Multinational Randomized Phase III Trial With or WithoutConsolidation Chemotherapy Using Docetaxel andCisplatin After Concurrent Chemoradiation in InoperableStage III Non–Small-Cell Lung Cancer: KCSG-LU05-04Jin Seok Ahn, Yong Chan Ahn, Joo-Hang Kim, Chang Geol Lee, Eun Kyung Cho, Kyu Chan Lee, Ming Chen,Dong-Wan Kim, Hoon-Kyo Kim, Young Joo Min, Jin-Hyoung Kang, Jin-Hyuck Choi, Sang-We Kim,Guangying Zhu, Yi-Long Wu, Sung Rok Kim, Kyung Hee Lee, Hong Suk Song, Yoon-La Choi, Jong-Mu Sun,Sin-Ho Jung, Myung-Ju Ahn, and Keunchil Park
Author affiliations appear at the end ofthis article.
Published online ahead of print atwww.jco.org on July 6, 2015.
Supported in part by sanofi-aventisKorea.
Presented in part at the 12th World Confer-ence on Lung Cancer, Seoul, Korea,September 2-5, 2007; the 45th AnnualMeeting of the American Society of ClinicalOncology, Orlando, FL, May 31-June 4,2009, and the 50th Annual Meeting of theAmerican Society of Clinical Oncology,Chicago, IL, May 30-June 3, 2014.
Authors’ disclosures of potential conflictsof interest are found in the article online atwww.jco.org. Author contributions arefound at the end of this article.
Clinical trial information: NCT00326378.
Written on behalf of the Korean CancerStudy Group.
Corresponding author: Keunchil Park,MD, PhD, Division of Hematology-Oncology, Department of Medicine,Samsung Medical Center, Sungkyunk-wan University School of Medicine, 81Irwon-ro, Gangnam-gu, Seoul, 135-710,Korea; e-mail: [email protected].
PurposeTo determine the efficacy of consolidation chemotherapy (CC) with docetaxel and cisplatin (DP)after concurrent chemoradiotherapy (CCRT) with the same agents in locally advanced non–small-cell lung cancer (LA-NSCLC).
Patient and MethodsPatients were randomly assigned to either CCRT alone (observation arm) or CCRT followed by CC(consolidation arm). CCRT with docetaxel (20 mg/m2) and cisplatin (20 mg/m2) was administeredevery week for 6 weeks with a total dose of 66 Gy of thoracic radiotherapy in 33 fractions. In theconsolidation arm, patients were further treated with three cycles of DP (35 mg/m2 each on days1 and 8, every 3 weeks). The primary end point was 40% improvement in progression-free survival(PFS) compared with observation.
ResultsFrom October 2005 to April 2011, 437 patients were randomly assigned. Seventeen patients didnot start CCRT as a result of consent withdrawal or ineligibility reasons after random assignment,leaving 420 patients for this analysis (n � 211 for observation; n � 209 for consolidation). Patientcharacteristics were similar in both arms. In the consolidation arm, 143 patients (68%) receivedCC, of whom 88 (62%) completed three planned cycles. The median PFS was 8.1 months in theobservation arm and 9.1 months in the consolidation arm (hazard ratio, 0.91; 95% CI, 0.73 to 1.12;P � .36). Median overall survival times were 20.6 and 21.8 months in the observation andconsolidation arms, respectively (HR, 0.91; 95% CI, 0.72 to 1.25; P � .44).
ConclusionCC with DP after CCRT with weekly DP in LA-NSCLC failed to further prolong PFS. CCRT aloneshould remain the standard of care.
