進行・再発非小細胞肺癌(NSCLC)初回化学療法終了後患者の維持療法・二次療法実施に関する観察研究、
中間報告

10079

堀田 勝幸1，木浦 勝行1，葉 清隆2，内藤 陽一2 ，岸 一馬3，後藤 悌4，大橋 靖雄5，國頭 英夫6

岡山大学病院 呼吸器内科1，国立がん研究センター東病院2，虎の門病院 呼吸器センター内科・臨床腫瘍科3，
東京大学大学院医学系研究科 呼吸器内科学4，東京大学大学院医学系研究科 公共健康医学専攻5，
三井記念病院 呼吸器内科6Comprehensive
SupportProjectUMIN#000006393

BackgroundResults

Standard care of advanced NSCLC• First-line platinum-based chemotherapy(first-line CT)• Second-line chemotherapy (second-line CT)
after the progression of the first-line CT
Maintenance therapy after the first-line CT• Recently, maintenance therapy has beenreported to be beneficial.
• Its impact on overall survival appears to be
marginal or negligible, when most patients
could receive timely active second-line CT
after progression.

• A total of 865 eligible patients with advanced NSCLC provided patient characteristics and details of the first-line
CT.
• At the time of cut off, 800 patients were assessable for response of the first-CT. A total of 572 patients had
CR/PR/SD.
• Administration of the second-CT was analyzed for 506 patients who had progression after first-line CT(primary study population)• Maintenance therapy was administered to 144 patients. Of those,• 7 patients did not progress.
• of 137 patients progressed, 25 patients (18.2%) could not receive second-line CT.
• Observation with no maintenance therapy was done in 362 patients. Of those,• 50 patients did not progress.
• of 312 patients progressed, 79 patients (25.3%) could not receive second-line CT.
• Decline of PS was the principal reason for not receiving second-line CT in both patients with and withoutmaintenance CT.

ObjectiveFigure 1• To investigate the proportion of patients
who had progression during observation
after CR/PR/SD of first-line CT actually
received the second-line CT• To elucidate factors associated with secondline CT administration in advanced NSCLC
patients.

Advanced NSCLC patients with first-line platinum CT(n=865)
Data collecting (n=65)
Accessible for response (n=800)

Methods

PD/NE=162/66

Study design• Cohort (prospective observational) study
Primary endpoint• Proportion of patients who received
second-line CT after first-line CTPatient inclusion• Patients with advanced NSCLC who received
platinum-based first-line CT• From April 2010 to September 2011, at 30
institutions in Japan
Data collection• Baseline characteristics (age, gender, ECOGPS, smoking status, comorbidities, bodymass index, histological subtype, EGFR/ALKstatus, CBC/chemistry at registration)• Regimens and responses to thefirst/second/third-line CT(regimen, response)• Administration of maintenance CT• Reason for not receiving second-line CT(if it was not administered)• Survival
Data cutoff• Interim report describing patients with atleast 6 months of follow up at April 2012
Support• Supported by the Public Health ResearchCenter Foundation CSPOR

Conclusions• Preliminary results of this large observational
study in Japan suggested that
• Among the patients who did not received
maintenance therapy, 25.3% missed an
opportunity to receive appropriate
second-line CT.
• We could not find associated factors for
not receiving second-line CT.
• As for the patients who received
maintenance therapy, 18.2% did notreceive second-line CT.
• Administration of maintenance therapy
did not appear to compromise the chance
to receive second-line CT.
• Further investigation is needed to identify thepatients who would be less likely to receive
the second-CT after disease progression, andthus would be more likely to receive benefit
from maintenance therapy strategy.

