RESUMO
PURPOSE: Lenvatinib, a potent multi-kinase inhibitor, improves progression-free survival (PFS) in patients with radioiodine (RAI)-refractory differentiated thyroid cancer (DTC); however, most patients experience disease progression, warranting further therapy. We evaluated the efficacy and safety of combination lenvatinib plus pembrolizumab (LP) in these patients. PATIENTS AND METHODS: We enrolled patients with progressive, RAI-refractory DTC that were either naïve to multi-kinase inhibitors (cohort 1) or who had progressed on lenvatinib (cohort 2). Patients received oral lenvatinib daily (cohort 1, 20 mg; cohort 2, dose at progression ) and intravenous pembrolizumab (200 mg) every 21 days. RESULTS: 30 and 27 patients were enrolled in cohort 1 and 2, respectively. Adverse events were consistent with those observed in other cancers. In cohort 1, the confirmed overall response rate (ORR) was 65.5%. There were no complete responses (CR, primary endpoint). The 12 and 18-month PFS were 72.0% and 58.0%, respectively, and median PFS was 26.8 months. In cohort 2, the confirmed ORR was 16% (primary endpoint), and median PFS was 10.0 months (95% CI; 7.0-17.9 months). Tumor histology, driver mutations, and immune-related biomarkers, including PD-L1 expression, thyroid-specific antibody levels, and CD8+ T cell tumor infiltrate, did not correlate with response to therapy. Increased baseline peripheral blood monocytes and neutrophil to lymphocyte ratio were associated with a worse PFS in cohort 1. CONCLUSIONS: Combination lenvatinib plus pembrolizumab may enhance the durability of lenvatinib monotherapy in lenvatinib-naïve patients. Furthermore, the addition of pembrolizumab may be a viable salvage therapy for patients who have progressed on lenvatinib.
RESUMO
RAF inhibitors have transformed treatment for BRAF V600-mutant cancer patients, but clinical benefit is limited by adaptive induction of ERK signaling, genetic alterations that induce BRAF V600 dimerization, and poor brain penetration. Next-generation pan-RAF dimer inhibitors are limited by narrow therapeutic index. PF-07799933 (ARRY-440) is a brain-penetrant, selective, pan-mutant BRAF inhibitor. PF-07799933 inhibited signaling in vitro, disrupted endogenous mutant-BRAF:wild-type-CRAF dimers, and spared wild-type ERK signaling. PF-07799933 ± binimetinib inhibited growth of mouse xenograft tumors driven by mutant BRAF that functions as dimers and by BRAF V600E with acquired resistance to current RAF inhibitors. We treated patients with treatment-refractory BRAF-mutant solid tumors in a first-in-human clinical trial (NCT05355701) that utilized a novel, flexible, pharmacokinetics-informed dose escalation design that allowed rapid achievement of PF-07799933 efficacious concentrations. PF-07799933 ± binimetinib was well-tolerated and resulted in multiple confirmed responses, systemically and in the brain, in BRAF-mutant cancer patients refractory to approved RAF inhibitors.
RESUMO
PURPOSE: To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis and cannabinoids, including synthetic cannabinoids and herbal cannabis derivatives; single, purified cannabinoids; combinations of cannabis ingredients; and full-spectrum cannabis. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and cohort studies on the efficacy and safety of cannabis and cannabinoids when used by adults with cancer. Outcomes of interest included antineoplastic effects, cancer treatment toxicity, symptoms, and quality of life. PubMed and the Cochrane Library were searched from database inception to January 27, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS: The evidence base consisted of 13 systematic reviews and five additional primary studies (four RCTs and one cohort study). The certainty of evidence for most outcomes was low or very low. RECOMMENDATIONS: Cannabis and/or cannabinoid access and use by adults with cancer has outpaced the science supporting their clinical use. This guideline provides strategies for open, nonjudgmental communication between clinicians and adults with cancer about the use of cannabis and/or cannabinoids. Clinicians should recommend against using cannabis or cannabinoids as a cancer-directed treatment unless within the context of a clinical trial. Cannabis and/or cannabinoids may improve refractory, chemotherapy-induced nausea and vomiting when added to guideline-concordant antiemetic regimens. Whether cannabis and/or cannabinoids can improve other supportive care outcomes remains uncertain. This guideline also highlights the critical need for more cannabis and/or cannabinoid research.Additional information is available at www.asco.org/supportive-care-guidelines.
