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

492s Lung Cancer—Non-small Cell Metastatic
7549 General Poster Session (Board #45G), Sat, 1:15 PM-5:15 PM
Phase III study (MONET1) of motesanib plus carboplatin/paclitaxel (C/P) in
patients with advanced nonsquamous non-small cell lung cancer (NSCLC):
Asian subgroup analysis. Presenting Author: Yukito Ichinose, National
Kyushu Cancer Center, Fukuoka, Japan
Background: MONET1 evaluated overall survival (OS) in patients (pts) with
nonsquamous NSCLC receiving motesanib (an oral VEGFR 1, 2 and 3,
PDGFR and Kit inhibitor) plus C/P compared with pts receiving placebo
plus C/P. Analysis of the total population (N�1090) showed that motesanib
� C/P did not significantly improve OS vs C/P alone (primary
endpoint). Here we present results of a subgroup analysis of Asian pts.
Methods: Asian pts (Japan, S. Korea, Philippines, Hong Kong, Taiwan,
Singapore) with stage IIIB/IV or recurrent nonsquamous NSCLC and no
prior systemic therapy for advanced NSCLC were analysed. Pts were
randomized to up to six 3-wk cycles of C (AUC 6 mg/mL·min) and P (200
mg/m 2 ) with either motesanib 125 mg QD (Arm A) or placebo QD (Arm B)
orally continuously. Results: 227 Asian pts (incl. 106 Japanese pts) with
nonsquamous NSCLC were randomized (Arm A/B, n�110/117); 198 had
adenocarcinoma (n�97/101). Median age was 60 y (range 30–78); 80%
had stage IV disease. At the time of analysis, 139 pts had died (118 pts
with adenocarcinoma). Pts received a median of 164 days of motesanib vs
125 days of placebo (vs 106 and 126 days in non-Asian pts). Median
follow-up was 63 wks. Efficacy results are shown in the table. Motesanib/
placebo-related AEs were seen in 94/74% of pts respectively; Gr �3
related AEs in 48/22%. Most common emergent AEs were (Arm A/B)
alopecia (78/76%), diarrhea (63/33%), and nausea (55/43%); gallbladder
disorders (Gr 1–2) were seen in 9/2% of pts. Gr �3 AEs more frequent in
Arm A vs B included neutropenia (36/22%) and hypertension (13/3%).
Emergent Gr 5 events were seen in (Arm A/B) 5/4% vs 16/11% in
non-Asian pts. Conclusions: In contrast to non-Asian pts, in the subgroup of
Asian pts with advanced nonsquamous NSCLC, motesanib plus C/P
treatment was associated with increased OS, PFS, and objective response
rates (ORR) compared with C/P alone, with no excess of treatment-related
mortality.
Asian subgroup All non-Asian pts
Motesanib �C/P (n�110) Placebo � C/P (n�117) Motesanib �C/P(n�431) Placebo � C/P (n�432)
Median OS (mos)
Median PFS (mos)
20.9*
7.0
14.5 10.9 10.7
† ORR (%) 62
5.3 5.5 5.4
† 27 34* 25
CR �1 0 �1 �1
PR 61 27 33 25
*p�0.05; †p�0.001 vs placebo � C/P
7551 General Poster Session (Board #46A), Sat, 1:15 PM-5:15 PM
A randomized phase II study of axitinib in combination with pemetrexed/
cisplatin (pem/cis) as first-line therapy for nonsquamous non-small cell
lung cancer (NSCLC). Presenting Author: Chandra Prakash Belani, Penn
State Hershey Cancer Institute, Hershey, PA
Background: Axitinib is a potent and selective second-generation inhibitor
of VEGF receptors 1, 2, and 3 that has promising single-agent activity in
advanced NSCLC. Efficacy and safety of axitinib (in 2 dosing schedules)
combined with pem/ciswere evaluatedfor non-squamous NSCLC. Methods:
Patients with confirmed stage IIIB, IV, or recurrent non-squamous NSCLC
and ECOG performance status (PS) 0 or 1 were stratified by gender and PS,
and randomized 1:1:1 to receive six 21-day cycles of axitinib continuously
plus pem/cis (arm I); axitinib on Days 2 through 19 followed by a 3-day
interruption plus pem/cis (arm II); or pem/cis alone (arm III). Axitinib was
administered at a starting dose of 5 mg BID. Pem/cis (500/75 mg/m2 ) was
infused on Day 1 of each cycle. Primary endpoint was progression-free
survival (PFS). Results: Baseline characteristics of patients in arm I
(n�55), arm II (n�58), or arm III (n�57) ranged between 59–62 yr
median age; 62–65% male; 71–85% White; 73–85% current/exsmokers;
and 43–47% PS 0. There were no significant differences in PFS
or overall survival (OS) between axitinib-containing arms I and II compared
with pem/cis alone, but objective response rates (ORR) were higher (Table).
Most common all causality grade 3 adverse events (AEs) in arm I, II, and III,
respectively, were hypertension (20%, 17%, 0%); neutropenia (18%,
10%, 9%); nausea (16%, 5%, 7%); vomiting (13%, 5%, 4%); fatigue
(11%,16%,16%); and anemia (7%, 14%, 9%). Grade 4 AEs observed in
�1 patient were asthenia and pulmonary embolism (2 patients each in arm
II). Conclusions: Axitinib combined with pem/cis was generally well tolerated,
but efficacy was not significantly better than pem/cis alone in
non-squamous NSCLC.
