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

464s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7052 General Poster Session (Board #36C), Sat, 1:15 PM-5:15 PM
5-day dosing schedule of temozolomide in relapsed sensitive or refractory
small cell lung cancer (SCLC) and methyl-guanine-DNA methyltransferase
(MGMT) analysis in a phase II trial. Presenting Author: Alexander Edward
Dela Cruz Drilon, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: MGMT promoter methylation and loss of MGMT activity are
associated with improved sensitivity to alkylating agents. We recently
reported that the oral alkylating agent temozolomide is active in 2nd- and
3rd-line treatment of relapsed SCLC at 75mg/m2 /day for 21 out of 28 days
(Pietanza et al, Clin Can Res 2012). Here we evaluate the 5-day dosing
schedule of temozolomide in a second cohort of patients and analyze
MGMT activity in both cohorts of patients on the same study. Methods:
Patients with disease progression after 1 or 2 prior chemotherapy regimens
received temozolomide at 200mg/m2 /day for 5 out of 28 days (n�25).
Those with sensitive (S-SCLC, n�16) and refractory (R-SCLC, n�9)
disease were enrolled to assess safety. Available tumor tissue from patients
treated according to either schedule was assessed for MGMT promoter
methylation status by PCR and MGMT expression by immunohistochemistry
(IHC). Results: An overall response rate of 12% was noted (3 partial
responses: 1 S-SCLC, 2 R-SCLC). 4 patients had stable disease for at least
3 cycles. Median progression-free survival and overall survival for all
patients were 1.3 months and 7.9 months, respectively. Grade �3
thrombocytopenia and neutropenia was observed in 20% with a shorter
mean duration of myelosuppression compared to the 21-day schedule.
Results from MGMT evaluation of tumor samples from both dosing
schedules were combined. Promoter methylation of MGMT was not
significantly associated with response (p�0.23). However, patients that
lacked MGMT expression by IHC had a higher response rate compared to
those with MGMT-positive tumors (43% vs. 13%, p � 0.052; see table).
Conclusions: The 5-day dosing schedule of temozolomide is both active and
safe in patients with relapsed SCLC. A strong trend toward increased
response was demonstrated in patients with MGMT-negative tumors
compared to patients with MGMT-positive tumors by IHC. A trial combining
temozolomide with the PARP inhibitor, ABT888, is planned.
MGMT expression by IHC (n�38) PR
Response
SD � POD p
Negative (n � 14) 43% (n�6) 57% (n�8) 0.052
Positive (n � 24) 13% (n�3) 88% (n�21)
7054 General Poster Session (Board #36E), Sat, 1:15 PM-5:15 PM
Are the presenting characteristics and prognosis of primary salivary
gland-type lung cancers (SG) similar to those of other non-small cell lung
cancers (NSCLC)? Presenting Author: John M. Varlotto, Penn State Hershey
Cancer Institute, Hershey, PA
Background: SG, both adenoid cystic (ACC) and mucoepidermoid (ME)
sub-types, are rare lung cancers. We choose to investigate the incidence of
these rare sub-types and assess their difference in presentation and
prognostic characteristics in comparison to adenocarcinomas (Ad) and
squamous cell carcinomas (SCC) during the same time period. Methods:
The SEER-17 database was used to collect data during the years 1988-
2008. Differences between populations were determined by the chi-square
test. Survival curves were generated as Kaplan-Meier techniques. Cox
proportional hazards test was used to compare survival differences. Results:
During the 20-year study period, ACC (n �100) and ME (n� 178)
accounted for 0.03% and 0.06% of NSCLCs. Mean follow-up was 34.5
months for all patients. In comparison to ACC, patients with ME were
significantly more likely to be younger (52 yr vs. 60yr), Asian(11.7% vs.
7%), have Stage I disease (62.9% vs 24.0%), and less likely to be in the
mainstem bronchi (17.2% vs. 6.3%). In comparison to patients with
patients presenting with either SCC or Ad, both ME and ACC were
significantly less likely to present with Stage IV disease (26.6% SCC,
41.29% Ad, 16.73% SG), have nodal involvement (35.1% SCC, 27.4%
Ad, 23.37% SG), and be older (70 SCC, 68 Ad, 58 years SG). Stratified by
stage and treatment, there was no survival (OS) or disease-specific survival
difference (DSS) between ACC and ME. The OS of the combined group of
ME and ACC was significantly better stage per stage than either Ad (Hazard
ratio (HR) range � 0.26- 041), and SCC (HR range � 0.17-0.56). Lung
Cancer-Specific survival at 2,3,5 years for surgically-resected Stage I ACC
and ME were 83.5%, 80.4%, and 80.4%; and 82.6%, 78.0% and 78%,
respectively. Conclusions: Patients with ACC and ME have rare sub-types of
lung cancer that present differently and have better survival than patients
presenting with either of the more common histologic sub-types (SCC and
Ad) of NSCLC. We encourage prospective, multi-institutional studies of
these rare sub-types so that care can be optimized. Optimal care may differ
for SG because of their stage per stage better prognosis than other NSCLCs.