Assuntos
Canabinoides , Maconha Medicinal , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Canabinoides/uso terapêutico , Canabinoides/efeitos adversos , Maconha Medicinal/uso terapêutico , Maconha Medicinal/efeitos adversos , AdultoRESUMO
WHAT IS THIS SUMMARY ABOUT?: This is a summary of a research study called ARROW, which tested a medicine called pralsetinib in patients with non-small cell lung cancer (NSCLC), thyroid cancer, and other advanced solid tumours caused by a change in a gene called RET. For the purposes of this summary, only patients with NSCLC with a change in RET called fusion (RET fusion+) are highlighted. WHAT WERE THE RESULTS?: In total, 281 patients with RET fusion+ NSCLC had taken part in this study across the USA, Europe, and Asia. Patients were asked to take four pills (adding up to 400 mg) of pralsetinib each day and were checked for any changes in their tumours, as well as for any side effects. After an average of 8 months of treatment with pralsetinib, 72% of previously untreated patients and 59% of patients who had previously received chemotherapy had considerable shrinkage of their tumours. Among 10 patients with tumours which had spread to the brain (all of whom had received previous treatments), 70% had their tumours shrink greatly in the brain after treatment with pralsetinib. On average, patients lived with little to no tumour growth for 16 months. In previously untreated patients, the most common severe side effects that were considered related to pralsetinib treatment were decreased white blood cells (neutrophils and lymphocytes), increased blood pressure, and an increase in a blood protein called creatine phosphokinase. In previously treated patients, the severe side effects were decreased white blood cells (neutrophils, lymphocytes, and leukocytes), increased blood pressure, and low levels of red blood cells. In both untreated and previously treated patients, the most common severe side effects that required hospital attention were lung inflammation/swelling causing shortness of breath (pneumonitis) and lung infection (pneumonia). WHAT DO THE RESULTS MEAN?: Overall, the ARROW study showed that pralsetinib was effective in shrinking tumours in patients with RET fusion+ NSCLC regardless of previous treatment history. The recorded side effects were expected in patients receiving this type of medicine. Clinical Trial Registration: NCT03037385 (ARROW) (ClinicalTrials.gov).
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Pirazóis , Piridinas , Proteínas Proto-Oncogênicas c-ret/genéticaRESUMO
Background: The optimal timing for initiating multi-kinase inhibitors (MKIs) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC) remains unclear. Thus, we evaluated the real-world practice patterns and outcomes in asymptomatic patients with progressive RAI-R DTC (≥1 lesion ≥1 cm in diameter) in the USA (US population) and outside the USA (non-US population). Methods: In this prospective, non-interventional, open-label study, eligible patients were chosen by treating physicians to receive MKI therapy (cohort 1) or undergo active surveillance (cohort 2) at study entry. Cohort 2 patients were allowed to transition to MKI therapy later. The primary endpoint was time to symptomatic progression (TTSP) from study entry. Data were compared descriptively. When endpoints were inestimable, 36-month rates were calculated. Results: Of the 647 patients, 478 underwent active surveillance (cohort 2) and 169 received MKI treatment (cohort 1). Patients underwent surveillance at a higher rate in the US (92.6%) vs the non-US (66.9%) populations. Half of US and non-US patients who qualified for MKI treatment had initial American Thyroid Association (ATA) low-to-intermediate-risk disease. In cohort 2, the 36-month TTSP rates from study entry were 65.6% and 66.5% in the US and non-US populations, respectively. Cohort 2 patients treated later demonstrated 36-month TTSP rates of 30.8% and 55.8% in the US and non-US populations, respectively. Conclusions: Active surveillance is a viable option for asymptomatic patients with progressive RAI-R DTC. However, early intervention with MKI therapy may be more suitable for others. Further research is needed to identify patients who are optimal for active surveillance. Registration: NCT02303444.
Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Resultado do Tratamento , Radioisótopos do Iodo/uso terapêutico , Estudos Prospectivos , Adenocarcinoma/induzido quimicamenteRESUMO
Background: Lenvatinib and sorafenib are standard of care first-line treatments for advanced, radioiodine-refractory (RAIR) differentiated thyroid cancer (DTC). However, most patients eventually become treatment-resistant and require additional therapies. The phase 3 COSMIC-311 study investigated cabozantinib in patients with RAIR DTC who progressed on lenvatinib, sorafenib, or both and showed that cabozantinib provided substantial clinical benefit. Presented in this study is an analysis of COSMIC-311 based on prior therapy and histology. Methods: Patients were randomized 2:1 (stratification: prior lenvatinib [yes/no]; age [≤65, >65 years]) to oral cabozantinib (60 mg tablet/day) or matched placebo. Eligible patients received 1-2 prior vascular endothelial growth factor receptor-targeting tyrosine kinase inhibitors for DTC (lenvatinib or sorafenib required), had a confirmed DTC diagnosis, and were refractory to or ineligible for radioiodine therapy. For this analysis, progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 by a blinded independent radiology committee were evaluated by prior therapy (lenvatinib only, sorafenib only, both) and histology (papillary, follicular, oncocytic, poorly differentiated). Results: Two hundred fifty-eight patients were randomized (170 cabozantinib/88 placebo) who previously received sorafenib only (n = 96), lenvatinib only (n = 102), or both (n = 60). The median follow-up was 10.1 months. The median PFS (months) with cabozantinib/placebo was 16.6/3.2 (sorafenib only: hazard ratio [HR] 0.13 [95% confidence interval, CI, 0.06-0.26]), 5.8/1.9 (lenvatinib only: HR 0.28 [95% CI 0.16-0.48]), and 7.6/1.9 (both: HR 0.27 [95% CI 0.13-0.54]). The ORR with cabozantinib/placebo was 21%/0% (sorafenib only), 4%/0% (lenvatinib only), and 8%/0% (both). Disease histology consisted of 150 papillary and 113 follicular, including 43 oncocytic and 36 poorly differentiated. The median PFS (months) with cabozantinib/placebo was 9.2/1.9 (papillary: HR 0.27 [95% CI 0.17-0.43]), 11.2/2.5 (follicular: HR 0.18 [95% CI 0.10-0.31]), 11.2/2.5 (oncocytic: HR 0.06 [95% CI 0.02-0.21]), and 7.4/1.8 (poorly differentiated: HR 0.18 [95% CI 0.08-0.43]). The ORR with cabozantinib/placebo was 15%/0% (papillary), 8%/0% (follicular), 11%/0% (oncocytic), and 9%/0% (poorly differentiated). Safety outcomes evaluated were consistent with those previously observed for the overall population. Conclusions: Results indicate that cabozantinib benefits patients with RAIR DTC, regardless of prior lenvatinib or sorafenib treatments or histology. Clinical Trial Registration Number: NCT03690388.
Assuntos
Adenocarcinoma , Anilidas , Antineoplásicos , Piridinas , Quinolinas , Neoplasias da Glândula Tireoide , Humanos , Idoso , Sorafenibe/uso terapêutico , Intervalo Livre de Progressão , Radioisótopos do Iodo/uso terapêutico , Fator A de Crescimento do Endotélio Vascular , Antineoplásicos/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/patologia , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
PURPOSE: This open-label, single-arm, phase II study evaluated the vascular endothelial growth factor receptor 2 (VEGFR2) tyrosine kinase inhibitor (TKI) rivoceranib in patients with recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC). PATIENTS AND METHODS: Eligible patients had confirmed disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) with ≥20% increase in radiologically or clinically measurable lesions or appearance of new lesions within the preceding 6 months. Patients received oral rivoceranib 700 mg once daily. Primary outcomes were objective response rate (ORR) by investigator review and by blinded independent review committee (BIRC). RESULTS: Eighty patients were enrolled and 72 were efficacy evaluable. Seventy-four patients had distant metastases and 49 received prior systemic treatment (14 received VEGFR TKIs). Per investigator and BIRC, respectively, ORR was 15.3% [95% confidence interval (95% CI), 7.9-25.7] and 9.7% (95% CI, 4.0-19.0); median duration of response was 14.9 months (95% CI, 4.9-17.3) and 7.2 months (95% CI, 3.5-8.4); and median progression-free survival was 9.0 months (95% CI, 7.3-11.5) and 9.0 months (95% CI, 7.7-11.5). Grade ≥3 treatment-related adverse events occurred in 56 patients (70.0%); the most common were hypertension (34, 42.5%) and stomatitis (6, 7.5%). Four grade 5 events occurred with one attributed to rivoceranib (epistaxis). Sixty-eight patients (85.0%) had ≥1 dose modifications and 16 patients (20.0%) discontinued rivoceranib for toxicity. CONCLUSIONS: In patients with progressing R/M ACC, rivoceranib demonstrated antitumor activity and a manageable safety profile consistent with other VEGFR TKIs.
