scholarly journals Comparison of TPF and TP Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma Based on TNM Stage and Pretreatment Systemic Immune-Inflammation Index

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Xiong ◽  
Liangliang Shi ◽  
Lisheng Zhu ◽  
Gang Peng
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Stage Iii ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Optimal Value ◽  
Grade 3 ◽  
Cox Proportional Hazard Regression

PurposeTo evaluate the efficacy and toxicity of the two IC (induction chemotherapy) regimens, TPF (taxanes, cisplatin, and 5-fluorouracil) and TP (taxanes and cisplatin) combined with concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients.MethodsUltimately, we enrolled 213 patients at stage III-IVA in this retrospective study. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The toxicities were evaluated according to CTCAE v4.0 and RTOG criteria.ResultsTPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients. The optimal value of pretreatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with SII ≥432.48 showed superior OS (P=0.038) and DMFS (P=0.028) from TPF. Also, SII was proved to be a prognostic element for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032) in multivariate analysis, and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3–4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048), diarrhea (P=0.036), and ear damage (P=0.046) were more common in TPF group.ConclusionOur study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while for stage III and N0-1, TP might be ample. In high-risk LA-NPC patients (stage IVA combined with pretreatment SII ≥432.48), TPF had a higher 5-year OS and DMFS, with more grade 3–4 toxicities, but most of them were endurable.

scholarly journals Comparison of TPF and TP Induction Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma Based on TNM Stage and Pretreatment Systemic Immune-Inflammation Index

2021 ◽  
Author(s):  
Ying Xiong ◽  
Liang liang Shi ◽  
Sheng li Zhu ◽  
Gang Peng
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Locally Advanced ◽  
Stage Iii ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Optimal Value ◽  
Pre Treatment ◽  
Grade 3 ◽  
Cox Proportional Hazard Regression

Abstract Background: Induction chemotherapy (IC) was associated with a decreased risk of distant metastasis in locally advanced nasopharyngeal carcinoma (LA-NPC). However, compared with TPF, whether the TP regimen can reduce the related toxicities caused by 5-FU while ensuring the survival benefit remains unclear.Methods: 213 patients diagnosed with LA-NPC (stage III-IVA) were included retrospectively. The prognosis of TPF and TP was compared by Kaplan-Meier and Cox proportional hazard regression. The treatment-related toxicities were evaluated according to CTCAE v4.0 and RTOG criteria. Results: TPF was found to have a higher 5-year DMFS in stage IVA and N2-3 patients, which not applicable to stage III and N0-1. The optimal value of pre-treatment SII was 432.48. A further subgroup analysis revealed that patients in stage IVA combined with pretreatment SII≥432.48 could get higher OS (P=0.038) and DMFS (P=0.028) from TPF. Multivariate analysis showed that SII was a prognostic factor for PFS (HR 2.801, P=0.018) and DMFS (HR 3.735, P=0.032), and IC regimen (HR 2.182, P=0.049) for predicting DMFS. The rate of grade 3-4 leukopenia (P=0.038), neutropenia (P=0.021), radiation oral mucositis (P=0.048) and diarrhea (P=0.036) were more common in TPF group. Conclusion: Our study revealed that TPF regimen showed a higher 5-year DMFS for stage IVA and N2-3 patients, while TP may be enough for stage III and N0-1. In LA-NPC patients with high risk (stage IVA combined with pre-treatment SII ≥ 432.48), TPF had a higher 5-year OS and DMFS, although grade 3-4 toxicities were more common but tolerable.