The incidence of lung cancer is still increasing inmost countries, and it remains the leading causeof cancer death.1,2 Non–small-cell lung cancer(NSCLC) accounts for approximately 80% to 85%of lung cancer. Most patients with NSCLC are de-tected with locally advanced or metastatic diseaseand have poor survival.3
Inoperable locally advanced NSCLC (LA-NSCLC) has shown an approximately 5% 5-yearsurvival rate with radiation therapy (RT) alone.4 Forthe treatment of LA-NSCLC, multidisciplinary ther-
apy has resulted in survival improvements. In the1980s, induction chemotherapy was investigated forLA-NSCLC, and several randomized phase III stud-ies of induction chemotherapy and subsequent RThave reported significant increases in survival.5-7 In the1990s, a new approach with the concurrent adminis-tration of chemotherapy and RT was introduced anddemonstrated further improvements in survival com-pared with RT alone.8-10 Subsequent randomizedphase III trials have confirmed the superiority of con-current chemoradiotherapy (CCRT) compared withsequential chemoradiotherapy.11,12 Since then, thestandard of care for LA-NSCLC has been CCRT.
JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T
Despite this progress with a combined-modality approach, theprognosis of LA-NSCLC remains poor, with a median survival time of15 to 18 months.13 In 2003, the Southwest Oncology Group 9504 trial,a phase II trial for consolidation chemotherapy (CC) with docetaxelafter CCRT with etoposide and cisplatin (EP), reported promisingresults with a median progression-free survival (PFS) of 16 monthsand a median survival of 26 months.14
In a previous phase II study of CCRT with CC with oral etoposideand cisplatin for LA-NSCLC, we reported promising response ratesand survival results.15 We also conducted a phase I study of weeklydocetaxel and cisplatin (DP) concurrent with thoracic RT in stage IIINSCLC16 and confirmed the feasibility of this regimen with acceptabletoxicities. On the basis of these studies, this phase III randomized trialwas designed to evaluate whether CC with these same third-generation chemotherapeutic agents after CCRT with weekly DP pro-vides survival benefit for patients with inoperable stage III NSCLC.
PATIENTS AND METHODS
Patients with histologically documented NSCLC with inoperable stage IIIA orIIIB disease, which was proven by computed tomography (CT), magneticresonance imaging, and/or positron emission tomography (PET), were eligi-ble. N2 or N3 disease must have been confirmed by pathology or PET. Patientswere age 18 years or older and had an Eastern Cooperative Oncology Groupperformance status of 0 to 1 at baseline.
Eligible patients also met the following criteria: measurable disease basedon RECIST; no prior chemotherapy, RT to the chest, immunotherapy, orbiologic therapy; forced expiratory volume in 1 second � 0.8 L by spirometry;and adequate bone marrow, renal, and hepatic function. Female patients werealso excluded if they were pregnant or lactating, had not taken a pregnancy testwithin 14 days before the first administration, or had childbearing potentialand were not willing to use adequate contraception.
All patients provided written informed consent. The study was approvedby the institutional review board of every participating institution and wasperformed in accordance with the Declaration of Helsinki and the Interna-tional Conference on Harmonization/Good Clinical Practice.
Study Design and Treatment
This was an international, multicenter, open, randomized, phase IIIstudy to evaluate the effects of CC of DP after CCRT in patients with inoper-able LA-NSCLC. Random assignment was performed through a computer-ized online system. The stratification factors were participating center andperformance status.
Eligible patients received docetaxel 20 mg/m2 intravenously and cis-platin 20 mg/m2 intravenously on days 1, 8, 15, 22, 29, and 36. All patientsreceived thoracic RT 5 days per week in once-daily fractions and at 2.0 Gyper fraction. The total dose was 66 Gy in 33 fractions. The initial 46 Gy orRT over 23 fractions covered the clinical target volume plus the margin,and the later 20 Gy over 10 fractions covered the gross tumor volume plusthe margin. CC was conducted between 4 and 8 weeks after the completionof CCRT in patients with no local progression or distant metastases andadequate organ function before the start of CC. On days 1 and 8 of eachcycle, an intravenous infusion of docetaxel 35 mg/m2 for 1 hour, followedby cisplatin 35 mg/m2 for 1 hour, was given. This regimen was repeatedevery 3 weeks and continued for up to three cycles as long as there was nounacceptable toxicity or evidence of disease progression.
