Annual Meeting Proceedings Part 1 - American Society of Clinical ...

452s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7000 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial
for locally advanced non-small cell lung cancer? A pooled analysis of
the literature. Presenting Author: Satomi Yamamoto, National Hospital
Organization Kinki-Chuo Chest Medical Center, Sakai, Japan
Background: There is a growing interest on the efficacy of maintenance
chemotherapy to metastatic non-small cell lung cancer (NSCLC) and
adjuvant chemotherapy to early stage NSCLC. However, the role of
consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy in
locally advanced NSCLC is undetermined. Methods: We systematically
searched PubMed for phase II/III trials examining survival of locallyadvanced
NSCLC treated with concurrent chemo-radiotherapy between
January 1, 1995 and October 31, 2011. Median overall survival (mOS) and
corresponding 95% confidence interval (CI) were collected from each study
and pooled. We extracted log-transformated hazards and its standard errors
under the assumption that survival follows an exponential distribution, and
computed a pooled mOS and its 95% CI using random-effect model.
Collected trial arms were divided into two groups by the presence of CCT:
Arm with CCT (CCT�) and without CCT (CCT-). Results: Forty-five studies
were identified including 9 phase III studies and 36 phase II studies with
51 arms (CCT�: 29, CCT-: 22). Clinical data were comparable in clinical
stage, performance status, cancer histology, gender, and median age
between the two groups. I2 values for assessing heterogeneity were 15.3,
9.1 and 24.2% in overall, CCT� and CCT- studies, respectively. There was
no statistical difference in pooled mOS between CCT� (18.5 month,
95%CI: 16.7-20.5) vs CCT- (18.1 month, 95%CI: 16.5-20.2). In regard to
the � grade 3 toxicities in pneumonitis, esophagitis, and neutropenia,
there was no difference between the two groups throughout the whole
treatment courses. In random effect models, predicted hazard ratio of
CCT� to CCT- was 0.98 (95%CI: 0.8-1.13, p�0.7574). These models
estimated that addition of CCT could not yield more than 3 months of
survival prolongation for patients with locally advanced NCSLC. Conclusions:
The pooled analysis on publication basis failed to provide evidence that
consolidation chemotherapy yields significant survival benefit for locally
advanced NSCLC.
7002 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
Phase II study of pemetrexed (P) plus carboplatin (Cb) or cisplatin (C) with
concurrent radiation therapy followed by pemetrexed consolidation in
patients (pts) with favorable-prognosis inoperable stage IIIA/B non-small
cell lung cancer (NSCLC). Presenting Author: Hak Choy, University of Texas
Southwestern Medical Center, Dallas, TX
Background: There is no consensus chemotherapy regimen with concurrent
radiation therapy (CRT) for inoperable stage IIIA/B NSCLC. P synergizes
with ionizing radiation, as well as with Cb and C in preclinical models.
These doublets have shown efficacy and favorable toxicity profiles in phase
II/III trials. Methods: In this open-label randomized phase II trial, 98pts
with inoperable stage IIIA/B NSCLC (all histologies) were randomized (1:1)
to P 500 mg/m2 plus Cb AUC 5 (PCb) or P 500 mg/m2 plus C 75 mg/m2 (PC) intravenously (IV) every 21 days for 3 cycles. All pts received CRT
64–68 Gy (2 Gy/day, 5 days/week, Days 1–45). Consolidation P 500
mg/m2 IV every 21 days for 3 cycles began 3 weeks after completion of
CRT. The primary endpoint was 2-year overall survival (OS); secondary
endpoints included median OS, time to progression (TTP), overall response
rate (ORR), and toxicity. Results: Since Jun 2007, 98 pts were enrolled
(PCb: 46; PC: 52).Pts were followed until Oct 2011. Mean dose compliance
was PCb: 95.7% P, 97.1% Cb; PC: 89.7% P, 89.1% C. Mean dose
compliance for CRT was PCb: 95.7%; PC: 88.1%. CRT dose interruptions
occurred in PCb: 32.6% and PC: 40.4%. Two-year OS was PCb: 45.2%
(95% confidence interval [CI], 29.3-59.8); PC: 57.6% (95% CI, 41.6-
70.7); p�0.270. Median OS (months) was PCb: 18.7 (95% CI, 12.9-not
assessable [N/A]); PC: 27.0 (95% CI, 23.2-N/A). Median TTP (months)
was PCb: 8.8 (95% CI, 6.0-10.7); PC: 13.1 (95% CI, 8.3-N/A); p�0.057.
The ORR rates were PCb: 52.2% (complete response [CR], 6.5%; partial
response [PR], 45.7%); PC: 46.2% (CR, 3.8%; PR, 42.3%). Grade 4
treatment-related toxicities (% PCb/% PC) were: anemia, 0/1.9; neutropenia,
6.5/3.8; thrombocytopenia, 4.3/1.9; and esophagitis, 0/1.9. No
drug-related deaths were reported. Conclusions: While conclusions are
limited by the size of the trial, this study suggests OS and TTP advantages
for the C-containing arm. Both combinations with CRT appear well
tolerated.
7001 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
GILT study: Oral vinorelbine (NVBo) and cisplatin (P) with concomitant radiotherapy
(RT) followed by either consolidation (C) with NVBo plus P plus best
supportive care (BSC) or BSC alone in stage (st) III non-small cell lung cancer
(NSCLC): Final results of a phase (ph) III study. Presenting Author: Rudolf M.
