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

480s Lung Cancer—Non-small Cell Metastatic
LBA7500 Oral Abstract Session, Mon, 3:00 PM-6:00 PM
LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus
pemetrexed and cisplatin as first-line treatment for patients with advanced
adenocarcinoma of the lung harboring EGFR-activating mutations. Presenting
Author: James Chih-Hsin Yang, National Taiwan University Hospital,
Taipei, Taiwan
The full, final text of this abstract will be available at
abstract.asco.org at 12:01 AM (EDT) on Monday, June 4,
2012, and in the Annual Meeting Proceedings online
supplement to the June 20, 2012, issue of Journal of
Clinical Oncology. Onsite at the Meeting, this abstract will
be printed in the Monday edition of ASCO Daily News.
7502 Oral Abstract Session, Mon, 3:00 PM-6:00 PM
SELECT: Randomized phase III study of docetaxel (D) or pemetrexed (P)
with or without cetuximab (C) in recurrent or progressive non-small cell
lung cancer (NSCLC) after platinum-based therapy. Presenting Author:
Edward S. Kim, University of Texas M. D. Anderson Cancer Center,
Houston, TX
Background: SELECT investigated whether the addition of C to standard
chemotherapy improved progression-free survival (PFS) in patients (pts)
with recurrent or progressive NSCLC after failure of platinum-based
therapy. Methods: SELECT was a multicenter, open label, randomized
phase III trial. Per investigator choice, pts received either P (500 mg/m2 )or
D (75 mg/m2 ) on day 1 and then were randomized within each group to
chemotherapy plus C (400/250 mg/m2 ) (initial/weekly) or chemotherapy
alone. Therapy was given for up to six 3-week cycles; pts randomized to C
continued weekly monotherapy until disease progression or unacceptable
toxicity. The primary objective was PFS for PC vs. P as determined by an
Independent Review Committee (IRC). Secondary endpoints included
overall survival (OS), objective response rate (ORR) and duration of
response (DOR) by IRC, and safety. Preplanned subgroup analyses for
epidermal growth factor receptor (EGFR) staining intensity by immunohistochemistry
and histology were performed. Results for PC vs. P only are
presented. Results: Between Jan 2005 and Feb 2010, 938 total pts were
randomized. Baseline demographics were comparable between PC (n�301)
andP(n�304): median age 64 years; male 60%; Caucasian 88%; KPS
80-100/60-70 84%/16%; squamous/non-squamous 24%/76%. Median
PFS (months) PC: 2.89 and P: 2.76 (hazard ratio [HR] �1.03 [95%
confidence interval (CI)�0.87-1.21]; p�0.76). Median OS (months) PC:
6.93 and P: 7.79 (HR�1.01 [95% CI�0.86-1.20]; p�0.86). ORR PC:
6.6% and P: 4.3% (odds ratio �1.59 [95% CI�0.78-3.26]; p�0.20).
Median DOR (months) PC: 4.17 and P: 6.93 (HR�1.58 [95% CI�0.74-
3.36]; p�0.24). There were no statistical differences in efficacy based on
histology or EGFR staining intensity. More drug-related AEs/SAEs were
observed in the PC arm, with differences mainly attributable to skin
toxicities, GI (diarrhea/stomatitis), and hypomagnesemia. Conclusions: The
addition of C to P did not improve efficacy in this pt population. Further
biomarker analyses are planned. The safety profiles for C and P were
consistent with existing data and no new safety signals were observed.
LBA7501 Oral Abstract Session, Mon, 3:00 PM-6:00 PM
TAILOR: Phase III trial comparing erlotinib with docetaxel in the secondline
treatment of NSCLC patients with wild-type (wt) EGFR. Presenting
Author: Marina Chiara Garassino, U.O. Oncologia Medica, A.O. Fatebenefratelli
e Oftalmico, Milan, Italy
The full, final text of this abstract will be available at
abstract.asco.org at 12:01 AM (EDT) on Monday, June 4,
2012, and in the Annual Meeting Proceedings online
supplement to the June 20, 2012, issue of Journal of
Clinical Oncology. Onsite at the Meeting, this abstract will
be printed in the Monday edition of ASCO Daily News.
7503 Oral Abstract Session, Mon, 3:00 PM-6:00 PM
Phase II double-blind, randomized study of selumetinib (SEL) plus
docetaxel (DOC) versus DOC plus placebo as second-line treatment for
advanced KRAS mutant non-small cell lung cancer (NSCLC). Presenting
Author: Pasi A. Janne, Dana-Farber Cancer Institute, Boston, MA
Background: KRAS mutations are the most common (~20%) oncogenic
alteration in NSCLC. There are no effective targeted therapies for this
subset of NSCLC. Selumetinib (AZD6244, ARRY-142866) inhibits MEK1/2
signaling downstream of KRAS. We prospectively evaluated SEL � DOC vs
DOC � placebo in advanced KRAS mutant NSCLC based on preclinical
observations (NCT00890825). Methods: Patients (pts) with stage IIIB-IV,
KRAS mutant NSCLC, who had received prior chemotherapy, received iv
DOC 75 mg/m2 , and po SEL 75 mg or placebo BD. The primary endpoint
was overall survival (OS); secondary endpoints included: progression-free
survival (PFS), objective response rate (RR), duration of response, change
in tumor size, proportion of patients alive and progression-free at 6 mo, and
safety and tolerability. Results: Between April 2009 and June 2010, 422
pts were screened across 67 centers in 12 countries; 113 had KRAS
mutant NSCLC and 87 were randomized (DOC, 43; SEL/DOC, 44).
Baseline characteristics were balanced (DOC vs SEL/DOC): WHO PS 0,
49%/48%; Female, 54%/52%; KRAS codon 12, 90%/93%. Median
number of cycles: DOC, 4; SEL/DOC, 5. Most frequent grade 3/4 hematologic
toxicity (DOC vs SEL/DOC): neutropenia (54.8%/67.4%), febrile
neutropenia (0%/15.9%); most frequent grade 3/4 non-hematologic toxicity:
dyspnea (11.9%/2.3%) asthenia (0%/9.1%), respiratory failure (4.8%/
6.8%), acneiform dermatitis (0%/6.8%). Discontinuation due to AEs was
similar: 18.2% SEL/DOC vs 11.9% DOC. OS was longer for SEL/DOC vs
DOC (9.4 mo vs 5.2 mo; 56 events, median follow-up 219 days) but did not
reach statistical significance; hazards were non proportional (HR 0.80;
80% CI 0.56, 1.14; 1-sided p�0.2069). All secondary endpoints,
including RR (DOC 0%, SEL/DOC 37%; p�0.0001) and PFS (DOC 2.1 mo,
SEL/DOC 5.3 mo; 71 events; HR � 0.58; 80% CI 0.42, 0.79; 1-sided
p�0.0138), were significantly improved for SEL/DOC vs DOC. Conclusions:
This is the first prospective study to demonstrate a clinical benefit of a
targeted therapy (SEL � DOC) for patients with KRAS mutant cancer of any
type. Our findings could have implications for the treatment of NSCLC and
other KRAS mutant cancers.
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