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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7088 General Poster Session (Board #40G), Sat, 1:15 PM-5:15 PM
Efficacy of rechallenge chemotherapy in patients with sensitive relapsed
small cell lung cancer. Presenting Author: Kazushige Wakuda, Division of
Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
Background: Treatment efficacy of rechallenge chemotherapy recommended
for patients with sensitive-relapse small cell lung cancer (SCLC)
has not been fully clarified. Methods: We defined sensitive relapse as
treatment-free interval (TFI) � 90 days. Sixty-five sensitive-relapse SCLC
patients who received second-line chemotherapy at the Shizuoka Cancer
Center between September 2002 and May 2011 were separated into those
treated with rechallenge chemotherapy (rechallenge group) and those
treated with other regimens (other group) for comparison and analysis of
treatment efficacy. Results: No significant differences in age, gender, ECOG
performance status at relapse, disease extent at diagnosis, or response to
first-line treatment were found between the two groups, but TFI was
significantly longer in the rechallenge group, which included 19 sensitiverelapse
patients. The other group included 46 sensitive-relapse patients,
21 of whom received amrubicin. There was no significant difference in
overall survival (OS) between the two groups (median survival time (MST):
rechallenge group 14.4 months, other group 13.1 months, p � 0.51). In
the patients treated with amrubicin, MST was 12.6 months. Comparing the
rechallenge group with the patients treated with amrubicin, there was also
no significant difference in OS (p � 0.38). Both the rechallenge and other
group included 11 patients with ex-sensitive relapse (TFI � 180 days).
There was no significant difference in OS between the two groups (MST
15.7 vs. 26.9 months, p � 0.46). Conclusions: Rechallenge chemotherapy
did not prove superior to other chemotherapies, suggesting that monotherapy,
such as amrubicin, might be reasonable as second-line chemotherapy
for sensitive-relapse SCLC patients.
7090 General Poster Session (Board #41A), Sat, 1:15 PM-5:15 PM
Phase II trial of huKS-IL2 with cyclophosphamide (CTX) in patients with
extensive disease small-cell lung cancer (ED-SCLC). Presenting Author:
Oleg Gladkov, Chelyabinsk Regional Clinical Oncology Dispensary, Chelyabinsk,
Russia
Background: huKS-IL2 immunocytokine is a humanized antibody specific
for EpCAM, fused at its Fc end to two molecules of IL2. Results of a phase
1b study of huKS-IL2 plus low-dose CTX, and preclinical data, provided a
rationale to evaluate this combination in SCLC, which is often EpCAMpositive.
Methods: Patients (pts) with ED-SCLC responding (PR/CR) to 4
cycles of first-line Pt-based chemotherapy were randomized 1,5:1 to
receive huKS-IL2/CTX or best supportive care (BSC). Pts in the huKS-IL2/
CTX arm received six 21-day cycles of CTX 300 mg/m2 on day (d) 1, and 1.5
mg/m2 /d huKS-IL2 on d2–4, followed by 21-d cycles of CTX on d1 and
huKS-IL2 on d2 until progression. Pts were stratified for prophylactic
cranial irradiation (PCI) and response to chemotherapy. Primary endpoint
was PFS rate at 6 months (mo). Secondary endpoints included OS rates at
12 and 18 mo from start of Pt-based chemotherapy, median PFS and OS,
safety, and immunogenicity. Results: 108 pts (64 huKS-IL2/CTX arm, 44
BSC arm) were randomized and treated. Baseline characteristics were
balanced between arms; however, higher % of males (75 vs 61.4%) and of
ECOG PS 0 (45.3 vs 38.6%) were observed in the active arm. Median age
was 61.7 (32; 81) and 59.2 (45; 74) years in the active and BSC arm,
respectively. Most pts were in PR at randomization (2 pts–1ineach arm –
had CR). PCI was used in 15 (23.4%) and 11 (25%) pts in the active and
BSC arm, respectively. No significant differences in PFS or OS were
observed in the active vs BSC arm: PFS rate was 6.4 vs 12.2%; median PFS
was 1.5 vs 1.4 mo; OS rates at 12 and 18 mo were 52 vs 61% and 24 vs
29%, respectively; median OS was 12.3 vs 14.1 mo. One PR (45%
reduction vs randomization baseline) was observed in the active arm. In a
subset of pts who received PCI, median PFS was 1.7 vs 1.5 mo, median OS
21.5 vs 14.3 mo in the active vs BSC arm, respectively. AEs observed more
frequently in the active arm were flu-like symptoms, rash, hypotension,
lymphopenia, LFT and creatinine elevations; all Grade 3/4 AEs related to
huKS-IL2 were reversible/manageable. Conclusions: HuKS-IL2/CTX was
well tolerated, but showed no benefit in pts with ED-SCLC in PR/CR after
chemotherapy. A trend for improved PFS and OS was observed in pts who
received prior PCI.