History and physical examination, assessment of Eastern CooperativeOncology Group performance status, pulmonary function tests includingforced expiratory volume in 1 second, CBC, serum chemistries, and chest CTwere obtained at baseline. PET scans were mandated except for in T4 disease.Brain CT or magnetic resonance imaging was mandatory at baseline.Throughout the CCRT phase, CBC was obtained weekly and serum chemis-
tries were obtained every 3 weeks. Baseline CBC and serum chemistries wereobtained and repeated before each cycle during the consolidation phase in allpatients. Evaluation of response by chest CT was first carried out within 4 to 6weeks after the completion of CCRT, then within 9 to 12 weeks after the firsttumor assessment, and continued every 3 months for the first 3 years, every 6months for years 3 to 5, and yearly thereafter. Adverse events were collectedfrom the first administration of the study drug to 30 days after the last admin-istration. The incidence of pneumonitis was observed for up to 1 year after thecompletion of treatment.
Statistical Analysis
The primary objective was to show that the consolidation arm wouldincrease the median PFS by 40% from the PFS of 12 months reported fromobservation by Park et al.15 PFS was defined as the time from random assign-ment to the first documentation of disease progression or death, whichevercame first. With a total of 434 patients (n � 217 per arm), we had 90% powerby the log-rank test with a two-sided � � .05. The sample size calculation wasbased on the following assumptions: 10% of attrition, 18 months of additionalfollow-up, and an annual accrual of 72 patients. A preplanned interim analysisafter 50% of enrollment demonstrated no safety issues and was previouslyreported in 2009.17
The secondary end points included a comparison of overall survival(OS), overall response rate, patterns of failure, and toxicities between the twoarms. Adverse events were graded according to the Common TerminologyCriteria for Adverse Events version 3.0. Descriptive statistics used medians orproportions with their appropriate measures of distribution. The Kaplan-Meier method was used to estimate the distribution of PFS and OS, and thedistribution of each end point was compared between the two treatment armsusing the log-rank test. Univariable and multivariable regression analyses wereconducted on PFS using the Cox regression method. All P values are two-sided. We considered P � .05 to be significant. The exploratory end point wasto investigate the correlation of tissue expression of ERCC1 and class III�-tubulin with the clinical outcome.
Exploratory Biomarker Study
Formalin-fixed, paraffin-embedded, 4 �m-thick tissue sections werelabeled with mouse monoclonal anti-ERCC1 antibody (8F1; GeneTex, Irvine,CA) and anti–�3-tubulin antibody (TU-20; Santa Cruz Biotechnology, SantaCruz, CA). Immunostaining was performed using a Bond-max autoimmu-nostainer with Bond Polymer refine detection, DS9800 (Leica Biosystems,Melbourne, Australia). Immunohistochemical evaluation was performed by apathologist without knowledge of the clinical data. Tumor staining intensitywas graded on a scale of 0 to 3 using adjacent nonmalignant cells as a reference(intensity of 2). One hundred to 1,500 positive or negative tumor cells perspecimen were counted manually. The percentage of positive tumor cells wascounted for each specimen. This proportional percentage was multiplied bythe staining intensity to obtain a final semiquantitative H score (Appendix FigA1, online only).
RESULTS
Between October 2005 and April 2011, 459 patients from 31 centers inKorea, China, and Taiwan were screened for the study. Among them,437 patients were eligible and were allocated to the observation arm(n � 219) or consolidation arm (n � 218). Eight patients from theobservation arm and nine patients from the consolidation arm did notstart CCRT because of consent withdrawal or ineligibility reasons,leaving 420 patients in the study (n � 211 for observation; n � 209 forconsolidation). These 420 patients were included in the final analysiscohort (Fig 1). Patient characteristics are listed in Table 1. Approxi-mately half of the patients had adenocarcinoma histology, and ap-proximately 80% had stage IIIB disease. Demographic baselinecharacteristics were well balanced between the two groups.
Consolidation Docetaxel and Cisplatin in Stage III NSCLC
Of the 209 patients randomly assigned to the consolidationarm, 42.1% received all of the three planned cycles, and 54.1%finished at least two cycles (Table 2). Sixty-six patients (31.6%) didnot receive any CC. The reasons for not receiving CC includedearly death (n � 22), consent withdrawal or patient refusal (n �
14), adverse events of CCRT (n � 12), disease progression (n �10), and other reason (n � 8).
