10‐022 Prospective observational cohort study of second‐line chemotherapy administration after first‐lineplatinum‐based chemotherapy for patients with advanced NSCLC in Japan(SAPPHIRE study)

ComprehensiveSupport
Project

Yasushi Goto1, Kiyotaka Yoh2, Kazuma Kishi3, Yasuo Ohashi1, Hideo Kunitoh4

UMIN#000006393

1The University of Tokyo, 2National Cancer Center Hospital East, 3Toranomon Hospital,4Mitsui Memorial Hospital

BackgroundResults

Conclusions

Standard care of advanced NSCLC• First‐line platinum‐based chemotherapy (first‐line CT)• Second‐line chemotherapy (second‐line CT) after theprogression of the first‐line CT
Maintenance therapy after the first‐line CT• Recently, maintenance therapy has been reported to bebeneficial.
• 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, 797 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 (17.2%) could not receive second‐line CT.
• Observation with no maintenance therapy was done in 362 patients. Of those,• 40 patients did not progress.
• of 322 patients progressed, 89 patients (27.6%) could not receive second‐line CT.
• Decline of PS was the principal reason for not receiving second‐line CT in both patients with and without maintenance CT.

• Preliminary results of this large observational study in Japan suggested that
• Among the patients who did not received maintenance therapy, 27.6% missed an opportunity toreceive appropriate second‐line CT.
• We could not find associated factors for not receiving second‐line CT.
• As for the patients who received maintenance therapy, 17.2% did not receive 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 the patients who would be less likely to receive thesecond‐CT after disease progression, and thus would be more likely to receive benefit frommaintenance therapy strategy.

Objective• 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 second‐line CT
administration in advanced NSCLC patients.

Figure 1
Advanced NSCLC patientswith first‐line platinum CT(n=865)
Data colleting (n=65)
Data missing (n=3)
Accessible for response(n=797)
PD/NE=162/63

Methods
Study design• Cohort (prospective observational) study
Primary endpoint• Proportion of patients who received second‐line CT after first‐line CT
Patient 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, ECOG‐PS, smoking status,
comorbidities, body mass index, histological subtype, EGFR/ALK
status, CBC/chemistry at registration)• Regimens and responses to the first/second/third‐line CT(regimen, response)• Administration of maintenance CT• Reason for not receiving second‐line CT (if it was notadministered)• Survival
Data cutoff• Interim report describing patients with at least 6 months offollow up at April 2012
Support• Supported by the Public Health Research Center Foundation
CSPOR

Acknowledgement

CR/PR/SD=4/272/296(n=572)
No progression (n=51)
Data missing (n=15)

First‐line platinum CT
Cisplatin
Carboplatin
Nedaplatin

No. of patients
865
331
501
33

38.3
57.9
3.8

Accessible for response
CRPRSDPDNE
Maintenance therapy

797
4272
296
162
63
144

0.5
34.1
37.1
20.3
7.9
18.1

Primary study population(n=506)
Observation(no maintenance therapy)(n=362)

Maintenance therapy(n=144)
No progression(n=7)
second‐line therapy yes/no(n=112/25)

Table 1. Patient characteristics
Characteristics
Sex
male/female
Age
median (range)
70 or more
Histology
Adeno
Squamous
NSCLC (NOS)
OthersPS
0/1/2/3‐4/unknown
Smoking
never/ever/unknownComorbidities
none/any
EGFR status
mutant/wild/unknown
ALK‐EML translocation
positive/negative/unknown%

No maintenance therapy
No. of patients(n=322)%

Table 3. Summary of Maintenance CTNo progression(n=40)
second‐line therapy yes/no(n=233/89)

Table 5. Summary of second‐line CT patients withconfirmed progression after CR/PR/SD in first‐line CT

Table 2. Summary of first‐line CT

No. of patients(n=865)%628/23773/24

65 (24‐86)
250

29602
174
73
16

70
20
8
2

343/449/65/7/1

40/52/7/1/0

173/687/520/79/1

654/21187/515/263
11/42/812

76/24

No. of patients(n=144)
54
51
13974
2112

Bevacizumab
Pemetrexed
TS‐1
Pemetrexed+Bevacizumab
TS‐1+Bevacizumab
Docetaxel
Gemcitabine
Erlotinib
Pemetrexed+Gefitinib
Other%
38.0
35.9
9.2
6.3
4.9
2.8
1.4
0.7
0.7
1.4

No maintenance therapy%

Sex male/female

277/85

Age median (range)
70 or more

67 (24‐86)
127

Histology
Adeno
Squamous
NSCLC (NOS)
OthersPS 0/1/2/3‐4

10/60/30

Smoking
never/ever/unknown

1.3/4.9/93.9

EGFR status
mutant/wild/unknown

216
104
348
152/185/22/3
63/296/3
23/140/199

76.5/23.5

93/51

64.6/35.4

35.1

63 (34‐78)
26

17.4/81.8/0.8
6.4/55.0/38.7

27.6
72.4

25
112

18.2
81.8

Docetaxel

101

31.3

42

30.7

Pemetrexed

39

12.1

23

16.8

Erlotinib

15

4.7

128.8

TS‐1

12

3.7

3

2.2

Gemcitabine

6

1.9

8

5.8

Other

60

18.6

24

17.5

Table 6. Reasons for not receiving second‐line CT
after progression
No maintenance therapy
No. of patients(n=89)%
4955.11415.7

Reasons
Declined PSPatient refusal
Death of any cause
Loss of follow‐up and others

620

Maintenance therapy
No. of patients(n=25)
%
15
60.0
936.0

6.7
2.2

10No maintenance therapy%

42.0/51.1/6.1/0.9

89233

4.0
0

Maintenance therapy
No. of patients(n=144)

59.7
28.7
9.4
2.3

None
2nd‐line CT

Table 7. Association between baseline characteristics andadministration of second‐line CT yes/no(univariate analysis)Table 4. Characteristics of patients with orwithout maintenance therapy
No. of patients(n=362)

Maintenance therapy
No. of patients(n=137)%126
711075/62/6/1
34/110/0
17/100/25

18.1
87.5
4.9
7.6
052.1/43.1/4.2/0.7
23.6/76.4/0
11.8/69.4/18.8

This study was funded by Comprehensive Support Project for Oncology 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, University of 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
Graduate School Of Medicine, Okayama University Hospital, Hiroshima Prefectural Hospital, Kurume University School of Medicine, Nagasaki University Hospital, Mitsui Memorial Hospital, University of Tokyo Hospital, National Cancer Center Hospital East, Toranomon Hospital, Nishigunma National Hospital, NTTMedical Center Tokyo, Teikyo University School of Medicine, National Center for Global Health and Medicine

No. ofpatients(n=233/129*)

Maintenance therapy%P
OR (95% CI)

No. ofpatients(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
66.0/34.00.118
0.457(0.184‐1.134)

PS0
1‐4

102/50131/7967.1/32.9
62.4/37.60.375
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)

42/870/24

84.0/16.0
74.5/25.5

1.800(0.753‐4.283)

Characteristics

CDDP
other*Patients without progression of first‐line CT are included*

Presented at the IASLC15th World Conference on Lung Cancer,
Sidney, Australia, Oct 27‐Oct 30, 2013