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1.
Oncologist ; 27(6): 487-492, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35278074

RESUMO

BACKGROUND: Many randomized control trials (RCTs) evaluating programmed death receptor-1 (PD-1)/programmed death ligand-1 (PD-L1) targeting monoclonal antibodies (mAbs) have been completed or are in progress. We examined hypothesized hazard ratios (HHRs) and observed hazard ratios (OHRs) from published RCTs evaluating these mAbs. METHODS: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary reports of RCTs were retrieved. Two investigators extracted HHR, OHR for the primary endpoint among other data elements independently. The differences (∆HR) in HHR and OHR were analyzed statistically. A separate search was conducted for secondary reports after longer follow-ups, the updated OHR was extracted. RESULTS: Forty-nine RCTs enrolling 36 867 patients were included. The mean HHR and OHR were 0.672 and 0.738 respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895; 95% confidence interval (CI), 0.003-0.130). HHR was met or exceeded in 22 (45%) RCTs. OHR was ≥ 1.0 in 6 RCTs (12%). PD-L1 expression was not associated with the magnitude of effect. Of 18 RCTs with follow-up reports, the magnitude of benefit decreased in 8 RCTs with extended follow-ups. CONCLUSION: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of benefit. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in a variety of disease settings.


Assuntos
Antineoplásicos Imunológicos , Neoplasias , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1 , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias/tratamento farmacológico , Receptor de Morte Celular Programada 1 , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
BMC Cancer ; 22(1): 18, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34980015

RESUMO

PURPOSE: BRCA gene mutations (BRCAm) have an impact on patients' characteristics and clinical outcomes of ovarian cancer (OC). The frequency and patterns of BRCAm vary among countries and ethnicities. There are limited data from Saudi Arabia (SA); thus, this study aims to determine the frequency, pattern, and impact on patient characteristics and outcomes of BRCAm OC compared to wild-type BRCA (BRCAw) in Saudi women. METHODS: This retrospective study evaluated women diagnosed with non-mucinous OC, fallopian tube, or peritoneal carcinoma who had BRCA status tested in an accredited lab between January 2016 and December 2017. The associations between various parameters and BRCAm were estimated using logistic regression. Statistical analysis performed with SPSS (Version 27). RESULT: Sixty-one women with a median age of 52 at diagnosis were analyzed. Germline BRCA mutations were found in 41% of cases (25/61). The most common deleterious germline BRCA1 mutation was c.1140dupG (39%). Most women (72%) had no family history of cancers and 82% had advanced stage. Regardless of BRCA mutations, an optimal overall response rate (ORR) to first-line treatment has been achieved although most cases relapsed (84%) and the majority were platinum-sensitive relapse (85%). Higher ORR to subsequent lines and better survival were obtained in women with BRCA-mutation. CONCLUSION: The prevalence of BRCAm of OC was higher in Saudi women compared to regional and most of the international figures. The better clinical outcomes of BRCAm women agreed with the reported evidence. Further studies on BRCA mutations of OC and genetic counseling are highly recommended. TRIAL REGISTRATION: Trial approved by the Institutional Review Board of King Faisal Specialist Hospital and Research Center (RAC # 2171137) and conducted at King Faisal Specialist Hospital and Research Center, PO Box 3354, Riyadh 11,211, Saudi Arabia.


Assuntos
Proteína BRCA1/análise , Proteína BRCA2/análise , Neoplasias das Tubas Uterinas/genética , Neoplasias Ovarianas/genética , Neoplasias Peritoneais/genética , Adulto , Etnicidade/genética , Neoplasias das Tubas Uterinas/etnologia , Feminino , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/etnologia , Neoplasias Peritoneais/etnologia , Estudos Retrospectivos , Arábia Saudita/etnologia
3.
J Geriatr Oncol ; 13(3): 318-324, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34924306