Efficacy
With a median follow-up time of 50.7 months, there were 349events in total, 180 in the observation arm and 169 in the consolida-tion arm. There was no difference in PFS between the two arms, witha median PFS of 8.1 months (95% CI, 7.6 to 8.9 months) in theobservation arm and 9.1 months (95% CI, 7.9 to 10.9 months) in theconsolidation arm (hazard ratio [HR], 0.91; 95% CI, 0.73 to 1.12; P �.36; Fig 2A). In subgroup analysis, none of the factors except age (� 60years old) were significant (Appendix Fig A2, online only).
There were 279 deaths, 145 in the observation arm and 134 in theconsolidation arm. Median OS also did not differ between the twoarms, with a median OS of 20.6 months (95% CI, 17.6 to 26.3 months)in the observation arm and 21.8 months (95% CI, 17.7 to 24.7months) in the consolidation arm (HR, 0.91; 95% CI, 0.72 to 1.25; P�.44; Fig 2B).
The overall response rate was 38.4% (with 4.3% complete re-sponse) in the observation arm versus 43.1% (with 2.9% completeresponse) in the consolidation arm without a significant difference
(P � .33). The disease control rate was approximately 58% in botharms (Appendix Table A1, online only).
At the time of this analysis, the sites of treatment failure wereknown in approximately half of the patients. Both arms showed sim-ilar locoregional or distant failure rates with no significant differences.The remaining or contralateral lung was the most common site of thefirst relapse followed by the brain, pleura, bone, and liver (AppendixTable A2, online only).
Safety
During the CCRT phase, the hematologic toxicities were as ex-pected. In patients assigned to the consolidation arm, there wasslightly more febrile neutropenia and grade 3 or 4 neutropenia (Table3). Table 4 lists the nonhematologic toxicities. During the CCRTphase, esophagitis was observed in 79% of patients with 9.5% grade 3or 4 toxicities. Grade 3 or 4 infections developed in 6.4% of patientswith some treatment-related mortality (TRM). Radiation pneumoni-tis was less frequently observed, but one patient died of radiationpneumonitis. During the consolidation phase, 2.3% of patients expe-rienced grade 3 or 4 infection, and 1.2% of patients had grade 3 or 4radiation pneumonitis with some ensuing TRM. The overall TRMrate was 3.6% during the CCRT phase and 2.9% during the consoli-dation phase.
Exploratory Biomarker Study
The median H scores for ERCC1 (n � 97) and class III �-tubulin(n � 97) were 240 and 30, respectively. ERCC1 expression had no
significant correlation with PFS or OS (P � .40 and P � .53, respec-tively). Class III �-tubulin expression was also not correlated with PFSor OS (P � .97 and P � .44, respectively).
DISCUSSION
Most studies that have investigated the role of CC after CCRT havebeen small phase I/II trials; few large randomized phase III trials havebeen conducted. In each trial, there have been differences in patientcharacteristics, CCRT backbones, or CC regimens, and none of thetrials were designed for a specific subset of patients by incorporatingmolecular biomarkers.18 Our randomized phase III trial, which is thelargest reported to date, failed to demonstrate that CC with DP aftercompleting CCRT with the same agents improved survival. This is inline with a recent report on the pooled analysis of 41 studies, whichfailed to provide evidence that CC yield significant survival benefit forpatients with LA-NSCLC.19
While this study was being conducted, a phase III study by theHoosier Oncology Group (HOG), which included 203 patients usingsingle-agent docetaxel as CC after CCRT, was prematurely terminatedas a result of futility analysis. Compared with the HOG study, we hadstricter criteria for N2 or N3 disease, which needed to be proven bypathology or PET. More patients were staged by PET in our study thanin the HOG study (92% v 67%, respectively). The most striking dif-ference in study design was the random assignment point. Our pa-tients were randomly assigned before the start of CCRT. We thought
Patients Events mPFS (95% CI)
CCRT alone 211 180 8.05 (7.56 to 8.90)CCRT + consolidation 209 169 9.10 (7.92 to 10.94)
Patients Events mOS (95% CI)
CCRT alone 211 145 20.63 (17.58 to 26.28)CCRT + consolidation 209 134 21.78 (17.71 to 24.74)
CCRT aloneCCRT + consolidation
Hazard ratio = 0.906(95% CI, 0.734 to 1.119)P = .410
Prog
ress
ion-
Free
Sur
viva
l(p
ropo
rtion
)
Time (months)
1.0
0.8
0.6
0.4
0.2
BA
0 36 482412 60 72 84
CCRT aloneCCRT + consolidation
Hazard ratio = 0.911(95% CI, 0.720 to 1.253)P = .438
Over
all S
urvi
val
(pro
porti
on)
Time (months)
1.0
0.8
0.6
0.4
0.2
0 36 482412 60 72 84
Fig 2. (A) Progression-free survival. (B) Overall survival. CCRT, concurrent chemoradiotherapy; mOS, median overall survival; mPFS, median progression-freesurvival.