Assuntos
Antineoplásicos , Carcinoma Adenoide Cístico , Humanos , Antineoplásicos/efeitos adversos , Carcinoma Adenoide Cístico/tratamento farmacológico , Carcinoma Adenoide Cístico/patologia , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologiaRESUMO
Salivary gland carcinomas (SGC) are a rare and variable group of head and neck cancers with historically poor response to cytotoxic chemotherapy and immunotherapy in the recurrent, advanced, and metastatic settings. In the last decade, a number of targetable molecular alterations have been identified in SGCs including HER2 upregulation, androgen receptor overexpression, Notch receptor activation, NTRK gene fusions, and RET alterations which have dramatically improved treatment outcomes in this disease. Here, we review the landscape of precision therapy in SGC including current options for systemic management, ongoing clinical trials, and promising future directions.
Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias das Glândulas Salivares , Humanos , Neoplasias das Glândulas Salivares/patologia , Imunoterapia , Fusão Gênica , Glândulas Salivares/patologiaRESUMO
BACKGROUND CONTEXT: Reimbursement has slowly transitioned from a fee-for-service model to a bundled payment model after introduction of the United States Centers for Medicare and Medicaid Services bundled payment program. To minimize healthcare costs, some surgeons are trying to minimize healthcare expenditures by transitioning appropriately selected lumbar decompression patients to outpatient procedure centers. PURPOSE: To prepare a risk stratification calculator based on machine learning algorithms to improve surgeon's preoperative predictive capability of determining whether a patient undergoing lumbar decompression will meet inpatient vs. outpatient criteria. Inpatient criteria was defined as any overnight hospital stay. STUDY DESIGN/SETTING: Retrospective single-institution cohort. PATIENT SAMPLE: A total of 1656 patients undergoing primary lumbar decompression. OUTCOME MEASURES: Postoperative outcomes analyzed for inclusion into the risk calculator included length of stay. METHODS: Patients were split 80-20 into a training model and a predictive model. This resulted in 1,325 patients in the training model and 331 into the predictive model. A logistic regression analysis ensured proper variable inclusion into the model. C-statistics were used to understand model effectiveness. An odds ratio and nomogram were created once the optimal model was identified. RESULTS: A total of 1,656 patients were included in our cohort with 1,078 dischared on day of surgery and 578 patients spending ≥ 1 midnight in the hospital. Our model determined older patients (OR=1.06, p<.001) with a higher BMI (OR=1.04, p<0.001), higher back pain (OR=1.06, p=.019), increasing American Society of Anesthesiologists (ASA) score (OR=1.39, p=.012), and patients with more levels decompressed (OR=3.66, p<0.001) all had increased risks of staying overnight. Patients who were female (OR=0.59, p=.009) and those with private insurance (OR=0.64, p=.023) were less likely to be admitted overnight. Further, weighted scores based on training data were then created and patients with a cumulative score over 118 points had a 82.9% likelihood of overnight. Analysis of the 331 patients in the test data demonstrated using a cut-off of 118 points accurately predicted 64.8% of patients meeting inpatient criteria compared to 23.0% meeting outpatient criteria (p<0.001). Area under the curve analysis showed a score greater than 118 predicted admission 81.4% of the time. The algorithm was incorporated into an open access digital application available here: https://rothmanstatisticscalculators.shinyapps.io/Inpatient_Calculator/?_ga=2.171493472.1789252330.1671633274-469992803.1671633274 CONCLUSIONS: Utilizing machine-learning algorithms we created a highly reliable predictive calculator to determine if patients undergoing outpatient lumbar decompression would require admission. Patients who were younger, had lower BMI, lower preoperative back pain, lower ASA score, less levels decompressed, private insurance, lived with someone at home, and with minimal comorbidities were ideal candidates for outpatient surgery.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Descompressão Cirúrgica , Vértebras Lombares , Pacientes Ambulatoriais , Idoso , Feminino , Humanos , Masculino , Procedimentos Cirúrgicos Ambulatórios/métodos , Vértebras Lombares/cirurgia , Medicare , Estudos Retrospectivos , Medição de Risco , Estados Unidos , Descompressão Cirúrgica/estatística & dados numéricosRESUMO
Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12â¯046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.
