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Introduction: KEYNOTE-394 showed pembrolizumab significantly improved overall survival, progression-free survival, and objective response rate with manageable safety versus placebo for patients from Asia with previously treated advanced hepatocellular carcinoma. We present results on health-related quality of life (HRQoL). Methods: HRQoL was evaluated using the EORTC Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and EuroQol-5D-3L (EQ-5D-3L) questionnaires. Key HRQoL endpoints were least squares mean (LSM) score changes from baseline to week 12 and time to deterioration (TTD) for EORTC QLQ-C30 global health status (GHS)/QoL. p values were one-sided and nominal without adjustment for multiplicity. Results: The HRQoL population included patients randomly assigned to pembrolizumab (n = 298) and placebo (n = 152). From baseline to week 12, a greater decline in EORTC QLQ-C30 GHS/QoL score was observed with placebo (LSM, -8.4; 95% CI: -11.7 to -5.1) versus pembrolizumab (-4.0; 95% CI: -6.4 to -1.6; difference vs. placebo: 4.4; 95% CI: 0.5-8.4; nominal p = 0.0142). Similarly, a greater decline in the EQ-5D-3L visual analog scale score was observed with placebo (-6.9; 95% CI: -9.4 to -4.5) versus pembrolizumab (-2.7; 95% CI: -4.5 to -1.0; difference vs. placebo: 4.2; 95% CI: 1.2-7.2; nominal p = 0.0030). TTD in EORTC QLQ-C30 GHS/QoL score was similar between arms (hazard ratio, 0.85; 95% CI: 0.58-1.25; nominal p = 0.1993). Conclusion: Patients receiving placebo showed a greater decline in HRQoL than those receiving pembrolizumab. Combined with efficacy and safety data from KEYNOTE-394 and the global KEYNOTE-240 and KEYNOTE-224 trials, our data support the clinically meaningful benefit and manageable tolerability of pembrolizumab as second-line therapy for patients with advanced hepatocellular carcinoma.
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Recent data from several randomized controlled trials (RCTs) have shown that Total Neoadjuvant Therapy (TNT) can improve the treatment outcome of patients with high-risk rectal cancer from Western and East Asian populations. Systemic intensification with chemotherapy administered before (induction) or after (consolidation) neoadjuvant radiotherapy (RT) prior to total mesorectal excision (TME) surgery has been shown to improve disease-free survival (DFS), pathologic complete response (pCR) rate, treatment compliance and/or reduce the risk of disease-related treatment failure for high-risk rectal cancer. In this review we highlighted the key results of RCTs on different TNT approaches conducted in Western and Asian populations, and their impact on clinical practice and research direction. We discussed the salient issues and controversies arising from these studies such as the optimal duration of TNT, factors affecting patient selection and the feasibility of adopting a watch-and-wait approach in complete responders to TNT. There are considerable variations between treatment guidelines from Western and East Asian regions on adopting TNT in the management of high-risk rectal cancer, therefore reflecting regional differences in oncologist's preferences and feasibility in implementing TNT. The review concluded by providing an update on some of the key ongoing RCTs into a risk-adapted approach to incorporating TNT in clinical practice, and also translational research into predictive and prognostic biomarkers of response to TNT for high risk rectal cancer.
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Terapia Neoadyuvante , Neoplasias del Recto , Quimioradioterapia/métodos , Humanos , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Neoplasias del Recto/patología , Recto/patología , Resultado del TratamientoRESUMEN
PURPOSE OF THE STUDY: To evaluate the benefits and tolerability of regorafenib in the real-world setting, we performed a multicentre analysis in Hong Kong. STUDY DESIGN: Individual patient data were retrieved from three leading oncology centres in Hong Kong for analyses. All patients with metastatic colorectal cancer (mCRC) treated with regorafenib after failure of all standard systemic options were included. RESULTS: From July 2013 to December 2015, 45 consecutive patients treated with regorafenib for mCRC were analysed. The median age was 63. Twenty patients were started at 160â mg, while the other 25 patients were started at a lower dose. The median progression-free survival was 15.6â weeks (95% CI 13.1 to 18.1â weeks) and the median overall survival was 30.4â weeks (95% CI 16.6 to 44.3â weeks). Among the 31 evaluable patients, only 1 patient (3.2%) achieved partial response and another 10 patients (32.3%) had stable disease. The commonest grade 3 non-haematological adverse event (AE) was hand-foot skin reaction (26.7%) and the commonest grade 3 or 4 haematological AE was anaemia (8.9%). Notably, patients who were started on a lower dose of regorafenib had significantly lower risk of grade 3 treatment-emergent AEs. Overall, 78.3% of the patients had dose reduction during the first and second cycles. Patients older than 65â years were more likely to experience cycle suspension and require dose reduction. CONCLUSIONS: Our study confirmed the efficacy and tolerability of regorafenib in the real-world setting. It also suggested that individualised dosing of regorafenib in patients with mCRC might result in better clinical outcomes.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Compuestos de Fenilurea/uso terapéutico , Piridinas/uso terapéutico , Anciano , Femenino , Hong Kong , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de SupervivenciaRESUMEN
PURPOSE: To study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The treatment outcomes of NPC patients treated with IMRT at Pamela Youde Nethersole Eastern Hospital between 2005 and 2007 were reviewed. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. Statistical analyses were performed on dose coverage and locoregional failures. RESULTS: A total of 193 NPC patients were analyzed; 93% had Stage III/IV disease. Median follow-up was 30 months. Overall disease failure (at any site) developed in 35 patients. Among these, there were 23 distant metastases, 16 local failures, and 9 regional failures. Four of the locoregional failures were marginal. Dose conformity with IMRT was excellent. Patients with at least 66.5 Gy to their target volumes had significantly less locoregional failure. The 2-year local progression-free, regional progression-free, distant metastasis-free, and overall survival rates were 95%, 96%, 90%, and 92%, respectively. CONCLUSIONS: Intensity-modulated radiotherapy provides excellent locoregional control for NPC. Distant metastasis remains the most difficult challenge, and more effective systemic agents should be explored for patients presenting with advanced locoregional diseases.