Cisplatin and capecitabine induction chemotherapy in nasopharyngeal carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6065-6065
Author(s):  
Zhiyuan Xu ◽  
Li Yang ◽  
Victor Ho-Fun Lee ◽  
Anne W. M. Lee
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Residual Disease ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Neck Region ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Grade 3

6065 Background: Induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) is now one of the standard treatment for locally advanced nasopharyngeal carcinoma (LANPC). Cisplatin/fluorouracil is one of the recommended IC regimens. Capecitabine is an oral fluoropyrimidine prodrug with higher concentrations of fluorouracil attained in the tumor cells after enzymatic conversions. We conducted this study to evaluate the feasibility, efficacy and safety of cisplatin and capecitabine (PX) IC followed by CCRT in LANPC. Methods: Newly diagnosed patients with LANPC (stage III-IVB according to 7th edition of AJCC/UICC system [TNM-7] and stage III-IVA according to 8th edition [TNM-8) were prospectively recruited from January 2015 to October 2019. They received induction PX (cisplatin: 80mg/m2 on day 1 + capecitabine: 1000mg/m2 twice daily from day 1 to 14 every 3 weeks for 3 cycles) followed by CCRT (cisplatin: 100mg/m2 every 3 weeks for a total of 2-3 cycles concurrent with intensity-modulated radiation therapy [IMRT]). IMRT with doses of 70Gy, 63Gy and 56Gy were delivered to 3 levels of planning target volumes (PTV) (high, intermediate and low risk) respectively and simultaneously in 35 fractions/7 weeks. Tumor response by MRI and CT was evaluated after completion of IC and 16 weeks after completion of CCRT according to RECIST v1.1. All adverse events were graded with NCI CTCAE v4.03. Results: One hundred and forty-five patients were recruited. The stage distributions according to TNM-8 were 82(56.6%) and 63(43.3%) for stage III and IVA, respectively. One hundred and thirty-seven patients completed 3 cycles of induction PX and 122 patients completed IMRT with 2 to 3 cycles of concurrent cisplatin. The median (interquartile range, IQR) tumor regression rates after 2-3 cycles of PX at the nasopharynx (NP) and the neck region (NK) were 51.2% (37.3%-66.5%) and 71.8% (56.7%-81.1%), respectively. At 16 weeks after CCRT, only one patient had residual disease. After a median follow-up of 33 months, 20 treatment failures and 8 deaths were observed. The estimated 2-year progression-free survival (PFS) and overall survival (OS) were 89.8% and 97.2%. The rates of grade 3/4 leukopenia, neutropenia, anemia, nausea/vomiting and electrolyte disturbance during IC were 6.2%, 15.9%, 6.9%, 4.1% and 9.0%, respectively. The corresponding rates were 45.1%, 24.6%, 27.5%, 2.8% and 11.3% during CCRT. Only 1 (0.7%) grade 3/4 hand-foot syndrome and 3 (2.1%) grade 3/4 diarrhea during IC were observed. The rates of grade 3/4 mucositis and dermatitis were 31.0% and 12.7%, respectively. There were no treatment-related deaths. Conclusions: Induction PX followed by CCRT was effective and well tolerated in patients with LANPC. Clinical trial information: NCT03427359.

scholarly journals Survival of the Recidivistic? Revealing Factors Associated with the Criminal Career Length of Multiple Homicide Offenders

2020 ◽  
Author(s):  
Gian Maria Campedelli ◽  
Enzo Yaksic
Keyword(s):  
Criminal Career ◽  
Proportional Hazard ◽  
Multiple Methods ◽  
Factors Associated ◽  
Career Length ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Inferential Analysis ◽  
Cox Proportional Hazard Regression ◽  
Multiple Homicide

Relying on a sample of 1,394 US-based multiple homicide offenders (MHOs), we study the duration of the careers of this extremely violent category of offenders through Kaplan-Meier estimation and Cox Proportional Hazard regression. We investigate the characteristics of such careers in terms of length and we provide an inferential analysis investigating correlates of career duration. The models indicate that females, MHOs employing multiple methods, younger MHOs and MHOs that acted in more than one US state have higher odds of longer careers. Conversely, those offending with a partner and those targeting victims from a single sexual group have a higher probability of shorter careers.

scholarly journals Factors predicting the success of trabeculectomy bleb enhancement with needling

2018 ◽  
Vol 102 (12) ◽  
pp. 1667-1671 ◽  
Author(s):  
Jonathan Y-X L Than ◽  
Toby S Al-Mugheiry ◽  
Jesse Gale ◽  
Keith R Martin
Keyword(s):  
Proportional Hazard ◽  
Glaucoma Medication ◽  
Safety And Efficacy ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Retrospective Audit ◽  
Lower Likelihood ◽  
Period Data ◽  
Cox Proportional Hazard Regression ◽  
Medication Risk