CR/PR/SD=4/272/296 (n=572)
Data collecting (n=51)
Data missing (n=15)
Primary study population (n=506)
Observation(no maintenance therapy)(n=362)This study was funded by Comprehensive Support Project forOncology Research (CSPOR) of Public Health Research Foundation. We
would like to thank patients, their families, and following institutions;
Hokkaido University Hospital, KKR Sapporo Medical Center, Iwate
Prefectural Central Hospital, Tohoku University Hospital, Universityof Tsukuba, Ibaraki Prefectural Central Hospital, Tochigi Cancer
Center, Gunma Prefectural Cancer Center, Saitama Medical
University International Medical Center, Saitama Cancer Center,
Tokyo Metropolitan Cancer and Infectious Diseases Center
Komagome Hospital, The Cancer Institute Hospital Of JFCR,
Japanese Red Cross Medical Center, Kitasato University Hospital,
Kanagawa Cardiovascular and Respiratory Center, Fujisawa City
Hospital, Shinshu University Hospital, Nagoya University GraduateSchool Of Medicine, Okayama University Hospital, Hiroshima
Prefectural Hospital, Kurume University School of Medicine,Nagasaki University Hospital, Mitsui Memorial Hospital, Universityof Tokyo Hospital, National Cancer Center Hospital East,Toranomon Hospital, Nishigunma National Hospital, NTT MedicalCenter Tokyo, Teikyo University School of Medicine, National
Center for Global Health and Medicine

Second-line therapy yes/no(n=233/79)□受託 ■寄付 □科学研究費 □その他(財源の供給元

公益財団法人パブリックヘルスリサーチセンター

発表者氏名：堀田 勝幸

所属/身分
金額（年間）

岡山大学病院 呼吸器内科 助教
該当なし 該当有りの場合：企業名等―■

企業等の顧問職100万円以上■

株式・エクイティ

100万円以上の利益、全株式の5％以上

■

講演料など

50万円以上■

原稿料など50万円以上■

寄付金200万円以上■

委受託研究(治験等)総額200万円以上■

専門的助言・証言(裁判)100万円以上■

その他

5万円以上の贈答他

■

法人の代表

試験責任者氏名：國頭 英夫

所属/身分
金額（年間）

企業等の顧問職100万円以上■

株式・エクイティ

100万円以上の利益、全株式の5％以上

■

講演料など

50万円以上□原稿料など50万円以上■

寄付金200万円以上■

委受託研究(治験等)総額200万円以上■

専門的助言・証言(裁判)100万円以上■

その他

5万円以上の贈答他■

Second-line therapy yes/no(n=112/25)%

First-line platinum CT
Cisplatin
Carboplatin
Nedaplatin

865
331
501
33

38.3
57.9
3.8

Accessible for response
CRPRSDPDNE

8004272296162
66

0.5
34.0
37.0
20.3
8.2

Maintenance therapy
Primary study population

194/800
144/506

24.3
28.5

MaintenancetherapyNo. ofpatients%(n=137)

None

79

25.3

25

18.2

2nd-line CT

233

74.7

112

81.8

Docetaxel

101

32.4

42

30.7

Pemetrexed

39

12.5

23

16.8

Erlotinib

15

4.8

12

8.8

TS-1

12

3.9

3

2.2

Gemcitabine

6

1.9

8

5.8

Other

60

19.2

24

17.5

628/23773/24

65 (24-86)
250

29602
174
73
16

70
208
2

343/449/65/7/1

40/52/7/1/0

173/687/5

20/79/1

654/21176/2487/515/263

10/60/30

1142812

1.3
4.9
93.9

No. of patients(n=144)
54
51
13
97
42
1
12%
38.0
35.9
9.2
6.3
4.9
2.8
1.4
0.7
0.7
1.4

Table5. Reasons for not receiving
second-line CT after progression(n=104)
Reasons
DeclinedPS
Patient
refusalDeath ofany cause
Loss offollow-up
and others(n)No maintenancetherapyNo. ofpatients%(n=79)

MaintenancetherapyNo. ofpatients%(n=25)