this would result in minimal data loss and less bias. We used DP duringCCRT instead of the more common regimen of EP to investigatewhether these newer agents were any superior to older ones. Docetaxelhas been tested in CCRT with cisplatin in many phase I/II trials withpromising response rates,16,20-22 and a recent phase III trial showedthat CCRT with DP had better efficacy in the early follow-up period.23
We also used a DP doublet in the consolidation phase to maximize theeffects of additional treatment.
The major obstacle in this trial was that many patients could notcomplete the three planned cycles of CC, as in other trials.19 Approx-imately one third of the patients (32%) did not even start CC, and onlyapproximately half of the patients could complete � two cycles of CC.Approximately half of the patients failed to start CC because of diseaseprogression or death before the consolidation phase. Another majorreason was related to incomplete recovery from the adverse effects ofCCRT. A full-dose doublet regimen of CC in our trial might havefurther reduced the rate of completing the three planned cycles of CC.
Hematologic toxicities during both the CCRT and consolidationphases were not so severe, perhaps because of the weekly administra-tion of DP. Several phase III trials and a meta-analysis of weeklydocetaxel as second-line chemotherapy for advanced NSCLC showedsignificant benefit in grade 3 to 4 neutropenia compared with admin-istering docetaxel every 3 weeks.24-27 Nonhematologic toxicities dur-ing the CCRT phase were as expected and similar to conventionalCCRT with EP. In brief, CCRT with weekly DP is a feasible regimenwith acceptable toxicities.
It is of interest that there was a significant benefit with CC forpatients older than age 60 years (HR, 0.72). In a population-basedstudy from National Cancer Institute’s Surveillance, Epidemiology,and End Results database in elderly patients with LA-NSCLC, CCRTalone is associated with the greatest mortality risk compared witheither induction chemotherapy or CC with CCRT, suggesting thatmore gradual strategies may be more appropriate for the elderly pop-ulation.28 In addition, in the combined analysis of five Cancer andLeukemia Group B trials, age was not an independent predictive factorof outcome.29 However, the exact reason why patients older than age60 benefited in this study remains unexplained. There was no differ-ence in baseline characteristics between patients older than 60 andpatients � 60 years.
