUMO
Small cell lung cancer (SCLC) often presents with either regional or systemic metastases, but approximately 4% of patients present with a solitary pulmonary nodule. Surgical resection can be an option for these patients and is endorsed by the National Comprehensive Cancer Network (NCCN) guidelines. There are no prospective randomized clinical trials evaluating the role of adjuvant systemic therapy in these resected SCLC patients. A recent National Cancer Database analysis found that the receipt of adjuvant chemotherapy alone [hazard ratio (HR), 0.78; 95% CI, 0.63-0.95] or with brain radiation (HR, 0.52; 95% CI, 0.36-0.75) was associated with significantly improved survival as compared to surgery alone. As it is unlikely that a randomized prospective clinical trial addressing this question will be completed, these data should assist with decision making in these patients.
RESUMO
BACKGROUND: The median age at diagnosis of lung cancer is 70 years. However, the evidence guiding the management of octogenarians and older patients with non-small-cell lung cancer (NSCLC), is based on data derived from younger patients and may not be appropriate. METHODS: Patients ≥ 80 years diagnosed with clinical stages I and II NSCLC, between 1988 and 2007, were identified from the SEER database. Patients were classified according to treatments received: no treatment, surgery only, radiation only, and surgery + radiation. Factors associated with survival were assessed using the Cox proportional hazards model. RESULTS: There were 1338 cases of early stage NSCLC in octogenarians. Surgery was the most common treatment modality. The median overall survival was 3.8 years for patients who had surgery, compared with 1.6 years, 1.6 years, and 0.9 years for those who received surgery + radiation, radiation alone, and no treatment, respectively (P < .0001). Factors significantly associated with worse overall survival following surgery included increasing age (hazard ratio [HR], 1.08; P = .0005), male gender (HR, 1.33; P = .01), stage II (HR, 2.21; P < .0001), and squamous histology (HR, 1.36; P = .01). CONCLUSION: Surgical resection is associated with long-term survival outcomes in a substantial proportion of octogenarian and older patients with early stage lung cancer and should not be withheld on the basis of age alone.