7053 General Poster Session (Board #36D), Sat, 1:15 PM-5:15 PM
High-throughput targeted resequencing of lung adenocarcinoma. Presenting
Author: Byung Chul Kim, Personal Genomics Institute, Genome
Research Foundation, AICT, Suwon, South Korea
Background: The mutational profiles are crucial for cancer diagnosis and
classification, which lead to tailoring the best therapeutic strategy to each
patient. Here, we present target sequencing of 30 hot spot genes in lung
adenocarcinoma to identify new hot spot mutations in never-smoker,
female lung adenocarcinoma patients. Methods: We targeted 30 genes that
are known to be mutated frequently in lung adenocarcinoma. The exome
capture was done using selector technology and sequencing was done using
Illumina GA IIx Genome Analyzer. Exomic short reads from Illumina
Pipeline 1.4 were aligned to human genome (NCBI build 36) with BWA
0.5.0. Variations and small indels were called by Samtools 0.1.7 and
filtered by custom R scripts. Potential effects of these identified alterations
were assessed with sequence analysis. Results: On average, 1.5 billion
bases were uniquely mapped, and mean depth and coverage of exon regions
were 38X and 96%, respectively. Filtering of data against public SNP
database (dbSNP130), resulted in ~2,000 novel genetic alterations per
sample, including single nucleotide variations, and small insertion and
deletions in protein-coding regions. Among them, there were novel variants
in LTK and EPHA5 genes. Conclusions: Our results demonstrated the
feasibility of high-throughput mutation profiling with lung adenocarcinoma
samples. We identified novel variants in hot target genes, which may
provide an insight into the tumorigenesis signaling of lung adenocarcinoma.
7055 General Poster Session (Board #36F), Sat, 1:15 PM-5:15 PM
Would screening benefit 75- to 84-year-old patients with non-small cell
lung cancer (NSCLC)? Presenting Author: Jessica Lake, Penn State College
of Medicine, Hershey, PA
Background: The Lung Cancer Screening Trial has shown an overall survival
(OS) benefit and reduced lung cancer mortality in the 55-74 age group
(gp). We chose to evaluate whether NSCLC patients aged 75-84 are
increasing in the USA and whether they would benefit from aggressive
therapy. Methods: SEER-17 was used to calculate NSCLC rates during the
years 2000-2008. SEER-9 was used to estimate the proportional change in
both 55-74 and 75-84 gp from 1973-2008. OS was analyzed in a modern
population from SEER-17 (2004-2008) to assess the effects of increasingly
aggressive therapy (observation(Ob), radiation (RT) or lobectomy
(LB)) for a proposed screening population with T1N0 tumors. Chi-square
test and Cox Regression (CR) were used to evaluate OS. Paired T-tests
assessed changes in rates and proportions over time. Results: The 55-74 gp
rose from 64.4% in 1973 to 67.25% in 1984, but fell to 58.8% by 2008,
while the 75-84 gp rose from 12.1% in 1973 to 24% in 2008 (p�0.01),
similar in both sexes. The rates/100,000 have been increasing in the
75-84 gp (p�0.02), mainly in females (p�0.003) while the rates in the
55-74 gp did not vary, but fell for men (p�0.03). In the Ob gp (n�1344),
NSCLC was the most common cause of death (COD) in the 55-74 (29.8%)
and 75-84 gp (40.6%), more than all other CODs combined (median
survival (MS) � 11mn). CR revealed that OS was associated with the 55-74
gp (0.59) and females (0.62) (p � 0.001). In the RT gp (n�1870), MS was
14mn and lung cancer was the most common COD at 27.7% (55-74) and
28.8% (75-84), again more than all other CODs combined. CR found that
females (0.68) and black race (0.72) had better OS (p�0.017), but age
was not. MS was 24 mn in the LB group (n�9384). COD from NSCLC and
all other CODs was 8.2% and 6.1% (55-74) and 10.9% and 11.4%
(75-84). CR showed that 55-74 (0.36), females (0.58), and Asians (0.73)
had lower death rates (all p�0.015). Mean OS between the 55-74 (26.0)
and 75-84 (24.2) gp showed a small yet significant difference. Conclusions:
Rates and proportions of NSCLC have been steadily increasing in the 75-84
gp. These data show that COD by lung cancer decreased significantly with
increasingly aggressive treatment and treatment reduced the effects of age
gp on survival. We feel that screening may be of benefit to the 75-84 gp.
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