Assuntos
COVID-19 , Neoplasias , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Masculino , COVID-19/epidemiologia , SARS-CoV-2 , Estudos de Coortes , Estudos Retrospectivos , Teste para COVID-19 , Síndrome da Liberação de Citocina/etiologia , Terapia de Imunossupressão , Imunoterapia/efeitos adversos , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
Five-year survival for human papilloma virus-unrelated head and neck squamous cell carcinomas remain below 50%. We assessed the safety of administering combination hypofractionated stereotactic body radiation therapy with single-dose durvalumab (anti-PD-L1) neoadjuvantly (n = 21) ( NCT03635164 ). The primary endpoint of the study was safety, which was met. Secondary endpoints included radiographic, pathologic and objective response; locoregional control; progression-free survival; and overall survival. Among evaluable patients at an early median follow-up of 16 months (448 d or 64 weeks), overall survival was 80.1% with 95% confidence interval (95% CI) (62.0%, 100.0%), locoregional control and progression-free survival were 75.8% with 95% CI (57.5%, 99.8%), and major pathological response or complete response was 75% with 95% exact CI (51.6%, 100.0%). For patients treated with 24 Gy, 89% with 95% CI (57.1%, 100.0%) had MPR or CR. Using high-dimensional multi-omics and spatial data as well as biological correlatives, we show that responders had: (1) an increase in effector T cells; (2) a decrease in immunosuppressive cells; and (3) an increase in antigen presentation post-treatment.
Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Radiocirurgia , Humanos , Neoplasias de Cabeça e Pescoço/terapia , Terapia Neoadjuvante/efeitos adversos , Infecções por Papillomavirus/complicações , Radiocirurgia/efeitos adversos , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapiaRESUMO
Introduction: Compared to anterior cervical discectomy and fusion (ACDF), the motion preservation of cervical disc arthroplasty (CDA) provides an attractive alternative with similar short-term results. However, there is a paucity of the economics of performing CDA over ACDF. Study Design: This was retrospective study. Objective: The objective of this study is to evaluate relative-value-units (RVUs), operative time, and RVUs-per-minute between single-level ACDF and CDA. Secondary outcomes included 30-day readmission, reoperation, and morbidity. Methods: Adults who underwent ACDF or CDA in 2011-2019 National Surgical Quality Improvement Program database datasets. Multivariate quantile regression was utilized. Results: There were 26,595 patients (2024 CDA). ACDF patients were older, more likely to be female, discharged to inpatient rehabilitation, and have a history of obesity, smoking, diabetes, steroid use, and the American Society of Anesthesiologists-class ≥3. ACDF had greater median RVUs-per-case (41.2 vs. 24.1) and RVUs-per-minute (0.36 vs. 0.27), despite greater operative-time (109 min vs. 92 min) (P < 0.001). ACDF predicted a 16.9 unit increase in median RVUs per case (P < 0.001, confidence interval [CI]95: 16.3-17.5), an 8.81 min increase in median operative time per case (P < 0.001, CI95: 5.69-11.9), and 0.119 unit increase in median RVUs-per-minute (P < 0.001, CI95: 0.108-0.130). ACDF was associated with greater unadjusted rates of readmission (3.2% vs. 1.4%) morbidity (2.3% vs. 1.1%) (P < 0.001), but similar rates of reoperation (1.3% vs. 0.8%, P = 0.080). After adjusting for significant patient-related and procedural factors, readmission (odds ratio [OR] = 0.695, P = 0.130, CI95: 0.434-1.113) and morbidity (OR = 1.102, P = 0.688, CI95: 0.685-1.773) was similar between ACDF and CDA. Conclusions: Median RVUs-per-minute increased by 0.119 points for ACDF over CDA, or $257.7/h for each additional-hour of surgery. Adjusted 30-day outcomes were similar between procedures. Reimbursement for CDA does not appear to be in line with ACDF and may be a barrier to widespread usage.
