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

458s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7026 Poster Discussion Session (Board #18), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
The effect of comorbidity on stage-specific survival in resected non-small
cell lung cancer patients. Presenting Author: MARK Krasnik, Rigshospitalet,
Copenhagen, Denmark
Background: TNM classification has been the traditional cornerstone of
decision-making in treatment choices of lung cancer. In addition to TNM
stage and lung function, there is no other objective information to support
this decision. Severe comorbidity affects overall survival, and may be an
independent prognostic factor. In this study we quantified the effect of
comorbidity on stage-specific survival in resected non-small cell lung
cancer (NSCLC) patients in a large population-based setting. Methods:
Among 3,152 NSCLC patients from the Danish Lung Cancer Registry who
underwent surgical resection between 1 January 2005 and 31 December
2010, mortality hazard ratios were calculated during three consecutive
time periods following surgery (0-1 month, 1 month - 1 year and �1 year)
according to Charlson comorbidity score (CCS 0, 1-2, 3�), ECOG performance
status, lung function, age, sex, pathological T and N stage according
to the revised 7th edition TNM lung cancer staging system, using Cox
proportional hazard modelling. The Kaplan-Meier method was used to
describe stage-specific survival according to the Charlson comorbidity
score. Results: Increasing severity of comorbidity was independently
associated with significantly higher death rates throughout the three
periods of follow-up [HR1.18 for CCS 1-2 and 2.06 for CCS 3� in 0-1
month, 1.13 for CCS 1-2 and 1.57 for CCS 3� during 1 month - 1 year and
1.14 for CCS 1-2 and 1.84 for CCS 3� after 1 year]. Stage-specific
five-year survival in patients with severe comorbidity (CCS 3�) was
significantly lower than in patients without comorbid disease [e.g., 38%
(95% CI 23-53%) for pT1 and CCS 3� vs. 69% (62-75%) for pT1 and CCS
0]. Conclusions: This study shows that severe comorbidity affects survival of
NSCLC patients undergoing surgical resection by as much as a single stage
increment. As the survival of NSCLC patients after different treatment
regiments is mainly based on the TNM classification, further research is
necessary to fully identify which patients are most likely to benefit from
surgery, but also to provide a basis for developing a better prediction
instrument for the survival after combination treatment involving radiotherapy
and chemotherapy.
7028 Poster Discussion Session (Board #20), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Randomized phase III study comparing etoposide and cisplatin (EP) with
irinotecan and cisplatin (IP) following EP plus concurrent accelerated
hyperfractionated thoracic radiotherapy (EP/AHTRT) for the treatment of
limited-stage small-cell lung cancer (LD-SCLC): JCOG0202. Presenting
Author: Kaoru Kubota, National Cancer Center Hospital East, Kashiwa,
Japan
Background: Four cycles of EP plus AHTRT is the standard treatment for
LD-SCLC. IP demonstrated statistically significant overall survival (OS)
improvement compared to EP for extensive-stage SCLC (JCOG9511; Noda,
et al.NEJM, 2002). EP plus AHTRT followed by 3 cycles of IP is feasible
with acceptable toxicities for LD-SCLC (Kubota, et al. CCR,2005). Methods:
Eligibility criteria included patients with previously untreated LD-SCLC
with measurable lesion, ECOG PS of 0-1, age: 20��, ��70 years old.
Eligible patients received one cycle of EP (etoposide 100 mg/m2 on days
1-3 and cisplatin 80mg/m2 on day 1) plus AHTRT (1.5 Gy b.i.d. total 45
Gy/3 weeks). Patients who achieved CR, good PR, PR or SD with induction
EP/AHTRT were randomized to receive either 3 cycles of consolidation EP
or IP (irinotecan 60 mg/m 2 and cisplatin 60 mg/m2 on days 1, 8, 15).
Patients with CR or good PR after consolidation chemotherapy received
prophylactic cranial irradiation. The primary endpoint is OS after the
randomization. The planned sample size for randomization is 250 with a
one-sided alpha of 2.5% and at least 70% power to detect a difference
between gruops, 30% in EP versus 42.5% in IP group in 3-year survival.
Results: From Sep 2002 to Sep 2006, 281 patients from 36 institutions
were registered. After the induction EP/AHTRT, 258 patients were randomized
to consolidation EP (n�129) or IP (n�129). Patient demographics
were well balanced between the two groups. At the final analysis, the
superiority of IP in OS was not demonstrated (hazard ratio of IP to EP,
1.085 [95%CI: 0.80-1.46]; one sided p�0.70, stratifield log-rank test).
Grade 3/4 neutropenia (95%/78%), anemia (35%/39%), thrombocytopenia
(21%/5%), neutropenic fever (17%/14%), diarrhea (2%/10%) were
observed in EP and IP groups, respectively. Conclusions: EP plus AHTRT
followed by 3 cycles of IP failed to demonstrate survival advantage over 4
cycles of EP plus AHTRT which still is the standard treatment for LD-SCLC.
EP IP
Median OS 3.2 years 2.8 years
3-year OS 53% 47%
5-year OS 36% 34%
Median PFS 1.1 years 1.0 year
7027 Poster Discussion Session (Board #19), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Randomized phase II trial comparing two schedules of thoracic radiotherapy
(TRT) in limited disease small-cell lung cancer (LD SCLC).