BackgroundBleb needling is widely used to restore flow and lower intraocular pressure (IOP) in a failing trabeculectomy. We aimed to measure the safety and efficacy of needling in a large cohort and identify factors that were associated with success and failure.MethodsThis retrospective audit included all patients who underwent needling at Addenbrooke’s Hospital, Cambridge over a 10-year period. Data were available on 91 patients (98% of patients identified), including 191 needlings on 96 eyes. Success was defined as IOP below 21 mm Hg or 16 mm Hg or 13 mm Hg consistently, without reoperation or glaucoma medication. Risk factors for failure were assessed by Cox proportional hazard regression and Kaplan-Meier curves.ResultsSuccess defined as IOP <16 mm Hg was 66.6% at 12 months and 53% at 3 years and success defined as IOP <21 mm Hg was 77.1% at 12 months and 73.1% at 3 years. Failure after needling was most common in the first 6 months. Factors that predicted failure were flat or fibrotic blebs (non-functional) and no longer injected, while success was predicted by achieving a low IOP immediately after needling. No significant complications were identified.ConclusionNeedling was most successful soon after trabeculectomy, but resuscitation of a long-failed trabeculectomy had lower likelihood of success. The safety and efficacy compare favourably with alternative treatment approaches.

scholarly journals CMTM6 significantly relates to PD-L1 and predicts the prognosis of gastric cancer patients

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9536
Author(s):  
Xin Li ◽  
Ling Chen ◽  
Chuan Gu ◽  
Qiaoli Sun ◽  
Jia Li
Keyword(s):  
Gastric Cancer ◽  
Prognostic Indicator ◽  
Proportional Hazard ◽  
Regression Analyses ◽  
Multivariate Logistic Regression ◽  
Related Factors ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Regression ◽  
The Relationship

Background The CKLF-like MARVEL transmembrane domain containing 6 (CMTM6) is a key regulator of the programed death receptor ligand-1 (PD-L1) protein. However, the usefulness of CMTM6 expression as a prognostic indicator and the relationship between CMTM6 and PD-L1 expression in gastric cancer (GC) remains unclear. Objectives We evaluated the expression and prognostic implications of CMTM6 in GC tissue and its relationship with PD-L1 expression. Patients and methods The protein expressions of CMTM6 and PD-L1 were detected in 122 cases of postoperative GC tissue using immunohistochemical (IHC) assays. Kaplan–Meier survival analysis was used to calculate the survival probability and a log-rank test was used to compare the survival curves. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the clinically-related factors associated with survival. Pearson’s correlation was used to determine the correlation analysis and estimate the statistical significance. The univariate and multivariate logistic regression analyses were used to analyze the relationship between clinically-related factors and PD-L1 expression. Results Kaplan–Meier survival analysis showed that patients with high CMTM6 expression had shorter overall survival (OS) than those with low expression (P < 0.001). The expression of CMTM6 was an independent risk factor for prognosis in multivariate Cox proportional hazard regression analyses (HR:2.221, CI% [1.36–3.628], P = 0.001). The OS of patients with positively expressed PD-L1 was significantly shorter than those with negatively expressed PD-L1 (P = 0.003). The expression of CMTM6 was significantly related to the positive expression of PD-L1 in gastric cancer tissues (r = 0.186, P = 0.041). The expression of CMTM6 was the independent risk factor for PD-L1 expression in multivariate logistic regression analysis (OR:2.538, CI% [1.128–5.714], P = 0.024). Conclusion CMTM6 expression is significantly related to PD-L1 and may be a useful prognostic indicator and a specific therapeutic target for cancer immunotherapy for GC patients.

scholarly journals Comparison of non-schistosomal colorectal cancer and schistosomal colorectal cancer

2020 ◽  
Author(s):  
Weixia Wang ◽  
Kui Lu ◽  
Limei Wang ◽  
Hongyan Jing ◽  
Weiyu Pan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Clinical Stage ◽  
Clinicopathological Features ◽  
Proportional Hazard ◽  
Node Metastasis ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Regression

