1254‐P

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

ComprehensiveSupport
Project

Yasushi Goto1, Kiyotaka Yoh2, Yoichi Naito2, Kazuma Kishi3, Yasuo Ohashi4, Hideo Kunitoh5

UMIN#000006393

1The University of Tokyo, 2National Cancer Center Hospital East, 3Toranomon Hospital,4Chuo University,5Japanese Red Cross Medical Center

Background
Standard care of advanced NSCLC• First‐line platinum‐based chemotherapy (first‐line CT)• Second‐line chemotherapy (second‐line CT) after the progressionof 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.

Results

ObjectiveFigure 1

Table 2. Summary of first‐line CT

Advanced NSCLC patientswith first‐line platinum CT(n=865)

No. of patients

Data colleting (n=39)
Data missing (n=910)

Accessible for response(n=817)

PD/NE=205/25
CR/PR/SD=4/272/296(n=587)

Methods

No progression (n=16)
Data missing (n=1)

Primary study population(n=570)Observation(no maintenance therapy)(n=385)second‐line therapy yes/no(n=273/112)

Characteristics

second‐line therapy yes/no(n=152/33)

No. of patients(n=865)

%
73/24

Sex
male/female

628/237
65 (24‐86)250

29

Histology
Adeno
Squamous
NSCLC (NOS)
Others

602
174
73
16

70
20
82

PS
0/1/2/3‐4/unknown

343/449/65/7/1

40/52/7/1/0

Smoking
never/ever/unknown

173/687/5

20/79/1

Comorbidities
none/any

654/21176/24

87/515/263
11/42/812

10/60/30
1.3/4.9/93.9

Table 5. Reasons for not receiving second‐line CT
after progression

%

865
331
501
33
817
4277306
166
3925
204

No maintenance therapy

38.3
57.9
3.8

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

0.5
33.9
37.1
20.3
4.8
3.1
31.6

Maintenance therapy

%
54.5
17.0

No. of patients(n=33)
176%
51.5
18.2

824

7.1
21.4

19

3.0
27.3

All Patient

No. of patients(n=392)%

No. of patients (n=194)%

Sex male/female

300/9276.5/23.5

115/7959.3/40.7

Age median (range)
70 or more
Histology
Adeno
Squamous
NSCLC (NOS)
Others67 (24‐86)
138

35.2

62 (34‐78)
35

18.0

242
108
348

61.7
27.6
8.7
2.1

175
7
120

90.2
3.6
6.2
0

Sex

PS 0/1/2/3‐4

165/201/23/3

42.1/51.3/5.9/0.8

99/87/6/2

51.0/44.8/3.1/1.0

Age

Smoking
never/ever/smoking/unknown

72/111/205/4

18.4/28.3/52.3/1.0

59/42/93/0

30.4/21.6/47.9/0

EGFR status mutant/wild/unknown

25/218/149

6.4/55.6/38.0

35/128/31

18.0/66.0/16.0

Table 4. Summary of second‐line CT patients with confirmed
progression after CR/PR/SD in first‐line CT
No maintenance therapy

Maintenance therapy

No. of patients(n=112)
61
19

Table 6. Association between baseline characteristics and administrationof second‐line CT yes/no(univariate analysis)Table 3. Characteristics of patients with orwithout maintenance therapy
No maintenance therapy

Agemedian (range)
70 or more

ALK‐EML translocation
positive/negative/unknown

First‐line platinum CT
Cisplatin
Carboplatin
Nedaplatin
Accessible for response
CRPRSDPDNE
Other
Maintenance therapy

Maintenance therapy(n=185)

Table 1. Patient characteristics

EGFR status
mutant/wild/unknown

Acknowledgement• Preliminary results of this large observational study in Japan suggested that
• Proportion of patients who did not received second‐CT was 29.1% in patients who did not received maintenance therapy,
and 17.8% who received maintenance therapy. Administration of maintenance therapy did not appear to compromise,rather increased the chance to receive second‐line CT.
• Even after adjusting with risk factors for not receiving second‐line Ct, approximately 20% of patients with no maintenancetherapy missed the opportunity to receive second‐line CT. It seems to be difficult to prognos patient who can receive
second‐line CT.
• Response to first‐line CT was not an associated factor for administration of second‐line CT.

