P2-068

Interim results of a multicenter observational study of clinicalprofiles among patients with non small cell lung cancer treatedwith first line platinum based chemotherapy (SAPPHIRE study)
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Y. Hosomi , Y. Naito , Y. Goto , K. Yoh , K. Kishi , Y. Ohashi , H. Kunitoh
1, Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan; 2, Department ofHematology and Medical Oncology, National Cancer Center Hospital East; 3, Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo; 4, Thoracic
Oncology Division, National Cancer Center Hospital East ; 5, Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital; 6, Department of Biostatistics,
School of Public Health, University of Tokyo; 7, Department of Respiratory Medicine, Mitsui Memorial Hospital【Abstract】【Result ①】

Background・Data cutoff at April 2012; updated from abstract submission
・Data of 866 patients were assessable for patient characteristics and details of 1st line
treatment; 788 for response; 620 for maintenance chemotherapy; 547 for 2nd line
chemotherapy; 479 for analysis of factors which hinders patients from receiving 2nd-line
chemotherapy

Although second-line chemotherapy comprises the standard of care for non small cell lungcancer (NSCLC), not every patient can receive it. How many and why patients miss theopportunity of second-line chemotherapy have not been fully investigated. This prospective,
observational study is aimed at elucidating the clinical features and subsequent courses ofpatients with NSCLC after receiving platinum-based first-line chemotherapy.

Patient characteristics

Methods
Patients with advanced NSCLC undergoing first-line, platinum-based chemotherapy
between April 2010 and September 2011 at 30 institutions in Japan were consecutively
enrolled to the study. IRB approval or waiver was granted from each participating institution.
Baseline characteristics, regimens and responses to first-line therapy, whether or not theyreceived second-line chemotherapy, and if not, reasons for non-administration wererecorded. This report describes from patients with at least six months of follow up. This
study was supported by the Public Health Research Center Foundation CSPOR.

Results
A total of 866 patients were registered. Female, 27.5%; median age, 65 (range: 24 - 80);
91.6% were at ECOG PS 0 or 1; 69.6% had adenocarcinoma, 20.1% had squamous cellcarcinoma; 20.1% had never smoked and 10.2% were positive for the EGFR mutation.
Among the 592 patients who were followed up for at least six months, 193 were excluded
from the analysis of second-line chemotherapy due to disease progression during thecourse of first-line chemotherapy (n = 129), continuation of the first-line chemotherapy (n =20) and other reasons (n = 44). Among the remaining 399 patients, 135 (33.8%) did notreceive second-line chemotherapy because the disease had not progressed (31.1%), PS
had declined (40.7%), patient refusal (14.8%) and all-cause death (3.7%).

Conclusions
Preliminary results of this large observational study suggested that around 20% of patients
missed an opportunity to receive appropriate second-line chemotherapy during follow up
after effective first-line therapy. Further study is needed to validate this finding and design
an action plan to ensure that patients receive second-line therapy where appropriate.

【Background】
・Second-line chemotherapy comprises the standard of care for non-small-cell lung cancer(NSCLC)1-3.
・However, not all patients could receive appropriate 2nd-line chemotherapy.
・Recent studies demonstrated that maintenance chemotherapy prolongs survival in patientswith NSCLC4-7.
・Subgroup of patients who are benefited by maintenance chemotherapy is still to bedetermined.
・The proportion of patients who could not receive 2nd-line chemotherapy and the reason forundertreatment is not fully investigated.

【Objectives】
・To investigate the proportion of patients with NSCLC who received 2nd-line chemotherapy
after platinum-based 1st-line chemotherapy.
・To elucidate the reasons and factors which hinder patients from receiving 2nd-linechemotherapy.

Age (median, years) (range)
Gender male / female
PS (ECOG) 0 / 1 / 2 / 3-4
Comorbidities none / anyHistology
adenocarcinoma
squamous cell carcinoma
large cell carcinoma
other
EGFR mutation (＋)
exon21 L858R / exon19 delEGFR mutation (－)
ALK translocation (＋) / (－) / unknown
Smoking history
never / former / current
Body mass index (median) (range)
1st line Treatment delivery%

65 (24 – 86)
628 / 238
343 / 450 / 65 / 7654 / 212

72.5 / 27.5
39.6 / 52.0 / 7.5 / 0.8
75.5 / 24.5

603
174
980
88
42 / 36514
11 / 42 / 813

69.6
20.1
1.0
9.2
10.2
4.8 / 4.2
59.4
1.3 / 4.8 / 93.9

174 / 435 / 252
22.1 (13-39.6)

20.1 / 50.2 / 29.1

Number of patients (N=866)%332
152 / 1051
2147 / 205501
125 / 2830
173 / 89
34168