Median PFS (95% CI), mo
HR (95% CI) vs Arm III
P
Median OS (95% CI), mo
HR (95% CI) vs Arm III
P
ORR (95% CI), %
Treatment Difference, %
(95% CI) vs Arm III
P
Arm I Arm II Arm III
8.0 (6.5, 10)
0.892 (0.560, 1.423)
0.355
16.6 (12.6, 22.4)
1.079 (0.663, 1.756)
0.632
45.5 (32.0, 59.4)
19.2 (1.7, 36.6)
0.013
7.9 (6.2, 9.5)
1.019 (0.640, 1.623)
0.545
14.7 (11.5, 18.1)
1.391 (0.871, 2.222)
0.891
39.7 (27.0, 53.4)
13.4 (-3.7, 30.3)
0.069
7.1 (5.8, 9.2)
–
15.9 (11.1, –)
–
26.3 (15.5, 39.7)
–
7550 General Poster Session (Board #45H), Sat, 1:15 PM-5:15 PM
Final results of a randomized, double-blind, phase II study of gemcitabine
plus vandetanib or plus placebo in the treatment of advanced (stage
IIIB/IV) non-small cell lung cancer (NSCLC) elderly patients (ZELIG study
NCT00753714). Presenting Author: Cesare Gridelli, SG Moscati Hospital,
Avellino, Italy
Background: Vandetanib (V) is a once-daily oral inhibitor of VEGFR, EGFR
and RET signaling. Single-agent gemcitabine (G) is a standard of care
option for unselected patients (pts) unfit for doublet platinum based
chemotherapy. This study assessed the progression-free survival (PFS)
benefit of G�V compared to G plus placebo (P) in pts with advanced NSCLC
aged � 70 years. Methods: Eligible pts (stage IIIB/IV NSCLC; WHO PS 0-2;
all histologies; chemonaïve, aged �70) were randomized 1:1 to receive G
1200 mg/m2 i.v. day 1 and 8 of each 21-day cycle, up to 6 cycles plus V
100 mg/day or plus P until progression/toxicity. The primary objective was
PFS (80% power to detect a hazard ratio [HR] � 0.667). Secondary
endpoints included overall survival (OS), objective response rate (ORR),
disease control rate (DCR), and safety. Results: Between Oct 2008-May
2010, 124 pts (median age 75 yrs (70-84); 72.6% male; 57.2% WHO PS
0-1; 74.2% past/never-smoker; 58.1% adenocarcinoma; 89.5% stage IV)
were randomized to G�V (n�61) or G�P (n�63). Baseline characteristics
were similar in both arms. At data cut-off (Apr11), 87.9% pts
progressed and 73.4% pts had died. PFS was significantly prolonged for
G�V (HR�0.729; 95% CI 0.484-1.096; p�0.0417), median PFS
G�V�6.0 months, G�P�5.5 months. No differences were seen in ORR
(14.8% and 12.7%; p � 0.74), DCR (72.1% and 66.7%; p �0.51), OS
(HR�1.024 [95% CI 0.667-1.571] p�0.8960), proportion of pts alive at
1-year G�V�31.1% and G�P�30.2% (p�0.90). Adverse events (AEs)
observed for V 100 mg were generally consistent with previous NSCLC
studies of V 100 mg. Common AEs (any grade) occurring with a greater
frequency in the G�V arm included skin toxicity (34.4% vs 15.9%) and
hypertension (9.8% vs 3.2%). Diarrhea and neutropenia were similar in
both arms (14.8% and 14.3%; 19.7% and 19.0%). Conclusions: Despite a
marginally statistically significant improvement in PFS the study did not
met the primary and secondary end points. The combination G�V was well
tolerated in this clinical setting.
7552 General Poster Session (Board #46B), Sat, 1:15 PM-5:15 PM
Molecular marker analysis of SWOG S0636, a phase II trial of erlotinib and
bevacizumab in never-smokers with advanced NSCLC. Presenting Author:
Philip C. Mack, University of California, Davis, Sacramento, CA
Background: S0636 investigated the combination of erlotinib and bevacizumab
in never-smoking NSCLC patients with confirmed adenocarcinoma
histology (H. West ASCO 2011). Patient eligibility was not restricted by
molecular selection. Median PFS and OS were encouraging at 8 and 26
months. An analysis of molecular markers was undertaken, focusing
initially on the EGFR pathway. Methods: EGFR analysis included gene copy
number, mutation and protein expression. Copy number was conducted by
FISH using the Colorado scoring system. An immunohistochemistry H score
was developed for EGFR protein expression analysis, ranging from 0 to
400. Specimens were evaluable from 42 of the 85 eligible patients.
Results: FISH positivity was identified in 17/35 pts (49%), 11 with high
polysomy and 6 with true gene amplification. EGFR activating mutations
were seen in 10/33 pts (30%). IHC H-score �200 was observed in 17/40
pts (43%). All EGFR markers were significantly correlated with one
another. In the EGFR WT subgroup, FISH-positive patients outperformed
FISH-negative pts (mPFS 20 vs, 6 months, p�0.06). Conclusions: Careful
analysis of EGFR markers (mutation, FISH and IHC) identified S0636
patients with favorable PFS and encouraging trends for OS. EGFR FISH and
IHC provided additional predictive information beyond that of EGFR
mutation status. Supported in part by DHHS: CA32102 and CA38926, and
in part by Genentech.
Group N mPFS (mos) p value mOS (mos) 2-Year OS p value
FISH positive 17 20 NR 0.82
FISH negative 18 6 0.02 17 0.39 0.08
EGFR mutant 10 36 NR 0.53
EGFR wild type 23 8 0.09 26 0.57 0.69
FISH � OR mutant 20 20 NR 0.72
FISH – AND WT 13 6 0.03 15 0.40 0.08
IHC: 0-100 11 6 ref. 18 0.25 ref.
101-200 12 8 0.26 NR 0.61 0.27
201-400 17 19 0.03 NR 0.74 0.06
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