Abstract Aim: The purpose of this study was to compare clinicopathological features of patients with non-schistosomal and schistosomal colorectal cancer to explore the effect of schistosomasis on CRC patients` clinical outcomes. Methods: 351 cases of CRC were retrospectively analyzed in this study. Survival curves were constructed by using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were performed to identify associations with outcome variables.Results: Patients with schistosomiasis (CRC-S) were significantly older (Table 3, P＜0.001) than patients without schistosomiasis (CRC-NS). However, there were no significant differences between CRC-S and CRC-NS patients in other clinicopathological features. Schistosomiasis were associated with adverse overall survival upon K-M analysis (P=0.0277). By univariate and multivariate analysis, as shown in Table 2, gender (P=0.003), TNM stage (P＜0.001), schistosomiasis (P=0.025), lymphovascular invasion (P=0.030) and cancer node (P＜0.001) were all independent predictors in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state. Schistosomiasis was also an independent predictors in patients with stage Ⅲ-Ⅳ tumors and in patients with lymph node metastasis, but not in patients with stage Ⅰ-Ⅱ tumors and in patients without lymph node metastasis.Conclusion: Schistosomiasis was significantly correlated with OS and it was an independent prognostic factor for OS in the whole cohort. When patients were stratified according to clinical stage and lymph node metastasis state, schistosomiasis was still an independent unfavorably prognosis factor for OS in patients with stage Ⅲ-Ⅳ tumors or patients with lymph node metastasis.

scholarly journals Pengaruh Status Nutrisi terhadap Kesintasan 30 Hari Pasien Geriatri yang Dirawat di Rumah Sakit

2017 ◽  
Vol 2 (3) ◽  
pp. 160
Author(s):  
Nata Pratama Hardjo Lugito ◽  
Czeresna Heriawan Soejono ◽  
Edy Rizal Wahyudi ◽  
Esthika Dewiasty
Keyword(s):  
Regression Model ◽  
Nutritional Assessment ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Mini Nutritional Assessment ◽  
Proportional Hazard ◽  
Geriatric Depression ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Cox Proportional Hazard Regression

Pendahuluan. Dengan meningkatnya jumlah populasi usia lanjut, masalah kesehatan yang dialami juga semakin banyak, salah satunya malnutrisi. Studi di luar negeri menunjukkan malnutrisi pada pasien geriatri yang dirawat di rumah sakit menurunkan kesintasan. Pasien usia lanjut di Indonesia mempunyai karakteristik yang berbeda dengan pasien usia lanjut di luar negeri. Di Indonesia belum ada studi tentang status nutrisi pasien usia lanjut yang dirawat di rumah sakit dan pengaruhnya terhadap kesintasan. Penelitian ini bertujuan mengetahui pengaruh status nutrisi terhadap kesintasan 30 hari pasien usia lanjut yang dirawat di ruang rawat akut geriatri dan ruang rawat penyakit dalam rumah sakit.Metode. Penelitian kohort retrospektif, dengan pendekatan analisis kesintasan, dilakukan terhadap 177 pasien geriatri yang dirawat di ruang rawat akut geriatri dan ruang rawat penyakit dalam Rumah Sakit Cipto Mangunkusumo selama bulan April–September 2011. Data demografis, diagnosis medis, kadar albumin, indeks ADL Barthel, geriatric depression scale, status nutrisi dengan mini nutritional assessment (MNA) dikumpulkan, dan diamati selama 30 hari sejak mulai dirawat untuk melihat ada tidaknya mortalitas. Perbedaan kesintasan kelompok pasien dengan status nutrisi baik, berisiko malnutrisi dan malnutrisi ditampilkan dalam kurva Kaplan-Meier, diuji dengan uji Log-rank, serta analisis multivariat dengan Cox proportional hazard regression model untuk menghitung adjusted Hazard Ratio dan interval kepercayaan 95% terjadinya mortalitas 30 hari dengan memasukkan variabel-variabel perancu sebagai kovariat.Hasil. Kesintasan antara subyek yang status nutrisinya baik, berisiko malnutrisi dan malnutrisi ialah 94,7% dengan 89,0% dan 80,7%, namun perbedaan kesintasan 30 hari tak bermakna dengan uji Log-rank (p=0,106). Pada analisis multivariat didapatkan adjusted HR setelah penambahan variabel perancu sebesar 1,49 (IK 95% 0,29 – 7,77) untuk kelompok berisiko malnutrisi dan 2,65 (IK 95% 0,47 – 14,99) untuk kelompok malnutrisi dibandingkan dengan pasien nutrisi baikSimpulan. Perbedaan kesintasan 30 hari pasien geriatri yang dirawat di rumah sakit yang menderita malnutrisi dan berisiko malnutrisi dibandingkan dengan status nutrisi baik pada awal perawatan belum dapat dibuktikan.

