ESMO 2012#1306P

Initial report of cohort study in patients with non-small-cell lung cancer (NSCLC)
who were treated with 1st-line platinum-based chemotherapy (SAPPHIREstudy)
Y. Naito1,7, K. Kishi2,7, K. Yoh3, Y. Goto4, Y. Ohashi5, H. Kunitoh6
1. Department of Hematology and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan; 2. Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital; 3. Thoracic Oncology Division, National Cancer Center Hospital East;
4. Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo; 5. Department of Biostatistics, School of Public Health, University of Tokyo; 6. Department of Respiratory Medicine, Mitsui Memorial Hospital; 7. Department of Medical Oncology, Toranomon Hospital【Result】【Abstract】
Background
Although 2nd-line chemotherapy comprises the standard of care for NSCLC, not every patient could
receive one. How many and why did they miss the opportunity are not fully investigated.
Methods
We prospectively registered consecutive patients with NSCLC treated with platinum-based 1st-line
therapy from April 2010 to September 2011 from 30 institutions in Japan. Baseline characteristics,regimens and responses for the 1st-line therapy, whether the patients received 2nd-line chemotherapy
or not, and if not treated, the reason was recorded. This study was supported by the Public HealthResearch Center Foundation CSPOR.
Results
A total of 866 patients were registered. Patient characteristics were: median age, 65 (24 - 80); female
patients, 27.5%; ECOG PS 0 or 1, 91.6%; adenocarcinoma, 69.6%; squamous cell carcinoma, 20.1%;
never smoker, 20.1%; EGFR activating mutation positive, 10.2%. Maintenance chemotherapy wasadministered to 28.9% (131 / 454) of patients whose disease did not progress during the course of 1stline chemotherapy. Among 592 patients with at least 6 months of follow-up, 193 were excluded (129 PD
during the course of 1st-line chemotherapy, 20 ongoing 1st-line chemotherapy, and 44 others). The
remaining 399 patients were analyzed with regard to administration of 2nd-line chemotherapy. A total of
135 patients (33.8%) did not receive 2nd-line chemotherapy, and the reasons were: without diseaseprogression, 42 (31.1%); declined PS, 55 (40.7%); patient refusal, 20 (14.8%); death of any cause, 5(3.7%). Therefore, approximately 20% of patients missed their opportunity to receive appropriate 2ndline chemotherapy during follow-up period after completion of effective 1st-line therapy.
Conclusions
This is the largest prospective observational study exploring the proportion and the reasons for NSCLC
patients not receiving 2nd-line chemotherapies. Further investigations to identify predictive factors for‘missing the opportunity for 2nd-line chemotherapy’ are underway.

【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 patients withNSCLC4-7.
・Subgroup of patients who are benefited by maintenance chemotherapy is still to be determined.
・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-line chemotherapy.

【Methods】

・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 offactors which hinders patients from receiving 2nd-line chemotherapy

Patient characteristics
Age (median, years) (range)

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 inJapan
・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 mass index,
histological subtype, EGFR mutation, ALK translocation, CBC/chemistry at registration
・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)・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%); patient refusal, 28(15.6%); death of any cause, 6 (3.4%).

Factor%65 (24 – 86)

2nd line therapy (N=479)
Number of patients (%)

No (n=125)

Yes (n=354)

male98 (78.4)

254 (71.8)

female27 (21.6)

100 (28.2)<65

43 (34.4)

168 (47.5)≧65

82 (65.6)

186 (52.5)

Univariate
P value*p = 0.1587

Gender male/female

628/238

72.5/27.5

PS (ECOG) 0/1/2/3-4

343/450/65/7

39.6/52.0/7.5/0.8

654/21275.5/24.5

ageadenocarcinoma

603

69.6

PS

174

20.1

31 (24.8)
94 (75.2)

170 (48.0)
184 (52.0)<0.0001squamous cell carcinoma

01-4

large cell carcinoma

91.0

Smokingnever

15 (12.0)

76 (21.5)