ERCC1 is a component of the nucleotide excision repair path-way, which is essential for the repair of platinum-DNA adducts and isassociated with cellular resistance to platinum compounds. LowERCC1 expression has been correlated with superior PFS and OS inpatients with advanced NSCLC treated with cisplatin.30-32 In a small-scale retrospective study, immunohistochemistry for ERCC1 was use-ful for predicting survival in patients with LA-NSCLC receiving CCRTwith DP.33 The International Adjuvant Lung Cancer Trial Collabora-tive Group has demonstrated a survival benefit with adjuvantcisplatin-based chemotherapy in patients whose tumors were negativefor ERCC1 expression.34 However, the ERCC1 immunohistochemis-try results were not reproducible.35,36 Small comparative studies havealso shown that overexpression of class III �-tubulin is correlated withresistance to tubulin-binding agents, taxanes, and vinorelbine and hasresulted in poor prognosis in metastatic NSCLC.37-39 In contrast, highlevels of class III �-tubulin were associated with an adverse prognosisbut also seemed to be associated with increased benefit from adju-vant cisplatin/vinorelbine chemotherapy in patients with operableNSCLC.40 In our exploratory biomarker study, the expression ofERCC1 and class III �-tubulin was not correlated with either PFS orOS. Until now, no biomarker has been validated to predict benefit orresistance to currently available cytotoxic chemotherapy.41
Given that almost half of the patients could not receive CC afterCCRTasaresultofearlyprogressionand/ortoxicities,weneedtodevelopbetter tolerated regimens without the loss of efficacy. Several new agentsare under investigation. PROCLAIM, a phase III study of pemetrexed,cisplatin,andRTfollowedbyconsolidationpemetrexedversusEPandRTfollowed by a CC of choice in patients with stage III NSCLC of nonsqua-mous histology, was prematurely terminated based on the planned in-terim futility analysis.42 The role of cetuximab is being evaluated in theRadiation Therapy Oncology Group 0617 trial, which randomly assignedpatients to standard-dose or high-dose RT or carboplatin and paclitaxelalone,withorwithoutcetuximabconcurrentwithRT.Theinferiorresultsof high-dose RT were already presented, and the effect of cetuximabawaits further follow-up.43 L-BLP25 is a MUC1 antigen-specific cancerimmunotherapy. A phase III trial (START [Stimulating Targeted Anti-genic Response to Non-Small-Cell Lung Cancer]) investigating L-BLP25in patients who have finished CCRT was completed. L-BLP25 mainte-nance therapy, however, did not significantly prolong OS.44 Given the
highlocoregional failureandthepresenceofdistantmetastases,newerRTtechniquesareneededincludinghypofractionation, stereotacticbodyRT,adaptive RT, or proton therapy.
In summary, this study confirms that the current strategy ofconsolidation treatment with cytotoxic chemotherapy after CCRTdoes not improve survival in patients with LA-NSCLC. In future trials,CCRT without CC should remain the reference arm. Given that dis-tant failure is the most common pattern of failure after CCRT inLA-NSCLC and the treatment outcome remains poor, we stronglybelieve that the concept of consolidation therapy needs to be furtherexplored using less toxic, better tolerated agents.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTSOF INTEREST
Disclosures provided by the authors are available with this article atwww.jco.org.
AUTHOR CONTRIBUTIONS
Conception and design: Jin Seok Ahn, Yong Chan Ahn, Hoon-Kyo Kim,Sin-Ho Jung, Myung-Ju Ahn, Keunchil ParkProvision of study materials or patients: Jin Seok Ahn, Yong Chan Ahn,Joo-Hang Kim, Chang Geol Lee, Eun Kyung Cho, Kyu Chan Lee, MingChen, Hoon-Kyo Kim, Young Joo Min, Jin-Hyoung Kang, Jin-HyukChoi, Sang-We Kim, Yi-Long Wu, Sung Rok Kim, Kyung Hee Lee, HongSuk Song, Jong-Mu Sun, Myung-Ju Ahn, Keunchil ParkCollection and assembly of data: Jin Seok Ahn, Yong Chan Ahn,Joo-Hang Kim, Chang Geol Lee, Eun Kyung Cho, Kyu Chan Lee, MingChen, Dong-Wan Kim, Hoon-Kyo Kim, Young Joo Min, Jin-Hyuk Choi,Sang-We Kim, Guangying Zhu, Yi-Long Wu, Sung Rok Kim, Kyung HeeLee, Hong Suk Song, Myung-Ju Ahn, Keunchil ParkData analysis and interpretation: Jin Seok Ahn, Yong Chan Ahn,Dong-Wan Kim, Jin-Hyoung Kang, Yi-Long Wu, Yoon-La Choi,Jong-Mu Sun, Sin-Ho Jung, Myung-Ju Ahn, Keunchil ParkManuscript writing: All authorsFinal approval of manuscript: All authors