Huber, Medizinische Klinik Innenstadt, München, Germany
Background: Concurrent chemo-radiotherapy (CT-RT) is considered as a standard
in st III NSCLC. Published trials with C after CT-RT show encouraging but
discordant results. This ph III was set up to assess C in st III NSCLC. Methods:
Patients (pts) received NVBo 50 mg/m² D1, D8, D15 � P 20 mg/m² D1-D4 q4w /
2 cycles (cy) � RT (66 Gy / 33 Fr). C for OR�SD pts: NVBo 60-80 mg/m² D1D8
� P 80 mg/m² D1q3w/2cy�BSC (Arm A) or BSC (Arm B). PFS was the
primary endpoint. Results: From 07/05 to 05/09, 279 pts received CT/RT and
201 pts (72%) were randomised to receive CT�BSC or BSC as C. Toxicity (tox)
G3-4 (% pt) CT-RT/ C (Arm A/B): anaemia 3.2/3.5/1.1; thrombopenia 2.5/1.2/
0.6; neutropenia (N) 11.2/11.7/5.7; febrile N 1.4/1.0/0; nausea (G3) 5.0/4.7/
2.9; vomiting (G3) 3.9/3.5/2.0; anorexia 3.6/1.2/3.0; dysphagia 1.8/2.3/1.0;
fatigue 3.3/ 2.3/1.0; pneumonia/ pneumonitis 2.6/0/2.0; CT-RT pain 2.2;
CT-RT oesophagitis 8.6; 3 toxic deaths. Conclusions: In this ph III, NVBo�P�RT
reports a high level of efficacy (OR 60.7%; DCR 86.0%) and low tox. The DCR is
significantly improved in pts who received C with NVBo� P in eval pts
(p�0.0084). Lung tox was not enhanced by using NVBo�P as C. However no
survival advantage for C was achieved.
Randomisation (N�201)
CT-RT
N�242 eval /279
CT�BSC
N� 76 eval /96
BSC
N�89 eval/ 105
p
Male (%) 71.0 71.9 71.4
Median age
(y, range)
60.3 [33.9-75.7] 60.3 [34.1-75.9] 59.5 [40.4-75.1]
SCC/ADC* (%) 53.0 / 36.2 54.2 / 36.5 53.3 / 36.2
St IIIA / IIIB (%) 17.6 / 82.4 20.8/ 79.2 19.0 / 81.0
ORR ITT (%) 95% CI 55.6 [49.5-61.5] 29.2 [20.4-39.4] 24.8 [16.8-34.2] p�0.48
SCC / ADC* (%)
60.5 / 54.5 34.6 / 25.7 23.6 / 28.9
ORR eval (%) 95% CI 60.7 [54.3-66.9] 36.8 [26.0-48.6] 29.2 [20.0-39.8] p�0.30
SCC / ADC* (%)
66.9 / 57.6 42.9 / 33.3 28.3 / 31.4
DCR ITT (%) 78.5 66.7 56.2 p�0.12
DCR eval (%) 86.0 84.2 66.3 P�0.0084
Median time
Registration-Rando (m)
3.0 2.9
Median PFS ** (m) 6.4 [5-8.7] 5.5 [3.8-7.4] p�0.63
Median OS ** (m) 20.8 [13.5-25.3] 18.5 [13.6-24.7] p�0.87
4 year survival ** (%) 25.3 21.4
* SCC: Squamous; ADC: Adenocarcinoma. ** Calculated from the time of randomisation, after CT-RT, on ITT.
7003 Oral Abstract Session, Mon, 8:00 AM-11:00 AM
A phase III study comparing amrubicin and cisplatin (AP) with irinotecan
and cisplatin (IP) for the treatment of extended-stage small cell lung cancer
(ED-SCLC): JCOG0509. Presenting Author: Yoshikazu Kotani, Department
of Respiratory Medicine, Kobe University Hospital, Kobe, Japan
Background: IP is the standard treatment for ED-SCLC, however often cause
severe diarrhea. AP have shown promising activity in SCLC with fewer
diarrhea. We conducted a phase III trial comparing AP with IP. Methods:
Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-
SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive
either IP or AP, balancing for site, sex, and PS. IP comprised administration
of I (60 mg/m2 ) iv on days 1, 8, and 15, and P (60 mg/m2 ) iv on day1,every
4 weeks. AP comprised administration of A (40 mg/m2 ) iv on day 1-3, and P
(60 mg/m2 ) iv on day1, every 3 weeks. The planned sample size was 141
pts in each arm with a one-sided alpha of 5% and power of 70% and a
non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint
was overall survival (OS). The secondary endpoints were response rate (RR),
progression-free survival (PFS), adverse events (AEs), and quality of life
(QOL). We evaluated pts’ QOL twice: at the baseline and after completion of
the second course. Results: 284 pts were randomized to IP (n�142) and AP
(n�142). Median age was 63, 84% were male, and 56% had PS 0. When
191pts enrolled, more febrile neutropenia (FN) was observed in AP than
anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35
mg/m2 . At the second interim analysis conducted after the completion of
patient accrual, the median OS of AP (15.0 m) was much worse than that of
IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the
non-inferiority margin, so the Data and Safety Monitoring Committee
recommended early publication of the results. Median PFS was 5.7 (IP) vs.
5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs.
77.9% (AP) (p�0.14). AEs in IP and AP arm were Grade 4 neutropenia
(22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea
(7.1% vs.1.4%). Proportion of improvement in physical status of QOL was
37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P�0.227).
Conclusions: AP showed more bone marrow suppression than expected
although it caused less diarrhea. The non-inferiority of AP to IP was not
demonstrated and IP remains the standard treatment for ED-SCLC.
Visit abstract.asco.org and search by abstract for the full list of abstract authors and their disclosure information.