473s
7089 General Poster Session (Board #40H), Sat, 1:15 PM-5:15 PM
Genome-wide association study of survival in small cell lung cancer
patients treated with irinotecan and cisplatin chemotherapy. Presenting
Author: Ji-Youn Han, Center for Lung Cancer, National Cancer Center,
Goyang, South Korea
Background: The prognosis of patients with extensive-disease small-cell
lung cancer (ED-SCLC) remains poor. Despite a high initial response rate to
chemotherapy, most patients die from rapid recurrence. We conducted a
genome-wide analysis study (GWAS) to examine whether germline genetic
variations are prognostic factors in ED-SCLC patients treated with irinotecan
and cisplatin (IP) chemotherapy. Methods: We prospectively collected
blood samples from 139 patients who participated in two phase II studies
of IP chemotherapy as first-line therapy and conducted a GWAS using
overall survival (OS) as the endpoint. Germline DNA was genotyped using
the Affymetrix 5.0 or 6.0 array sets. Associations between OS and single
nucleotide polymorphisms (SNPs) were investigated using multivariate Cox
regression analysis. Adjustments for age, performance status (PS) and
gender were made. We selected most promising SNPs with p�1�10�6 in
the GWAS allelic association analyses. Results: A total of 426,019 SNPs
were genotyped and 343,530 SNPs passed quality control (HWE, p�10-7 ,
minor allele frequency�1%). We found 7 SNPs showing a significant
association with OS. Patients harboring rs16950650 CT, rs7186128 AG
or GG, rs17574269 AG, rs8020368 CC, rs4655567 CC, rs2166219 TT
and rs2018683 TT genotypes showed shorter OS compared to patients
with control alleles. Hazards ratios of death for each risk variants were 30.2
(95% CI, 8.3-109.0, p�2.1X10-7 ), 2.5 (95% CI, 1.7-3.5, p�3.8X10-7 ),
7.6 (95% CI, 3.4-16.6, p�4.5X10-7 ), 3.4 (95% CI, 2.1-5.5, p�3.5X10-7 ),
4.9 (95% CI, 2.7-9.0, p�3.1X10-7 ), 5.8 (95% CI, 2.9-11.7, p�8.4X10-7 )
and 7.8 (95% CI, 3.4-17.7, p�8.0X10-7 ), respectively. Among these
SNPs, rs4655567, rs8020368, rs2018683 and rs17574269 were significantly
associated with a refractory relapse. In multivariate logistic analysis
including age, gender and PS, rs8020368 CC genotype showed higher risk
of refractory relapse than patients with TT or TC genotype (HR�14.9 [95%
CI, 1.9-114.8], p�0.010). Conclusions: This exploratory GWAS identified
several candidate SNPs that might predictive for the outcome of patients
with ED-SCLC receiving IP chemotherapy.
7091 General Poster Session (Board #41B), Sat, 1:15 PM-5:15 PM
Randomized phase II study of recombinant human endostatin in combination
with chemotherapy in previously untreated extensive-stage small-cell
lung cancer (NCT00912392). Presenting Author: Shun Lu, Shanghai Lung
Cancer Center, Shanghai Chest Hospital, Shanghai, China
Background: Endostar (recombinant human endostatin) is a novel antiangiogenesis
drug developed in China for non-small cell lung cancer (NSCLC).
Because of promising efficacy signals, we performed a randomized phase II
trial to assess the efficacy and safety of adding endostar to first-line
standard chemotherapy for treatment of chemonaive extensive-stage smallcell
lung cancer (SCLC). Methods: Extensive-stage SCLC patients with a
performance status 0-2 were randomly assigned to endostar group (endostar
7.5mg/m2 D1-D14 with carboplatin AUC�5 plus etoposide 60mg/m2 D1-D5 of a 21-day cycle for six cycles) or the control group (the same dose
of carboplatin plus etoposide). Patients in endostar treatment group with
CR, PR and SD were treated with single-agent endostar until progression or
unacceptable toxicity. The primary end point is progression-free survival
(PFS). The secondary end points are overall survival (OS) and response rate
(RR). Results: 140 patients were enrolled from June 2009 to June 2011,
and 137 patients were included in full analysis set. 68 patients were
randomly assigned to the endostar treatment and 69 patients to the control
group. Median age was 57 years and 80.9% for male in the endostar group
while median age was 58 years and 85.5% for male in the control group.
Median PFS was similar for endostar and control group (6.2 v 5.9 months,
P�0.163, HR 0.762; 95%CI 0.519-1.119). Median overall survival (OS)
was also similar for both groups (12.4 v 12.3 months, P�0.475, HR
0.835; 95%CI 0.508-1.371). Overall RR were 76.5% for endostar group
and 68.1% for the control group (p�0.275). 20 patients in the endostar
group completed six cycles of therapy and subsequently treated with
single-agent endostar as maintenance therapy and the median PFS and OS
were 6.8 and 12.4 months respectively. The rate of � 3 grade adverse
events occurred in both groups was similar and no new or unexpected safety
signals for endostar were observed. Conclusions: The addition of endostar to
carboplatin plus etoposide for treatment of extensive stage SCLC didn’t
improve the PFS significantly, with an acceptable toxicity profile. And no
improvement in OS was observed.
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