Safety study of induction chemotherapy and synchronous radiotherapy (RT) and cetuximab in stage III non-small cell lung cancer (NSCLC): SCRATCH (Cohort I)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18032-18032 ◽  
Author(s):  
S. R. Hughes ◽  
J. L. Liong ◽  
A. Miah ◽  
S. Ahmad ◽  
M. Leslie ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Initial Dose ◽  
Performance Status ◽  
Locally Advanced ◽  
Skin Toxicity ◽  
Stage Iii ◽  
Study Cohort ◽  
Neck Carcinoma ◽  
Stage Iii Nsclc ◽  
Grade 3

18032 Background: The addition of cetuximab can increase the efficacy of chemotherapy for advanced NSCLC. Concomitant cetuximab and RT is superior to RT alone for locally advanced squamous cell head & neck carcinoma. The SCRATCH study (cohort I) is a phase I study to assess the safety of synchronous cetuximab and radical RT in patients with Stage III NSCLC. Methods: Cohort I will contain 12 patients with inoperable stage III NSCLC. Inclusion criteria are performance status 0–1, adequate organ function, and disease encompassable within a radical RT volume. Exclusion criteria are previous malignancy, thoracic RT or treatment with EGFR targeted therapy. Patients receive platinum-based induction chemotherapy, followed by weekly intravenous cetuximab (initial dose 400mg/m2; maintenance dose 250mg/m2) and concomitant RT (64Gy/32fractions/45days). The primary end-point is toxicity. NCI Common Toxicity Criteria (CTC) V3.0 assessments are performed weekly during radiotherapy, and at regular follow-up visits. Results: Data from the first 9 patients is available. 2 patients stopped receiving cetuximab early due to toxicity. 1 experienced grade 3 fatigue following the initial dose, and the other declined further treatment after developing grade 2 skin toxicity. 2 patients have died, 1 from disease progression and 1 from thromboembolic disease. Both deaths occurred between months 2 and 4 post RT and were not attributed to the cetuximab therapy. Of the 7 living patients, 2 have survived 1 year (measured from the first day of induction chemotherapy). The maximum NCI CTC V3.0 scores are summarised in the table below. Conclusions: The results suggest that the early and late toxicities of synchronous cetuximab and radical RT are acceptable. Data on all 12 patients will be available by June 2007. SCRATCH Study cohorts II-IV follow on and will recruit sequentially. They will assess the safety of adding concomitant cisplatin (±vinorelbine) to cetuximab and radical RT. [Table: see text] No significant financial relationships to disclose.

First results of induction chemotherapy with cisplatin, docetaxel, and capecitabine for the treatment of nasopharyngeal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Y. Beldjilali ◽  
K. A. Benhadji ◽  
A. Boukerche ◽  
H. Khellafi ◽  
A. Abdelaoui ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Tumor Response ◽  
Performance Status ◽  
Locally Advanced ◽  
High Response Rate ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
P 75 ◽  
Grade 3