• 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.

• 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.

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 not administered)• Survival
Data cutoff• Interim report describing patients with at least 6 months of follow up atApril 2012
Support• Supported by the Public Health Research Center Foundation CSPOR

Conclusions

Characteristics

No. of patients with
Second‐CT (%)
Yes

Total

No maintenance therapy
No. of patients with
Second‐CT (%)

OR (95% CI)

NoYes

OR (95% CI)

No

Maintenance therapy
No. of patients with
Second‐CT (%)
Yes

OR (95% CI)

No425

145

273

112

152

33

male

296 (72.5)

112 (27.5)

0.68 (0.43‐1.07)

205 (69.7)

89 (30.3)

0.78 (0.44‐1.37)

91 (79.8)

23 (20.2)

female129 (79.6)

33 (20.4)

p=0.0968 (74.7)

23 (25.3)

p=0.4361 (85.9)

10 (14.1)

p=0.33<70

310 (77.1)

92 (22.9)

1.55 (1.02‐2.36)

183 (73.2)

67 (26.8)

1.37 (0.85‐2.21)

127 (83.6)

25 (16.4)

1.63 (0.60‐4.34)≥70

115 (68.5)

53 (31.5)

p=0.0489 (66.4)

45 (33.6)

p=0.2025 (75.8)8 (24.2)

p=0.310207 (80.9)

49 (19.1)

1.86 (1.23‐2.81)

126 (77.8)

36 (22.2)

1.82 (1.19‐2.97)

81 (86.2)

13 (13.8)

1.76 (0.77‐4.06)

1‐4

218 (69.4)

96 (30.6)

p=0.002146 (65.8)

76 (34.2)

p=0.0171 (78.0)

20 (22.0)

p=0.182.430 (0.82‐7.68)

0.65 (0.2‐1.55)

PS
never

102 (83.6)

20 (16.4)

1.98 (1.17‐3.33)

56 (78.9)

15 (21.1)

1.67 (0.90‐3.10)

46 (90.2)

5 (9.8)ever

323 (72.1)

125 (27.9)

p=0.01217 (69.1)

97 (30.9)

P=0.11106 (79.1)

28 (20.9)

p=0.091.55 (0.57‐4.12)

Smoking

Maintenance therapynone

336 (77.1)

100 (22.9)

1.70 (1.09‐2.65)

210 (73.7)

75 (26.3)

1.64 (0.99‐2.74)

126 (83.4)

25 (16.6)

yes

89 (66.4)

45 (33.6)

p=0.0263 (63.0)

37 (37.0)

p=0.0626 (76.5)

8 (23.5)

p=0.33

Platinum
regimenCDDP

170 (80.6)

41 (19.4)

1.69 (1.10‐2.60)

116 (78.4)

32 (21.6)

1.85 (1.12‐3.06)

54 (85.7)

9 (14.3)

1.47 (0.60‐3.69)

255 (71.0)

104 (29.0)

p=0.01157 (66.2)

80 (33.8)

p=0.0198 (80.3)

24 (19.7)

p=0.42

1st line
response

CR/PR

206 (75.7)

66 (24.3)

1.69 (0.76‐1.68)

112 (71.8)

44 (28.2)

0.92 (0.56‐1.49)

94 (81.0)

22 (19.0)

0.81 (0.34‐1.91)SD

219 (73.5)

79 (26.5)

p=0.56161 (70.3)

68 (29.7)

p=0.7358 (84.1)

11 (15.9)

p=0.69Yes

152 (82.2)

33 (17.8)

1.89 (1.20‐2.99)

No

273 (70.9)

112 (29.1)

p=0.004

Comorbidities

No. of patients(n=385)%

No. of patients(n=185)%None
2nd‐line CT

112
273

29.1
70.9

33152

17.8
82.2

Docetaxel

112

29.1

5429.2Pemetrexed

4411.42714.6Erlotinib

225.7

1910.3TS‐1

143.673.8

Other

74

19.2

3418.4

Other

MaintenanceThis 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, NTT Medical Center Tokyo, Teikyo University School of Medicine, National Center for Global Health and Medicine

Presented at the ESMO 2014,Contact: ygoto‐tky@umin.net Madrid, Spain, Sep 26‐30, 2014