RESUMO
BACKGROUND: At an interim analysis (median follow-up, 6.2 months; n = 187), the phase 3 COSMIC-311 trial met the primary end point of progression-free survival (PFS): cabozantinib improved PFS versus a placebo (median, not reached vs. 1.9 months; p < .0001) in patients with previously treated radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). The results from an exploratory analysis using an extended datacut are presented. METHODS: Patients 16 years old or older with RAIR-DTC who progressed on prior lenvatinib and/or sorafenib were randomized 2:1 to oral cabozantinib tablets (60 mg/day) or a placebo. Placebo patients could cross over to open-label cabozantinib upon radiographic disease progression. The objective response rate (ORR) in the first 100 randomized patients and the PFS in the intent-to-treat population, both according to Response Evaluation Criteria in Solid Tumors version 1.1 by blinded, independent review, were the primary end points. RESULTS: At the data cutoff (February 8, 2021), 258 patients had been randomized (cabozantinib, n = 170; placebo, n = 88); the median follow-up was 10.1 months. The median PFS was 11.0 months (96% confidence interval [CI], 7.4-13.8 months) for cabozantinib and 1.9 months (96% CI, 1.9-3.7 months) for the placebo (hazard ratio, 0.22; 96% CI, 0.15-0.32; p < .0001). The ORR was 11.0% (95% CI, 6.9%-16.9%) versus 0% (95% CI, 0.0%-4.1%) (p = .0003) with one complete response with cabozantinib. Forty placebo patients crossed over to open-label cabozantinib. Grade 3/4 treatment-emergent adverse events occurred in 62% and 28% of the cabozantinib- and placebo-treated patients, respectively; the most common were hypertension (12% vs. 2%), palmar-plantar erythrodysesthesia (10% vs. 0%), and fatigue (9% vs. 0%). There were no grade 5 treatment-related events. CONCLUSIONS: At extended follow-up, cabozantinib maintained superior efficacy over a placebo in patients with previously treated RAIR-DTC with no new safety signals.
Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Humanos , Adolescente , Radioisótopos do Iodo/uso terapêutico , Anilidas/efeitos adversos , Piridinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêuticoRESUMO
Oncogenic RET fusions occur in diverse cancers. Pralsetinib is a potent, selective inhibitor of RET receptor tyrosine kinase. ARROW ( NCT03037385 , ongoing) was designed to evaluate pralsetinib efficacy and safety in patients with advanced RET-altered solid tumors. Twenty-nine patients with 12 different RET fusion-positive solid tumor types, excluding non-small-cell lung cancer and thyroid cancer, who had previously received or were not candidates for standard therapies, were enrolled. The most common RET fusion partners in 23 efficacy-evaluable patients were CCDC6 (26%), KIF5B (26%) and NCOA4 (13%). Overall response rate, the primary endpoint, was 57% (95% confidence interval, 35-77) among these patients. Responses were observed regardless of tumor type or RET fusion partner. Median duration of response, progression-free survival and overall survival were 12 months, 7 months and 14 months, respectively. The most common grade ≥3 treatment-related adverse events were neutropenia (31%) and anemia (14%). These data validate RET as a tissue-agnostic target with sensitivity to RET inhibition, indicating pralsetinib's potential as a well-tolerated treatment option with rapid, robust and durable anti-tumor activity in patients with diverse RET fusion-positive solid tumors.
Assuntos
Neoplasias , Pirazóis , Piridinas , Pirimidinas , Fusão Gênica , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Proteínas Proto-Oncogênicas c-ret/genética , Pirazóis/efeitos adversos , Piridinas/efeitos adversos , Pirimidinas/efeitos adversosRESUMO
Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.