6045 Background: The purpose of this phase II study is to assess a new induction chemotherapy regimen combining cisplatin (P), docetaxel (T), and capecitabine (X) in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histological diagnosed locally advanced nasopharyngeal carcinoma (stages III, IVA, and IVB UICC 2002) received induction chemotherapy associating P 75 mg/m2, T 75 mg/m2, both on day 1 and X 1,000 mg/m2/d days 1–14. Cycles were repeated every 3 weeks. A total of 4 cycles was planned for each patient. Induction chemotherapy was followed by concurrent chemo-radiotherapy: P 75 mg/m2 days 1, 22, 42 and radiotherapy (65–70 Gy) 4 to 6 weeks after the fourth cycle of induction treatment. Primary end point was tumor response of the induction regimen. Pts were evaluated according to RECIST criteria by clinical examination and CT scan of the nasopharynx. Results: 40 pts (26 male and 14 female) were enrolled. Median age was 40 years (range 18–56), ECOG performance status was 0–1 in all pts. 30 pts (75%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 10 pts (25%) a poorly differentiated nasopharyngeal carcinoma. 5 pts had stage III disease, 20 pts stage IVA disease and 15 pts stage IVB. Toxicity and tumor response were assessable in 40 pts. After 160 cycles, grade 3–4 toxicities (NCI-CTC 3.0) were: neutropenia (11 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%), and fatigue (10%). No febrile neutropenia was noted. 2 pts had grade 3 renal toxicity and only one patient had hand-foot syndrome (grade 3). Response rates for the 40 pts were: complete response 48%, partial response 40%, stable disease 4%, and progressive disease 8%. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. Outcome of patients after chemoradiotherapy is awaited to evaluate the effectiveness of this new treatment modality. No significant financial relationships to disclose.

Ramucirumab (RAM) for sorafenib intolerant patients with hepatocellular carcinoma (HCC) and elevated baseline alpha fetoprotein (AFP): Outcomes from two randomized phase 3 studies (REACH, REACH2).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4073-4073 ◽  
Author(s):  
Josep M Llovet ◽  
Chia-Jui Yen ◽  
Richard S. Finn ◽  
Yoon-Koo Kang ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Objective Response ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Baseline Characteristics ◽  
Grade 3 ◽  
Ecog Ps ◽  
Require Dose ◽  
Require Dose Adjustment ◽  
Clinical Trial Information

4073 Background: Oral multikinase inhibitors that have shown improvements in overall survival (OS) in HCC are associated with clinically important toxicities that commonly require dose adjustment or discontinuation (D/C) due to intolerance. REACH and REACH-2 studied RAM in patients (pts) with HCC who progressed on or were intolerant to sorafenib (SOR), and REACH-2 only enrolled pts with baseline AFP ≥400 ng/mL. In REACH-2 RAM treatment (trt) improved OS compared to placebo (P), supporting findings in REACH pts with baseline AFP ≥400 ng/mL. An exploratory analysis of outcomes by reason for D/C of SOR was performed. Methods: Pts had advanced HCC, Child-Pugh A, ECOG PS 0-1, and prior SOR. Pts were randomized to RAM 8 mg/kg or P Q2W. A pooled independent pt data analysis (stratified by study) of REACH-2 and REACH pts (AFP ≥400 mg/mL) was performed. Results are reported by reason for SOR D/C (intolerance or disease progression). OS and PFS were evaluated using Kaplan-Meier method and Cox proportional hazard model. Objective response rate (ORR), disease control rate (DCR) and safety are reported. Results: Baseline characteristics in the pooled population were generally balanced between trt arms in each subgroup. Median durations of prior SOR were 2.5 mo for SOR intolerant (n = 70) and 4.0 mo for SOR progressors (n = 472). Median OS (RAM v P) was 10.2 v 6.7 mo for SOR intolerant and 8.0 v 4.7 mo for SOR progressors (Table). Rates of D/C due to trt-related adverse events (AEs) (Table) (7% in each subgroup), and Grade ≥3 AEs (most frequently hypertension) were consistent with those observed in each study. Conclusions: Acknowledging limitations of sample size, the RAM trt benefit in SOR intolerant pts was consistent with that in the ITT population. RAM was well tolerated in SOR intolerant pts with low rates of D/C due to related-AEs. Clinical trial information: NCT01140347, NCT02435433. [Table: see text]

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