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

496s Lung Cancer—Non-small Cell Metastatic
7566 General Poster Session (Board #47H), Sat, 1:15 PM-5:15 PM
Rare and complex mutations of epidermal growth factor receptor (EGFR)
and efficacy of tyrosine kinase inhibitor (TKI) in patients with non-small
cell lung cancer (NSCLC). Presenting Author: Bhumsuk Keam, Department
of Internal Medicine, Seoul National University Hospital, Seoul, South
Korea
Background: Other than in-frame deletional mutation (MT) in exon 19 and
Leu858Arg point MT in EGFR gene, there are many rare and complex MT.
The purpose of this study was to investigate was to clarify the clinical
significance of rare and complex MT, and the efficacy of EGFR TKI in these
patients. Methods: Rare MTs were defined any MT other than deletional MT
in exon 19, Leu858Arg in exon 21, and Thr790Met in exon 20. Complex
MT was defined two different EGFR MTs co-occurring within the single
tumor sample. We have analyzed consecutive database of NSCLC patients
who were treated with either gefitinib or erlotinib at Seoul National
University Hospital between Jan. 2002 and Dec. 2011. For analysis of
EGFR MT, coding sequences from exon 18 to 21 were amplified by nested
PCR and subjected to direct sequencing methods. Results: Among the
1,159 TKI treated patients, 301 patients had EGFR MT (177 patients
(58.8%) with del-19, 104 patients (34.6%) with Leu858Arg, and 20
patients (6.6%) with rare MT). Twenty-three (7.6%) patients have complex
MT, and 55 (18.3%) patients have Gln787Gln polymorphism particularly
associated with Leu858Arg MT. Identified rare MT were follows; exon 18:
Leu692Phe, Glu707Lys, Glu709Gly, Lys714Asn, Gly7Ala, Thr725Thr,
exon 19: Ala755Asp Lys737Thr, exon 20: Val786Met, exon21: Ala871Gly,
Gly873Gln, Leu833Val, Val834Leu, Arg836Cys, Pro848Leu, Ala859Thr,
Leu861Gln. When categorizing 3 groups (group A: classic MT alone, group
B: complex MT with classic � rare MT, group C: rare MT alone or complex
MT with rare MTs), response rate (RR) to TKI was different between each
groups (RR� 78.7% in group A vs. 69.2% in group B vs. 38.5% in group C,
respectively, P � 0.001). Progression-free survival (PFS) was also poorer in
rare MT (median PFS: 12.1 mo vs. 7.6 mo vs. 2.1 mo, respectively, P�
0.020,). Gln787Gln polymorphism of exon 21 was not associated with RR
or PFS (P� 0.101, P� 146, respectively) Conclusions: In this large case
series, NSCLC patients who harboring rare MT other than del-19 and
Leu858Arg, does not seems response to EGFR TKI. However, complex MT
with the classical MT showed similar treatment efficacy toward EGFR TKI
with that of classical MT alone.
7569 General Poster Session (Board #48C), Sat, 1:15 PM-5:15 PM
Phase I/II study of amrubicin and nedaplatin in patients with untreated,
advanced non-small cell lung cancer. Presenting Author: Hiroaki Senju,
National Nagasaki Medical Center, Ohmura, Japan
Background: We conducted a phase I/II study of combination chemotherapy
with nedaplatin (CDGP) and amrubicin (Amr) for patients with untreated,
advanced non small-cell lung cancer (NSCLC). Methods: Eligible patients
were having adequate organ function and PS of 0-1. CDGP was given on day
1 and amrubicin on days 1, 2 and 3. The treatment was repeated every 3
weeks. We fixed the dose of CDGP as 100 mg/m2, and escalated the dose of
amrubicin from a starting dose of 25 mg/m2 by 5mg/m2 per each levels
until the maximum tolerated dose (MTD). The MTD was defined as the dose
level at which at least two of three or two of six patients experienced a
dose-limiting toxicity (DLT). Results: Between June 2009 and May 2011,
36 patients were enrolled. In the phase I study, two DLTs occurred in six
patients at level 2; dose level 1 was therefore recommended (25 mg/m2
Amr, 100mg/m2 CDGP). DLTs included cerebral infarction and grade 4
thrombocytopenia. In the phase II study, including phase I study, a total of
36 patients were enrolled and 132 cycles of chemotherapy were conducted.
Grade 3 or 4 neutropenia, grade 3 anemia and grade 3 or 4
thrombocytopenia occurred in 75%, 16.6% and 19.4% in all cycles,
respectively. Febrile neutropenia occurred in 4cycles (3%) but all of them
were controllable. Eighteen patients achieved a partial response and the
overall response rate was 51.4%. Conclusions: Combination of CDGP and
Amr was highly effective and well tolerable in patients with untreated,
advanced NSCLC.