0.0237other80

9.2

exp/current

110 (88.0)

278 (78.5)

EGFR mutation (＋)

88

10.2

Comorbidity※ none

84 (67.2)

271 (76.6)

exon21 L858R/exon19 del

42/36

4.8/4.2any

41 (32.8)

83 (23.4)

EGFR mutation (－)

514

59.4

<2046 (36.8)

87 (24.6)

11/42/813

1.3/4.8/93.9≧2079 (63.2)

267 (75.4)

mutation (＋)

5 (3.9)30 (8.2)

never/experienced/current

174/435/252

20.1/50.2/29.1

mutation (－)

79 (61.2)

219 (59.5)

Body mass index (median) (range)

22.1 (13-39.6)

Comorbidities none/anyHistology

ALK translocation (＋)/(－)/unknownSmoking history

1st line Treatment delivery

Number of patients(N=866)

%

332

38.3

152/1017.6/1.2

51

5.9

21
47/20

2.4
5.4/2.3

CDDP+S-1

50.6

CBDCA-based

501

57.9

125/2814.4/3.230

3.5

173/8920.0/10.3

CBDCA+S-1

34

3.9

BV containing regimen

168

19.4

CDDP-based
CDDP+PEM/CDDP+PEM+BV
CDDP+GEM
CDDP+VNR
CDDP+DOC/CDDP+DOC+BV

CBDCA+PEM/CBDCA+PEM+BV
CBDCA+GEM
CBDCA+PTX/CBDCA+PTX+BV

Study Design
・Cohort study【Result (cont.)】

BMI
EGFR

0.01200.04400.0106
0.2598*Fisher’s test, ※DM, cardiac disease, ILD

Factor

Odds ratio

95% CI

Multivariate
P value**Age (≧65 vs <65)0.648

0.416 – 1.011

0.0558PS (1-4 vs 0)

0.395

0.247 – 0.631

0.0001

Smoking (ex/current vs never)

0.500

0.270 – 0.923

0.0268Comorbidities (any vs no)0.649

0.405 – 1.040

0.0722

BMI (≧20 vs <20)

1.565

0.989 – 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 foromitting 2nd-line chemotherapies.
・Maintenance therapy (either switch or continuation) was administered in approximately 30% ofpatients.
・Although data were immature, approximately 30% of patients did not receive appropriate 2nd-linechemotherapy.
・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 significantly correlated.
・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.

Number of patients

%

788

100

CR/PR/SD/PD/NE

4/266/295/161/62

0.5/33.8/37.4/20.4/7.9

Maintenance therapy

620

100

none
PEM/PEM+BV

429
62/21

69.2
10.0/3.4

BV

67

10.8

Erlotinib

30.5

13/11

2.1/1.8

Other

121.9

2nd-line chemotherapy

547

100

none

179

32.7

DOC

149

27.2

PEM

69

12.6

27/16

4.9/2.9

・This study was funded by Comprehensive Support Project for Oncology Research (CSPOR) of Public Health Research Foundation.
・The research institutes are Mitsui Memorial Hospital, Toranomon Hospital, University of Tokyo ,and National Cancer Center Hospital East.
・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, SaitamaCancer 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

S-1183.3【Any question?】other8916.3

Response to 1st line chemotherapy

S-1/S-1+BV

Erlotinib/Gefitinib【References】
1)
2)
3)
4)
5)
6)
7)

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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Non-Small Cell Lung Cancer. version 3.2012. available from http://www.nccn.org/Paz-Ares LG, et al. J Clin Oncol. 2011;29(Suppl 18):Abstract CRA7510.
Pérol M, et al. J Clin Oncol. 2012 Sep 4. [Epub ahead of print].
Cappuzzo F, et al. Lancet Oncol. 2010;11:521-9.
Ciuleanu T, et al. Lancet. 2009;374:1432-40.

【Acknowledgement】

Yoichi Naito, MD Email: ynaito@east.ncc.go.jp
Department of Hematology and Medical Oncology, National Cancer Center Hospital East, Japan