- Allen Chan
- Anthony T. Chan
- Joseph Wee
LBA6 - First-line cetuximab plus cisplatin and fluorouracil vs cisplatin and fluorouracil in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: The randomized, phase III CHANGE-2 trial
- Ye Guo
- Ye Guo
- Yi Luo
- Qingyuan Zhang
- Xiaoming Huang
- Zhengdong Li
- Liangfang Shen
- Jifeng Feng
- Yan Sun
- Kunyu Yang
- Ming-hua Ge
- Xiaodong Zhu
- Lin Wang
- Yanyan Liu
- Xiaohui He
- Chunmei Bai
- Kai Xue
- Yan Zeng
- Yuanyuan Cao
- Wenfeng Chen
- Tongyu Lin
Abstract
Background
The EXTREME regimen (cetuximab + platinum + 5-FU up to 6 cycles followed by cetuximab maintenance until progression) is the global gold standard of care for 1L R/M SCCHN. However, this regimen is not yet approved in China. In the phase III EXTREME trial, adding cetuximab to platinum-based therapy (PBT) had significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) vs PBT alone. The multicenter, randomized, open-label, phase III CHANGE-2 trial assessed the efficacy and safety of a modified EXTREME vs cisplatin-based therapy (cisplatin + 5-FU or “CBT”) alone for the 1L treatment of Chinese patients with R/M SCCHN for the purpose of registration in China.
Methods
Chinese patients with R/M SCCHN, performance status of 0 or 1, and with no prior systemic chemotherapy for R/M disease received CBT ± cetuximab for up to 6 cycles, followed by cetuximab maintenance for patients in the cetuximab arm who had at least stable disease at the end of the chemotherapy phase. The primary endpoint was PFS time assessed by independent review committee (IRC).
Results
243 patients (164 in the cetuximab + CBT arm and 79 in the CBT arm) were enrolled; 23% and 22% of patients, respectively, were ≥ 65 years old. The HR for PFS by IRC was 0.57 (95% CI, 0.40-0.80) in favor of cetuximab + CBT (median: 5.5 vs 4.2 months). ORR by IRC was 50% vs 27% in the cetuximab + CBT vs CBT arm, respectively. At the time of analysis, there had been 159 OS events (65%). The HR for OS was 0.75 (95% CI, 0.53-1.04) in favor of cetuximab + CBT (median: 10.2 vs 8.9 months). 68% and 59% of patients in the cetuximab + CBT vs CBT arm experienced a grade ≥ 3 adverse event (AE), respectively. Lung infection was the most frequent serious AE (SAE) in both arms (3.7% and 5.3%, respectively); 7.4% of patients in the cetuximab arm experienced a cetuximab-related SAE.
Conclusions
The CHANGE-2 trial showed that the addition of cetuximab to CBT improves median PFS, median OS and ORR vs CBT alone with no unexpected safety findings and confirms cetuximab + CBT as the 1L standard of care for patients with R/M SCCHN.
Editorial acknowledgement
ClinicalThinking, funded by Merck KGaA, Darmstadt, Germany.
Clinical trial identification
EMR062202-060
Legal entity responsible for the study
Merck KGaA.
Funding
Merck KGaA.
Disclosure
Y. Zeng, Y. Cao, W. Chen: Merck Serono, Beijing, China. All other authors have declared no conflicts of interest.
Discussion
304O - Relationship of Circulating Tumor Cells to Progression-Free Survival and Tumor Response in Patients with Metastatic Nasopharyngeal Carcinoma: A Prospective Cohort Study
- Rui You
- Rui You
- Mingyuan Chen
- You-Ping Liu
- Yi-Nuan Zhang
- Pei-Yu Huang
Abstract
Background
To investigate and compare circulating tumor cells (CTCs) with Epstein-Barr virus DNA (EBV DNA) in noninvasive diagnosis, monitoring, and outcome prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC).
Methods
We prospectively enrolled 148 mNPC patients and 122 non-metastatic NPC patients, between December 2014 and August 2016. The levels of CTCs and EBV DNA were measured before the patients were due to start established chemotherapy and at the first follow-up visit. 281 mNPC patients recruited from January 2011 to December 2014 formed independent validation cohort for EBV DNA. The progression of the disease and the response to treatment were determined by standard imaging studies at participating centers.
Results
In 270 prospectively recruited NPC patients, we observed improved specificity (86.0% vs 51.0%) of CTC levels as compared with EBV DNA copy number. 148 mNPC patients were stratified into two categories based on cutoff points of 12 in CTCs and 10000 in EBV DNA copy number. The cutoff point of 10000 in EBV DNA was confirmed in independent validation cohort. Baseline CTC level of 12 remained an independent prognostic factor of progression-free survival (PFS), but not EBV DNA. The median PFS was significantly longer for patients with CTC level of 0 at first follow-up compared with that of patients with CTC levels of > 1 at first follow-up regardless of CTC levels at baseline (P < 0.05). Among non-progressing patients, the PFS with complete/partial response and CTC level of 0 at first follow-up was significantly longer compared with rest of the patients (P < 0.05).
