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

7587 General Poster Session (Board #50E), Sat, 1:15 PM-5:15 PM
Sorafenib and continued erlotinib or sorafenib alone in patients with
advanced non-small cell lung cancer progressing on erlotinib: A randomized
phase II study of the Sarah Cannon Research Institute (SCRI).
Presenting Author: Victor Gian, Tennessee Oncology, PLLC/Sarah Cannon
Research Institute, Nashville, TN
Background: Erlotinib is an oral epidermal growth factor receptor kinase
inhibitor used in the treatment of advanced non-small-cell lung cancer
(NSCLC). Resistance develops in patients (pts) who initially respond to
erlotinib leading to progressive disease (PD). Sorafenib is an oral inhibitor
of vascular endothelial and platelet-derived growth factor receptors and Raf
kinases which play important roles in PD. This randomized phase II study
evaluated the role of sorafenib and continued erlotinib or sorafenib alone in
pts with progressive NSCLC following initial benefit with erlotinib. Methods:
Eligible pts had IIIB/IV NSCLC, an ECOG PS 0-2, and had received �2
lines of therapy with the last being single-agent erlotinib. Pts must have PD
following clinical benefit (complete/partial response/stable disease) from
erlotinib for �8 weeks. Pts were randomized 1:1 to continue erlotinib at the
dose administered at the time of PD with the addition of sorafenib 400 mg
orally twice daily (Arm A) or to sorafenib alone (Arm B). Cycles were 28 days
with restaging every 2 cycles. The primary endpoint was progression-free
survival (PFS). Results: 52 pts were enrolled from 2/2008 to 3/2011 (A 24;
B 28). Baseline characteristics were balanced between arms and included:
median age 65 years (41-87); 65% female; 69% adenocarcinoma/large
cell; and 96% PS �2. 41% of pts were either never smokers or smoked
�100 cigarettes/lifetime. Pts received a median of 8 weeks of treatment
per arm (0.6–67 weeks). The median PFS was 3.1 (95% CI 1.7-3.7) and
2.3 (1.7-3.6) months for A and B, respectively (p�.84). There were no
grade 3/4 hematologic toxicities in either arm except grade 3 anemia in 1 pt
(A). Severe nonhematologic toxicities in �5% included: fatigue 17%(A)/
7%(B); diarrhea 17%/0; dehydration 13%/7%; hand-foot skin reaction
8%/8%, and anorexia 4%/7%. Conclusions: Sorafenib has modest activity
when used in combination with erlotinib or as a single agent in pts with PD
following benefit with erlotinib alone. Additional study to identify potential
subsets of refractory pts who might derive the greatest benefit from
sorafenib are warranted.
7589 General Poster Session (Board #50G), Sat, 1:15 PM-5:15 PM
ALK and MET genes in advanced lung adenocarcinomas: The Lung Cancer
Mutation Consortium experience. Presenting Author: Marileila Varella-
Garcia, Department of Medicine/Medical Oncology, University of Colorado
Cancer Center, Aurora, CO
Background: The Lung Cancer Mutation Consortium (LCMC) consisting of
14 US Cancer Centers was established to evaluate a panel of molecular
mutations in advanced lung adenocarcinoma. ALK gene fusions and MET
gene amplification were assessed by FISH in CLIA certified laboratories.
Methods: Molecular tests were performed in stage IIIB or IV lung adenocarcinoma.
To date, FISH assays have been completed in 901 patients for ALK
(ALK break-apart, Abbott Molecular) and in 654 patients for MET (in
house/Abbott Molecular reagents). ALK� specimens were defined by split
3’ALK/5’ALK signals (gap �2 signal diameters) or single 3’ALK signals in
�15% of tumor cells. MET gene amplification (MET�) was defined by ratio
mean MET/mean CEP7 �2. Results: The ALK� patient subset (N�75,
8.3%) compared to the ALK- had significantly lower age at diagnosis (52
vs. 60, p�0.001) and less frequent heavy smoking history (61% neversmokers
among ALK� vs. 31% among ALK-, p�0.001; pack-year for
current/former smokers 17 vs. 40, p�0.003). Liver metastases were
significantly more frequent among ALK� than ALK- (23% vs.10%,
p�0.004); no difference was detected in bone, brain and adrenal gland
metastases. MET� (N�29, 4.4%) was significantly associated with female
sex (72% female among MET� vs. 39% among MET-, p�0.001) and
marginally more frequent in patients with adrenal metastasis; no difference
was detected for age at diagnosis and smoking history. Follow-up on 73
ALK� patients indicated that 56% received crizotinib as targeted therapy.
Response was unknown in 8% and unreportable in 22% patients enrolled
in ongoing randomized trials. Among patients with evaluable response,
complete response, partial response, stable disease, and progressive
disease were found respectively in 3%, 66%, 28%, and 3%. Conclusions:
The LCMC successfully tested ALK and MET FISH in a large number of lung
adenocarcinomas. It was demonstrated that directing positive patients to
specific interventions is feasible, and that grouping of testing and trials
within consortia may maximise relevant trial accrual in rare molecular
subtypes. Supported by NCI-GO award. Submitted on behalf of the LCMC.