RESUMO

BACKGROUND: Grip strength (GS) and the Short Physical Performance Battery (SPPB) are brief objective tests used during a comprehensive geriatric assessment (CGA) to assess physical performance. Abnormal GS and SPPB scores are associated with greater morbidity and mortality in older adults with cancer but their relationship with chemotherapy tolerability is unclear. We explored the performance of GS and SPPB in predicting therapy delay, dose reduction, and treatment completion in older adults undergoing chemotherapy or chemoradiation. Additionally, we examined associations between GS, SPPB, and instrumental activities of daily living (IADLs). METHODS: Retrospective review of patients ≥65 years old who had undergone a pre-treatment CGA in a geriatric oncology clinic were retrieved from electronic charts and institutional databases. Abnormal GS was defined as <26 kg and < 16 kg for men and women, respectively. Abnormal SPPB was defined as ≤9 points. Logistic regression was used to examine the associations between abnormal GS or SPPB alone or combined with chemotherapy-related outcomes (e.g., delay, dose reduction, completion). Chi-squared tests were used to determine associations between physical performance measures (GS and SPPB) and IADLs. RESULTS: A total of 85 participants (mean age 79.1 years old) with mixed cancer diagnoses were included. Approximately 67% of participants exhibited abnormal GS or SPPB prior to treatment. Abnormal GS or SPPB (combined) was associated with treatment delay (odds ratio (OR) = 7.58, 95% confidence interval (CI) = 1.77, 32.43, P = 0.006). When physical performance measures were examined separately, only SPPB predicted treatment delay (OR = 3.26, 95%CI = 1.04, 10.21, P = 0.043). Abnormal GS or SPPB were not associated with dose reduction or treatment completion. Abnormal GS and SPPB alone or combined demonstrated only modest sensitivity (41.9-76.7%) and negative predictive value (57.9-64.2%) in identifying IADLs dependence. CONCLUSION: GS and SPPB may be used to predict treatment delay in older adults prior to chemotherapy and chemoradiation. Additional studies are warranted to examine whether GS and/or SPPB can predict dose reduction and treatment completion in older adults prior to receiving chemotherapy or chemoradiation.


Assuntos
Atividades Cotidianas , Neoplasias , Idoso , Feminino , Avaliação Geriátrica , Força da Mão , Humanos , Masculino , Neoplasias/tratamento farmacológico , Desempenho Físico Funcional
4.
J Cancer ; 12(14): 4372-4378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093837

RESUMO

Background: Multiple anti-PD-1/PD-L1 antibodies have been approved, and in some diseases, there is a choice of more than one. Comparative efficacy, safety and tolerability are unknown. Methods: Randomized trials (RCTs) supporting the registration of single agent anti-PD1 or anti-PDL1 inhibitors between 2015-2019 were identified. We extracted the hazard ratio (HR) for overall survival (OS) and calculated the odds ratio (OR) for commonly reported safety and tolerability outcomes. We then performed a network meta-analysis, reporting multiple pair-wise comparisons between different anti-PD-1/PD-L1 antibodies. Results: Sixteen RCTs comprising 10673 patients were included; 10 in non-small-cell lung cancer, 2 in melanoma, 2 in head and neck squamous cell carcinoma and 2 in urothelial cancer. Compared to pembrolizumab, efficacy was similar for nivolumab (HR: 1.02 95% CI: 0.91-1.14) and for atezolizumab (HR: 0.97 95% CI: 0.85-1.10), however, avelumab appeared inferior (HR: 1.30, 95% CI: 1.06-1.56). Pembrolizumab showed similar odds of serious adverse events (SAEs) as nivolumab (OR: 1.12, 95% CI: 0.56-2.27) and atezolizumab (OR: 1.05, 95% CI: 0.55-2.04). Compared to nivolumab, atezolizumab was associated with more SAEs (OR: 2.14, 95% CI: 1.47-3.12). Avelumab had the lowest odds of grade 3-4 adverse events compared to pembrolizumab (OR: 0.42, 95% CI: 0.24-0.74), nivolumab (OR: 0.38, 95% CI: 0.24-0.62) and atezolizumab (OR: 0.21, 95% CI: 0.14-0.33). The odds of treatment discontinuation without progression were similar between nivolumab and atezolizumab (OR: 1.20, 95% CI: 0.73-2.00), and between pembrolizumab and nivolumab (OR: 1.35, 95% CI: 0.83-2.17), but was higher with atezolizumab compared to nivolumab (OR: 2.56, 95% CI: 1.29-5.00). Pembrolizumab was associated with higher OR of immune-related adverse events (IRAEs) compared to nivolumab (OR: 2.12, 95% CI: 1.49-3.03) and atezolizumab (OR: 1.63, 95% CI: 1.09-2.43). Conclusions: Pembrolizumab, nivolumab, and atezolizumab have similar efficacy. Avelumab appears less efficacious. Safety and tolerability seem better with avelumab, but worse with atezolizumab and pembrolizumab.