Conclusions
Our data demonstrated an important role of CTC determination in mNPC patients.
Clinical trial identification
NCT02505139.
Legal entity responsible for the study
Sun Yat-sen University Cancer Center.
Funding
The National Natural Science Foundation of China (No.81572912, 81772895, 81572848, and 81772877), Guangdong Public Welfare Research and Capacity Building Projects (2014B020212005), the Program of Sun Yat-sen University for Clinical Research 5010 Program (No.201310), the Major Project of Sun Yat-sen University for the New Cross Subject, the Special Support Program for High-level Talents in Sun Yat-sen University Cancer Center (to M.Y. Chen), and the National Key Research and Development Program of China (2016YFC0905000), Guangdong Province Science and Technology Development Special Funds (Frontier and Key Technology Innovation Direction – Major Science and Technology Project), Guangzhou Science and Technology Planning Project - Production and Research Collaborative Innovation Major Project.
Disclosure
All authors have declared no conflicts of interest.
Discussion led by moderators
305O - Surgery for Isolated Regional Failure in Nasopharyngeal Carcinoma after Radiation: Selective or Comprehensive Neck Dissection
- Liu You-Ping
- Liu You-Ping
- Rui You
- Mingyuan Chen
- H Li
Abstract
Background
To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure.
Methods
A total of 294 rT0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-sen University Cancer Center between January 1984 and February 2014 were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS).
Results
Both univariate and multivariate analyses showed that SND was not inferior to CND (p > 0.05), but demonstrated that extracapsular spread (ECS) (HR 3.49, 95% CI 2.30–5.29, P < 0.001), rN stage (HR 1.96, 95% CI 1.29–2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40–5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively).
Conclusions
With a similar radical dissection extent around the tumor, rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC.
Legal entity responsible for the study
YP Liu, MY Chen.
Funding
National Natural Science Foundation of China.
Disclosure
All authors have declared no conflicts of interest.
Discussion led by moderator
- Joseph Wee
- Joseph Wee
307O - Randomized, double-blind, placebo-controlled trial of probiotics to reduce radiation and chemotherapy induced oral mucositis for nasopharyngeal cancer patients
- Chunling Jiang
- Chunling Jiang
- Honghui Xie
- Lei Zeng
- Tingtao Chen
- Jingao Li
Abstract
Background
To determine the effect of probiotic combination on radiation-induced oral mucositis in nasopharyngeal cancer (NPC) patients with concurrent chemoradiotherapy.
Methods
A randomized, double-blind, placebo-controlled trial was conducted in Jiangxi Cancer Hospital between May 2017 to December 2017. Eligible patients (N = 120, 18-70 years old) with pathologically diagnosed locally advanced nasopharyngeal carcinoma with concurrent chemoradiotherapy were randomly assigned (computer-block; 2:1) to receive probiotic combination or placebo at the initiation of chemoradiotherapy. The primary endpoints were III oral mucositis incidence, and the occurrence of oral mucositis, tumor response, immune function, and microbial diversity of intestinal microbiota were monitored and analyzed.
Results
We found that patients taking probiotic combination showed significant reduction of oral mucositis (1.35 vs. 2.47, p < 0.001), while the tumor response was similar to the patients in the control group (0.885 vs. 0.875, p > 0.999). Further, we found that the radiotherapy + chemotherapy had greatly lowered the number of immune cells, while probiotic combination markedly lowered the reduction rate of autologous cells of CD4+T cells (76.59% vs. 52.85%, p < 0.05), CD8+T cells (62.94% vs. 29.76%, p < 0.05) and CD3+T cells (69.72% vs. 45.49, p < 0.05) in ARCPC (after the treatment of RT + CR + probiotic combination) group. High-throughput sequencing results indicated that RT had obviously disturbed the intestinal diversity of patients in ARCP (after the treatment of RT + CR + placebo) group, while uptake of probiotic combination markedly restored the microbial diversity in ARCPC towards to HP (healthy people) group and BRCPC (before the treatment of RT + CR + probiotic combination) group.
Conclusions
Our results indicate that probiotic combination significantly enhance the patients' immune response and reduce the incidence of oral mucositis through modification of gut microbiota.
Editorial acknowledgement
This work was supported by grants from the National Natural Science Foundation of China (No. 81760547, 81503364, 31560264)
Clinical trial identification
NCT03112837.
Legal entity responsible for the study
Jiangxi Cancer Hospital.
Funding
Grants from the National Natural Science Foundation of China (No. 81760547, 81503364, 31560264).
Disclosure
All authors have declared no conflicts of interest.