38.3
17.6 / 1.25.9
2.4
5.4 / 2.30.6
57.9
14.4 / 3.2
3.5
20.0 / 10.3
3.9
19.4

Number of patients%

7884 / 266 / 295 / 161 / 62620429
62 / 2167313 / 1112547179
149
6927 / 161889

100
0.5 / 33.8 / 37.4 / 20.4 / 7.9
100
69.2
10.0 / 3.4
10.8
0.5
2.1 / 1.8
1.9
100
32.7
27.2
12.6
4.9 / 2.9
3.3
16.3

CDDP-based
CDDP+PEM / CDDP+PEM+BV
CDDP+GEM
CDDP+VNR
CDDP+DOC / CDDP+DOC+BV
CDDP+S-1
CBDCA-based
CBDCA+PEM / CBDCA+PEM+BV
CBDCA+GEM
CBDCA+PTX / CBDCA+PTX+BV
CBDCA+S-1
BV containing regimen

Response to 1st line chemotherapy
CR / PR / SD / PD / NE
Maintenance therapynone
PEM / PEM+BV
BV
Erlotinib
S-1 / S-1+BV
Other
2nd-line chemotherapy
none
DOC
PEM
Erlotinib / Gefitinib
S-1
other

【Result②】
・179 patients did not receive 2nd-line chemotherapy at the time of data cutoff; the reasons
were as follows: without disease progression, 50 (27.9%); declined PS, 75 (41.9%); patientrefusal, 28 (15.6%); death of any cause, 6 (3.4%).

【Methods】
Study Design
・Cohort study
Primary Endpoint
・Proportion of patients who received 2nd-line chemotherapy after platinum-based 1st-linechemotherapy
Patient Inclusion
・Patients with advanced or recurrent NSCLC・Platinum-based 1st-line chemotherapy between April 2010 and September 2011 from 30
institutions in Japan
・Platinum-naïve
・Without history of other malignancy
Data Collection
・Patient characteristics including age, gender, performance status (ECOG), smoking status,
comorbidities (diabetes mellitus, cardiac disease, interstitial lung disease), body massindex, histological subtype, EGFR mutation, ALK translocation, CBC/chemistry atregistration
・Details of 1st-, 2nd-, 3rd-line, and maintenance chemotherapy; including regimen,response
・Reason for administration or omitting 2nd-line chemotherapy
・Survival

Number of patients (N=866)

Factormale
femaleage
PS
Smoking
Comorbidity※
BMI
EGFR<65≧65
0
1‐4neverformer /currentnone
any<20≧20
mutation (＋)
mutation (－)

FactorAge (≧65 vs <65)
PS (1-4 vs 0)
Smoking (ex/current vs never)Comorbidities (any vs no)
BMI (≧20 vs <20)

2nd line therapy (N=479)
Univariate
Number of patients (%)
P value*
No (n=125)
Yes (n=354)
98 (78.4)
254 (71.8)
p = 0.1587
27 (21.6)
100 (28.2)
43 (34.4)
168 (47.5)
0.012082 (65.6)
186 (52.5)
31 (24.8)
170 (48.0)<0.0001
94 (75.2)
184 (52.0)
15 (12.0)
76 (21.5)
0.0237110 (88.0)
278 (78.5)
84 (67.2)
271 (76.6)
0.044041 (32.8)
83 (23.4)
46 (36.8)
87 (24.6)
0.010679 (63.2)
267 (75.4)
5 (3.9)30 (8.2)
0.259879 (61.2)
219 (59.5)*Fisher’s test, ※DM, cardiac disease, ILD
Odds ratio
0.648
0.395
0.500
0.649
1.565

95% CI

Multivariate
P value**
0.416 – 1.011
0.05580.247 – 0.631
0.00010.270 – 0.923
0.02680.405 – 1.040
0.07220.989 – 2.477
0.0558**Logistic regression model【Summary and Conclusion】
・This is the largest cohort study exploring the proportion of patients with NSCLC and reasons for omitting 2nd-line chemotherapies.
・Maintenance therapy (either switch or continuation) was administered in approximately 30% of patients.
・Although data were immature, approximately 30% of patients did not receive appropriate 2nd-line chemotherapy.
・Declined PS was the most common reason for hindering 2nd-line chemotherapy.
・Advanced age, declined PS, smoking history, comorbidity, low BMI were correlated with hindrance to 2nd-line therapy in univariate analysis; however EGFR mutation was not significantlycorrelated.
・In multivariate analysis, declined PS and smoking history were associated with hindrance to 2nd-line chemotherapy.
・Further investigation to establish predictive model is currently underway.