Presenting Author: Bjørn Henning Grønberg, Department of Cancer Research
and Molecular Medicine, Norwegian University of Science and
Technology and The Cancer Clinic, St. Olavs Hospital-Trondheim University
Hospital, Trondheim, Norway
Background: Concurrent chemotherapy and TRT is standard therapy for
SCLC if all lesions can be included in a radiotherapy field (LD). Several
schedules of TRT are used. One study showed that two fractions a day
improved local control and overall survival (OS), but this schedule has not
been compared to a commonly used 3 wks schedule. Methods: Eligible pts
had LD SCLC and PS 0-2. Pleural fluid was accepted if negative cytology.
Pts received 4 cycles of PE (cisplatin 75 mg/m2 IV day 1 and etoposide 100
mg/m2 IV day 1-3 q 3 wks) and were randomly assigned to 3 wks of 3D
conformal TRT [A] 42 Gy (2.8 Gy x 1/day) or [B] 45 Gy (1.5 Gy x 2/day). TRT
started 3-4 wks after the first PE. All responders received prophylactic
cranial irradiation (PCI) 2 Gy x 15 � 6 wks after last PE. Pts reported health
related quality of life (HRQoL) on EORTC QLQ C30 � LC13. Primary
endpoint: 1-year local failure. Secondary: OS, toxicity and HRQoL (dysphagia
and dyspnea; a difference � 10 points was considered significant). 75
pts were required in each arm to show a 30% improvement of local disease
control with ��.05 and ��.8. Results: 159 eligible pts were enrolled at 18
sites in Norway May 05 – Jan 11 (A: 85, B: 74). Median age 60 (40-85);
52% men, 84 % PS 0-1, 11% pleural fluid. Mean no. of PE-cycles was 3.8,
97% completed TRT, 82 % PCI (no difference between arms). Response
rates were similar (A: 92%, B: 94%; p�.8), but more pts on Arm B had CR
(A: 13%, B: 35%; p�.01). There was no difference in local failure as first
site of progression at 1 year (A: 17%, B: 12%; p�.4) or 1-year PFS (A:
44%, B: 50% ; p�.4). There was similar grade 3-4 esofagitis (A: 33%, B:
37 %; p�.7) and pneumonitis (A: 6 %, B: 7 %; p�.9). 2 pts (1 on each
arm) died from pneumonitis. Pts in Arm B reported more dysphagia (A: 64
points, B: 73 points), but not more dyspnea (A: 29 points, B: 28 points).
1-year OS was similar (A: 77%, B: 76%; p�.9). Currently, 2-year survival
among those followed � 2 years (n�130) favors Arm B (A: 40%, B: 55%;
p�.09) and so far (all pts followed � 1-year; 103 events) median OS favors
Arm B (A: 18.7 mos, B: 26.6 mos; p�.34). Conclusions: Twice daily TRT
resulted in more CRs, slightly more dysphagia, similar 1-year local control
and 1-year PFS. There are indications of improved 2-year and median OS in
this arm.
7029 Poster Discussion Session (Board #21), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Randomized phase II trial of pemetrexed/cisplatin with or without CBP501
in patients with advanced malignant pleural mesothelioma (MPM). Presenting
Author: Lee M. Krug, Memorial Sloan-Kettering Cancer Center, New
York, NY
Background: CBP501, a synthetic duodecapeptide, enhances the cytotoxicity
of cisplatin in cell lines and xenografts, including NCI-H226 human
mesothelioma. CBP501 increases cisplatin influx into tumor cells through
an interaction with calmodulin, and inhibits cell cycle progression by
abrogating DNA repair at the G2 checkpoint. Phase I clinical trials
combining CBP501 with cisplatin alone or with pemetrexed showed
acceptable safety profiles and suggested activity. The most common
toxicity of CBP501 is infusion-related urticaria, which is easily managed
with diphenhydramine. Methods: Chemotherapy-naive patients with unresectable
MPM were stratified by histology (epithelioid vs other) and
performance status (PS 0-1 vs 2) and randomized 2:1 to Arm A:
pemetrexed/cisplatin plus CBP501 25 mg/m2 IV (42 pts planned), or Arm
B: pemetrexed/cisplatin alone at standard doses (21 pts planned). Patients
continued on treatment until progression or intolerance; no maintenance
therapy was delivered. The primary endpoint is progression free survival
(PFS) in Arm A; if � 23 of the 42 patients remain free of progression more
than 4 months, the combination will be deemed worthy of further study. In
addition to standard CT imaging to assess response and PFS, PET scans,
pulmonary function tests, and mesothelin levels were performed. Results:
Enrollment was completed in October 2011. 65 pts from 14 institutions
were randomized, and 63 were treated. Patient characteristics in the two
arms were similar and as follows: median age 65, 82% male, 71%
epithelioid histology, 8% PS2. Grade 3/4 treatment-related toxicities were
uncommon, no different than expected from standard chemotherapy, and
comparable in the two arms. 70% of patients treated with CBP501 had
infusion reactions, all grade 1-2. The best overall response rate in evaluable
patients (modified RECIST, investigator assessed) was 12/37 (32%) (95%
CI 18-50) in Arm A, and 3/22 (14%) (95% CI 3-35) in Arm B. The median
number of chemotherapy cycles was 5.5 in Arm A, 5 in Arm B. Conclusions:
Data on the primary endpoint of PFS in Arm A are maturing and will be
presented at the meeting.
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