Assuntos
Adenocarcinoma , Antineoplásicos , Neoplasias da Glândula Tireoide , Antineoplásicos/uso terapêutico , Estudos de Coortes , Humanos , Radioisótopos do Iodo/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Quinolinas , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/radioterapiaRESUMO
PURPOSE: The androgen receptor (AR) is expressed (+) in a subset of salivary gland cancers (SGCs). This phase II trial evaluated the efficacy of the antiandrogen enzalutamide in AR+ SGC. METHODS: Patients with locally advanced/unresectable or metastatic AR+ SGCs were enrolled. Enzalutamide (160 mg) was given orally once daily. The primary end point was the best overall response rate per RECIST v1.1 within eight cycles. Confirmed responses in ≥ 5 of 41 patients would be considered promising. Secondary end points were progression-free survival, overall survival, and safety. RESULTS: Forty-six patients were enrolled; 30 (65.2%) received prior systemic therapy, including 13 (28.3%) with AR-targeted drugs. Of seven (15.2%) partial responses (PRs), only two (4.3%) were confirmed per protocol and counted toward the primary end point. Twenty-four patients (52.2%) had stable disease; 15 (32.6%) had progression of disease as best response. Twenty-six patients (56.5%) experienced tumor regression in target lesions; 18 (39.1%) had partial response/stable disease ≥ 6 months. Tumor regressions were observed in female patients (5 of 6 [83.3%]) and those who received prior AR- (6 of 13 [46.2%]) or human epidermal growth factor receptor 2-targeted therapies (5 of 8 [62.5%]). Three patients remained on treatment at data cutoff (duration, 32.2-49.8 months). The median progression-free survival was 5.6 months (95% CI, 3.7 to 7.5); the median overall survival was 17.0 months (95% CI, 11.8 to 30.0). The most common adverse events were fatigue, hypertension, hot flashes, and weight loss. Total and free testosterone levels increased by a mean of 61.2% and 48.8%, respectively, after enzalutamide. CONCLUSION: Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.
Assuntos
Nitrilas , Feniltioidantoína , Neoplasias das Glândulas Salivares , Feminino , Humanos , Masculino , Antagonistas de Androgênios/efeitos adversos , Nitrilas/efeitos adversos , Feniltioidantoína/efeitos adversos , Receptores Androgênicos/metabolismo , Neoplasias das Glândulas Salivares/tratamento farmacológico , Neoplasias das Glândulas Salivares/patologiaRESUMO
OBJECTIVE: To determine whether operative duration of anterior cervical discectomy and fusion (ACDF) significantly affects patient-reported outcome measures (PROMs) 90 days after surgery and at 1-year follow-up. METHODS: Patients who underwent primary 1-level to 4-level ACDF were retrospectively identified. Demographic data and PROMs were collected through chart review. Patients were split into short, medium, and long tertiles based on procedure duration. PROM surveys were administered preoperatively as baseline measurements, at initial follow-up (between 60 and 120 days postoperatively), and at 1 year postoperatively. Outcomes included Neck Disability Index, Short-Form 12 Physical Component Score (PCS-12), Short-Form 12 Mental Component Score, visual analog scale (VAS) neck score, and VAS arm score. RESULTS: Significant short-term improvements were found across all groups for all PROMs. All groups showed long-term improvements in Short-Form 12 Mental Component Score, PCS-12, Neck Disability Index, VAS neck score, and VAS arm score, with the exception of the medium-duration group in PCS-12 (P = 0.093). On multivariate analysis, short-duration procedures predicted better improvement in VAS neck score (ß = -1.01; P = 0.012) and VAS arm score (ß = -1.38; P = 0.002) compared with long-duration procedures, whereas medium-duration procedures resulted in better improvement in VAS arm score (ß = -1.00; P = 0.011). Further, short and medium duration was a predictor of decreased length of hospital stay (ß = -0.67, P = 0.001 and ß = -0.59, P = 0.001, respectively) compared with long-duration procedures. CONCLUSIONS: All groups improved after ACDF regardless of surgical duration. Further, surgical duration was not a predictor of differing improvement in physical function or disability.
Assuntos
Vértebras Cervicais , Fusão Vertebral , Vértebras Cervicais/cirurgia , Discotomia/métodos , Humanos , Medidas de Resultados Relatados pelo Paciente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Tofacitinib is the only medicine in the class of Janus kinase (JAK) inhibitors that has been approved for use in moderate-to-severely active ulcerative colitis (UC). The potential of other JAK inhibitors to treat UC has not been fully explored. We present a case describing the successful use of the selective JAK inhibitor, ruxolitinib, to treat a patient with concomitant UC and polycythemia vera.