Lung Cancer—Non-small Cell Metastatic
501s
7588 General Poster Session (Board #50F), Sat, 1:15 PM-5:15 PM
Clinical characteristics of KRAS mutations in NSCLC and their impact on
outcomes to first-line chemotherapy. Presenting Author: Mohit Butaney,
Dana-Farber Cancer Institute, Boston, MA
Background: KRAS is one of the most commonly mutated oncogenes in
non-small cell lung cancer (NSCLC). While the impact of EGFR mutations
and EML4-alk translocations has been well-described, there is limited
information about the impact of these somatic mutations on response to
chemotherapy. Methods: We retrospectively reviewed the demographics
and clinical outcomes of patients with KRAS mutations and compared
these to patients who were KRAS wild-type (WT). Eligible pts received
1st-line IV chemo for stage IV NSCLC at DFCI and had known information
about both KRAS and EGFR status. Since the biology and impact of EGFR
mutations on response to chemo is well-described, we excluded such pts
from the analysis. The primary endpoint was progression-free survival (PFS)
with first-line chemo; secondary endpoints included radiographic response
rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there
were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar
in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89%
white/6% black, 5% other; WT 86% white,/6% black/8% other), histology
(K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of
pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS
pts were less likely to be never or light smokers (4% vs 33% for WT).
Nonsmokers were more likely to harbor KRAS transition rather than
transversion mutations (3 transition, 1 transversion), while the converse
held for smokers (51 transversions, 8 transitions). Median PFS was similar
for KRAS vs WT (K .65 vs WT 4.8 months, p�0.81). RR (29% for both
groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5
vs WT 12.1 months, p�.525) were also similar. Outcomes of KRAS pts to
2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT
patients in this setting. There was no significant difference in outcomes
based on gender, smoking status, drug received (pemetrexed-based vs
taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS
mutations experience similar outcomes to standard chemotherapy as those
who are wild-type for EGFR and KRAS. Going forward, these data can serve
as a reference for control arms of KRAS-specific randomized trials.
7590 General Poster Session (Board #50H), Sat, 1:15 PM-5:15 PM
Weekly nab-paclitaxel in combination with carboplatin as first-line therapy
in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC).
Presenting Author: Mark A. Socinski, University of Pittsburgh Medical
Center, Pittsburgh, PA
Background: The median age of advanced NSCLC pts in the US is 71 years;
yetelderly pts (�70 years) are generally undertreated, with only �30%
receiving systemic therapy. Hence, better, more tolerable therapeutic
options are needed for this cohort. In a phase III trial nab-paclitaxel (nab-P,
130 nm albumin-bound paclitaxel particles) � carboplatin (C) vs solventbased
paclitaxel (sb-P) � C, significantly improved ORR, the primary
endpoint (25% vs 33%, P � 0.005), with a 1-month improvement in OS (P
� NS) and improved safety. This analysis evaluated efficacy and safety in
pts �70 and �70 years old. Methods: Pts with untreated stage IIIB/IV
NSCLC and with an ECOG score of 0/1 were randomized 1:1 (stratified by
age [�70 vs �70 years], region, stage, gender, and histology) to C AUC 6
day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 or sb-P 200 mg/m2 day
1 q 21 days. ORR and progression-free survival (PFS) were determined by
blinded centralized review. Results: Of the phase III study population, 15%
were elderly (156/1052; 74 pts in the nab-P/C and 82 in the sb-P/C arms).
Most elderly pts were male (72%), Caucasian (71%), and had stage IV
disease (64%). In pts both �70 and �70 years old, ORR was higher in the
nab-P/C vs sb-P/C arm (�70: 34% vs 24%, P � 0.196; �70: 32% vs
25%, P � 0.013). In pts �70 years old, PFS trended in favor of nab-P/C
(median 8.0 vs 6.8 months, HR: 0.687, P � 0.134); OS was significantly
improved (median 19.9 vs 10.4 months, HR: 0.583, P � 0.009). In
contrast, PFS (6.0 vs 5.8 median months, HR: 0.903, P � 0.256) and OS
(11.4 vs 11.3 median months, HR: 0.999, P � 0.988) were similar for
both treatment arms in pts �70 years old. Adverse events were similar in
pts �70 years old vs the entire study population, with less grade 3/4
neutropenia (P � 0.05) and neuropathy (P � 0.05) and increased
thrombocytopenia (P � NS) and anemia (P � 0.05) in the nab-P/C vs
sb-P/C arms. In pts �70 years old, patient-reported FACT-taxane subscales
revealed significantly less neuropathy, pain, and hearing loss in the nab-P/C
vs sb-P/C arms (P � 0.001). Conclusions: In elderly pts with advanced
NSCLC, nab-P/C as first-line therapy was well tolerated and led to improved
ORR and PFS, with significantly longer OS vs sb-PC.
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