5.
Nucl Med Commun ; 42(8): 899-906, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33852535

RESUMO

BACKGROUND: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding 18F-labelled fluoro-2-deoxyglucose (FDG)-PET use in NLPHL. We are reporting our experience with FDG-PET utility in staging and response assessment NLPHL patients. METHODS: We retrospectively studied a population of all newly diagnosed or relapsed/refractory patients who underwent both pre-treatment contrast-enhanced computed tomography (CeCT) and an FDG-PET and also at the end of planned treatment. RESULTS: We identified 68 patients found to have in total 312 scans, 78 paired pre-therapeutic and post-treatment CeCT and FDG-PET scans. Among them, 55 were male, with a median follow-up was 48 months. Median SUV-max was 8.3 (2.0-21.0). FDG-PET and CeCT were concordant in 80% (62/78) of staging scans. In 20% (16/78) of patients in whom a discordance was observed, FDG-PET resulted in upstaging in 13 scans and downstaging in 3 scans. The sensitivity of CeCT was 92% for nodal staging and 42% for extralymphatic staging when compared to FDG-PET. The specificity of CeCT was 98% as compared to FDG-PET. For response assessment, there was poor agreement between the CeCT and FDG-PET in assigning complete remission of disease scores as FDG-PET was able to identify the absence of disease despite the presence of a radiologically evident residual mass on CeCT. The sensitivity for CeCT compared to FDG-PET was 100% while the specificity was 43% for detection of post-treatment response. CONCLUSION: For NLPHL, pre-therapeutic FDG-PET scan is better than CeCT staging. FDG-PET has much better specificity for response assessment than CeCT.


Assuntos
Fluordesoxiglucose F18 , Doença de Hodgkin , Tomografia por Emissão de Pósitrons , Adulto , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
J Geriatr Oncol ; 12(5): 786-792, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33342723

RESUMO

BACKGROUND: The Vulnerable Elders Survey (VES-13) is commonly used to identify older patients who may benefit from Comprehensive Geriatric Assessment (CGA) prior to cancer treatment. The optimal cut point of the VES-13 to identify those whose final oncologic treatment plan would change after CGA is unclear. We hypothesized that patients with high positive VES-13 scores (7-10)have a higher likelihood of a change in treatment compared to low positive scores (3-6). METHODS: Retrospective review of a customized database of all patients seen for pre-treatment assessment in an academic geriatric oncology clinic from June 2015 to June 2019. Various VES-13 cut points were analyzed to identify those individuals whose treatment was modified after CGA. Area under the curve (AUC) was calculated and subgroups of patients treated locally or systemically were also examined to determine if performance varied by treatment modality. RESULTS: We included 386 patients with mean age 81, 58% males. Gastrointestinal cancer was the most common site (31%) and 60% were planned to receive curative treatment. The final treatment plan was modified in 59% overall, with 52.7% modified with VES-13 scores 7-10, 50.8% with scores 3-6 and 28.1% with scores <3 (P = 0.002). VES-13 performance in predicting treatment modification was similar for cut points 3 (AUC 0.58), 4 (0.59), 5 (0.59), and 6 (0.59) and in those considering local treatment vs. chemotherapy. CONCLUSIONS: A positive VES-13 score was associated with final oncologic treatment plan modification. A high positive score was not superior to the conventional cut point of ≥3.


Assuntos
Detecção Precoce de Câncer , Neoplasias Gastrointestinais , Idoso , Idoso de 80 Anos ou mais , Feminino , Avaliação Geriátrica , Humanos , Masculino , Estudos Retrospectivos , Inquéritos e Questionários
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