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Affiliations
Jin Seok Ahn, Yong Chan Ahn, Yoon-La Choi, Jong-Mu Sun, Myung-Ju Ahn, and Keunchil Park, Samsung Medical Center,Sungkyunkwan University School of Medicine; Joo-Hang Kim and Chang Geol Lee, Yonsei Cancer Center, Yonsei University Health System;Dong-Wan Kim, Seoul National University Hospital; Jin-Hyoung Kang, Catholic University Seoul St Mary’s Hospital; Sung Rok Kim, InjeUniversity Sanggye Paik Hospital; Sang-We Kim, Asan Medical Center, University of Ulsan College of Medicine; Sin-Ho Jung, SamsungMedical Center, Office of Biomedical Science, Seoul; Eun Kyung Cho and Kyu Chan Lee, Gachon University Gil Medical Center, Incheon;Hoon-Kyo Kim, Catholic University St Vincent’s Hospital; Jin-Hyuck Choi, Ajou University Hospital, Suwon; Young Joo Min, UlsanUniversity Hospital, Ulsan; Kyung Hee Lee, Yeungnam University Medical Center; Hong Suk Song, Keimyung University Dongsan MedicalCenter, Daegu, Korea; Ming Chen, Sun Yat-Sen University Cancer Center, Guangzhou; Guangying Zhu, Beijing Cancer Hospital, Beijing; Yi-Long Wu, Guandong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangdong,China.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Multinational Randomized Phase III Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After ConcurrentChemoradiation in Inoperable Stage III Non–Small-Cell Lung Cancer: KCSG-LU05-04
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships areself-held unless noted. I � Immediate Family Member, Inst � My Institution. Relationships may not relate to the subject matter of this manuscript. For moreinformation about ASCO’s conflict of interest policy, please refer to www.asco.org/rwc or jco.ascopubs.org/site/ifc.
Jin Seok AhnHonoraria: Eli Lilly, Pfizer, Roche
Yong Chan AhnNo relationship to disclose
Joo-Hang KimResearch Funding: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer
Chang Geol LeeNo relationship to disclose
Eun Kyung ChoConsulting or Advisory Role: Celltrion
Kyu Chan LeeNo relationship to disclose
Ming ChenNo relationship to disclose
Dong-Wan KimConsulting or Advisory Role: Novartis
Hoon-Kyo KimNo relationship to disclose
Young Joo MinNo relationship to disclose
Jin-Hyoung KangNo relationship to disclose
Jin-Hyuk ChoiNo relationship to disclose
Sang-We KimNo relationship to disclose
Guangying ZhuNo relationship to disclose
Yi-Long WuHonoraria: AstraZeneca, Eli Lilly, Pfizer, Roche
Sung Rok KimNo relationship to disclose
Kyung Hee LeeNo relationship to disclose
Hong Suk SongNo relationship to disclose
Yoon-La ChoiNo relationship to disclose
Jong-Mu SunNo relationship to disclose
Sin-Ho JungNo relationship to disclose
Myung-Ju AhnNo relationship to disclose
Keunchil ParkHonoraria: Astellas Pharma, AstraZeneca, AVEO, Clovis Oncology, EliLilly, Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, RocheConsulting or Advisory Role: Astellas Pharma, AstraZeneca, AVEO,Boehringer Ingelheim, Clovis Oncology, Daiichi Sankyo, Eli Lilly,Hanmi, Kyowa Hakko Kirin, Novartis, Ono Pharmaceutical, RocheSpeakers’ Bureau: Eli LillyResearch Funding: AstraZeneca, Sanofi
Consolidation Docetaxel and Cisplatin in Stage III NSCLC
Abbreviation: CCRT, concurrent chemoradiotherapy.�Select sites; multiple sites in some patients.
A B
DC
Fig A1. Immunohistochemical staining of ERCC1 and class III �-tubulin protein in lung cancer tissues. Examples of the expression of each protein are shown. (A)ERCC1 H score of 300. (B) ERCC1 H score of 40. (C) Class III �-tubulin H score of 280. (D) Class III �-tubulin H score of 20.