7568 General Poster Session (Board #48B), Sat, 1:15 PM-5:15 PM
A phase II study of erlotinib followed by chemotherapy on progression in an
unselected population of advanced non-small cell lung cancer (NSCLC)
patients. Presenting Author: Leora Horn, Vanderbilt-Ingram Cancer Center,
Nashville, TN
Background: Erlotinib is now accepted as first line therapy for advanced
NSCLC patients with EGFR mutated tumors. However, some patients with
EGFR wild-type tumors may benefit as well, and there are no accepted
biomarkers to define this subset of patients or to define which patients
benefit from chemotherapy. We conducted a single arm phase II trial of
erlotinib followed by chemotherapy on progression (carboplatin � paclitaxel
�/- bevacizumab) in treatment naïve patients with stage IV NSCLC.
Methods: In this multicenter prospective phase II trial, patients with stage
IV NSCLC were eligible for enrollment. Blood, frozen tissue and FFPE
biopsies for molecular analysis were mandatory at the time of study entry
and optional at the time of progression on erlotinib. Additional eligibility
included ECOG performance status (PS) 0-2, measurable disease, and
adequate marrow, renal and hepatic function. Patients with stable treated
brain metastases were allowed. Patients were treated with erlotinib 150 mg
daily until disease progression at which time they underwent a biopsy and
were switched to carboplatin/paclitaxel �/- bevacizumab. Disease status
was assessed after 4 weeks of erlotinib to detect early progression. Results:
From 10/07 to 06/11, 127 patients were enrolled: 59% male, 90%
Caucasian, 6% African American, 4% Asian, 30% never smokers. 7
patients failed screening. Among evaluable patients on erlotinib, 13% had
PR, 48% SD, and 27% PD. Median PFS on erlotinib was 4.7 months (95%
CI 3.5 to 8.3 months). In patients who went on to receive chemotherapy on
protocol, 24% had PR, 27% SD, and 20% PD. In patients who went on to
receive chemotherapy on protocol median progression-free survival (PFS)
on chemotherapy was 8.1 months (95% CI 5.5 to 10.9 months). Among
the 55 patients who did not receive chemotherapy, 23 had a decline in PS,
14 patients refused, 2 patients enrolled on another protocol, and 6 patients
had other therapy. Conclusions: This is the first study to report on PFS in
unselected NSCLC patients following first line therapy with erlotinib.
Translational studies on this large prospectively collected cohort of tissue
samples prior to initiation of erlotinib are ongoing.
7570 General Poster Session (Board #48D), Sat, 1:15 PM-5:15 PM
Older patient participation in SWOG lung cancer trials: Comparative
analysis from 1993 to 2008. Presenting Author: Paul Joseph Hesketh,
Lahey Clinic, Tufts University School of Medicine, Burlington, MA
Background: In 1999, SWOG published a study demonstrating the underrepresentation
of patients 65 years and older on clinical trials (Hutchins
NEJM). A second report published in 2006 demonstrated increasing
proportions of patients � 65 years (31% 1997-2000; 38% 2001-2003)
being enrolled into SWOG trials (Unger JCO). Older patient enrollment was
still disproportionately low compared to the US cancer population. The
current analysis focuses on patients with lung cancer from 1993-2008.
Methods: The proportions of enrollment onto SWOG lung cancer treatment
trials by age (65-69, 70-79, �80 years) and gender were computed for
4-year time intervals between 1993 and 2008; corresponding rates in the
US were derived from US Census and National Cancer Institute SEER data.
Proportions in the SWOG trials were compared to the SEER proportions
using a 1-sample binomial test of proportions. Time trends within SWOG
were evaluated using linear regression. Results: The proportion of patients
65-69 was significantly higher than the US population between 1993 and
2004, but was not significantly different after 2004. Proportions of
patients on SWOG trials 70-79 years old and � 80 were significantly
smaller than the US population. Females were underrepresented from
1993-2004. Between 2005 and 2008 female enrollment was not significantly
different from the US population. Conclusions: Currently, the
proportion of patients 65-69 years of age and of female gender enrolled in
SWOG trials is representative of the general lung cancer population.
Although some progress has been made in increasing trial participation of
patients � 70, enrollment remains disproportionately low. The disparity is
most evident in patients � 80. Continued efforts are needed to increase
older patient participation in lung cancer trials. Supported in part by PHS
Cooperative Agreement grants awarded by the National Cancer Institute:
DHHS, CA32102 and CA38926.
1993-1996 1997-2000 2001-2004 2005-2008
SEER SWOG SEER SWOG SEER SWOG SEER SWOG
Age 65-69 16% 20%� 16% 19%� 16% 19%� 16% 17%
Age 70-79 34% 18%� 35% 18%� 36% 24%� 37% 23%�
Age > 80 16% 1%� 17% 1%� 18% 3%� 20% 4%�
Female gender** 42% 34%� 45% 39%� 47% 39%� 49% 46%
� p � -.01; ** time trend p�0.05.
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