64

49

62.0

15

60.0

23

14

17.7

936.0

76

7.6

1

4.0

1010

12.7

00Table6. Characteristics of patients with or without maintenance therapy

male/female(range)
70 or more
Adeno
Squamous
NSCLC (NOS)
Others0/1/2/3-4

No maintenance therapy
No. of patients(n=362)%277/8576.5/23.5
67 (24-86)
127
35.1
216
59.7
104
28.7
34
9.4
8
2.3
152/185/22/3
42.0/51.1/6.1/0.9

never/ever/unknown
mutant/wild/unknown

63/296/3
23/140/199(n=506)Sex
Age medianPS
Smoking
EGFR status

Maintenance therapy
No. of patients(n=144)%93/51
64.6/35.4
63 (34-78)
26
18.1
12687.574.9
117.6
00
75/62/6/1
52.1/43.1/4.2/0.7

17.4/81.8/0.8
6.4/55.0/38.7

34/110/0
17/100/25

23.6/76.4/0
11.8/69.4/18.8

Table 7. Association between baseline characteristics and administration of secondline CT yes/no(univariate analysis)
Characteristics

日本イーライリリー%

Bevacizumab
Pemetrexed
TS-1
Pemetrexed+Bevacizumab
TS-1+Bevacizumab
Docetaxel
Gemcitabine
Erlotinib
Pemetrexed+Gefitinib
Other

Table4. Summary of second-line CT
patients with confirmed progression
after CR/PR/SD in first-line CTNo maintenancetherapy
No. ofpatients%(n=312)

No. of patients(n=865)

Table3. Summary of Maintenance CT

No. of patients

No. of patients(n=233/129*)%P

Maintenance therapy
OR(95% CI)

No. of patients(n=112/32*)%

POR(95% CI)

Sex

male
female180/9753/32

65.0/35.0
62.4/37.6

0.213

1.12
(0.679-1.849)

70/23
42/9

75.7/24.4
82.4/17.6

0.404

0.652
(0.281-1,521)

Age

≥70
<70

78/49
155/8061.4/38.6
66.0/34.0

0.422

0.822
(0.526-1.284)

17/9
95/23

61.4/38.6
66.0/34.0

0.118

0.457
(0.184-1.134)

PS

01-4

102/50131/7967.1/32.9
62.4/37.6

0.375

1.230
(0.794-1.905)

64/11
48/21

85.3/14.7
69.6/30.4

0.028

2.545
(1.134-5.704)

Smoking

never
ever

40/23
193/106

63.4/36.6
64.5/35.5

0.886

0.955
(0.545-1.673)

32/2
80/30

94.1/5.9
72.7/27.3

0.009

6.000
(1.492-23.84)

Comorbidities none
yes

173/9360/36

65.0/35.0
62.5/37.5

0.710

1.116
(0.689-1.807)

90/24
22/8

72.6/28.4
73.3/26.7

0.622

1.364
(0.552-3.388)

Platinum
regimen

92/41
141/8869.1/30.9
61.6/38.4

0.172

1.400
(0.890-2.202)

42/8
70/24

84.0/16.0
74.5/25.5

0.213

1.800
(0.753-4.283)

該当なし 該当有りの場合：企業名等■No progression(n=7)

No maintenance therapy

三井記念病院 呼吸器内科 科長―法人の代表)

Maintenancetherapy(n=194)Characteristics
Sex
male/female
Age
median (range)
70 or moreHistology
Adeno
Squamous
NSCLC (NOS)
OthersPS
0/1/2/3-4/unknown
Smoking
never/ever/unknown
Comorbidities
none/any
EGFR status
mutant/wild/unknown
ALK-EML translocation
positivenegative
unknown

Table2. Summary of first-line CTHistology
発表者・研究責任者の利益相反開示事項

Maintenancetherapy(n=144)

No progression(n=50)

Acknowledgement

研究費の財源

Table 1. Patient characteristics

CDDP
other

*Patients without progression of first-line CT are included*