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

498s Lung Cancer—Non-small Cell Metastatic
7575 General Poster Session (Board #49A), Sat, 1:15 PM-5:15 PM
Prospective randomized phase II trial of oral vinorelbine (NVBo) and
cisplatin (P) or pemetrexed (Pem) and P in first-line metastatic or locally
advanced non-small cell lung cancer (M or LA NSCLC) patients (pts) with
nonsquamous (non SCC) histologic type: NAVoTRIAL01—Preliminary
results. Presenting Author: Jaafar Bennouna, Institut de Cancerologie de
l’Ouest/Site René Gauducheau, Nantes, France
Background: NVBo�P is considered as a standard treatment (trt) in M or LA
NSCLC. The recent approval of Pem�P as front line chemotherapy (CT) for
non-SCC demonstrates that today, histology could become a “new guidance”
to treat patients (pts). Phase III trial (Scagliotti. JCO 2008) showed
efficacy of Pem�P in patients with non-SCC pts. Moreover, the higher
chemosensitivity of non-SCC is recognised and reported with other chemotherapies
(Ardizzoni.JNCI 2007). In GLOB 3 study, NVBo�P also showed
better survival in adenocarcinoma (11.7m) than in SCC (8.9m) (Tan.Ann of
Oncol 2009). This trial was set up to assess the efficacy of NVBo�P
compared to Pem�P for pts with non-SCC histological type. The primary
end-point was disease control rate (DCR) including overall response rate
(ORR) and stable disease (SD). Methods: Pts were randomised to receive
NVBo 80 mg/m² D1D8 (60 at Cycle 1) � P 80 mg/m² D1 q3w or Pem 500
mg/m² � P 75 mg/m² D1 q3w. After 4 cycles of trt, for pts showing a
disease control, single agent as continuation maintenance (CM) was
proposed until progression or toxicity. Given that Pem�P is now considered
as a reference trt in non-SCC, pts were randomised on a 2/1 basis and
stratified according to stage (IIIB - IV - relapse), non-SCC confirmed by
histology or cytology, gender, smoking status and centre. Results: From
10/09 to 02/11, 153 pts were randomised to receive NVBo�P (102 pts) or
Pem�P (51 pts). The efficacy between the 2 arms is similar: The ORR/DCR
(Recist 1.1) after 4 cycles of trt are 26%/75% in the NVBo arm (100 eval
pts in ITT population) and 24%/78% in the Pem arm (50 eval pts in ITT
population). At the end of December 2011, 7 patients are still treated in
CM: 5 pts in the NVBo arm and 2 pts in the Pem arm. Conclusions: The2CT
regimen, NVBo�P orPem�P have a similar efficacy in terms of ORR/DCR
for pts with advanced non-SCC NSCLC. These results appear to be in line
with the published data. As the analysis is currently in progress, final
results including safety data, PFS and OS will be presented during the
meeting.
7577 General Poster Session (Board #49C), Sat, 1:15 PM-5:15 PM
The relevance of stable disease (SD) as a surrogate end-point in advanced
non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) as
the second/third line. Presenting Author: Francesco Grossi, Lung Cancer
Unit, National Institute for Cancer Research, Genova, Italy
Background: SD has often been viewed as a result with an uncertain clinical
value.With the advent of E in advanced NSCLC, increasing numbers of
patients (pts) achieve SD as a best response. A common observation in
clinical practice is that a high proportion of patients receiving E have
durable SD.The aim of this analysis was to compare the progression-free
survival (PFS) and overall survival (OS) in pts with advanced NSCLC who
achieved confirmed SD or complete/partial response (CR�PR) after second/
third line treatment with E. Methods: Data from 684 Italian pts from the
TRUST trial (Tiseo M et al. Lung Cancer 2008) were analyzed. E was
administered orally at 150 mg per day and was continued until disease
progression, development of unacceptable toxicity or patient’s refusal. We
define confirmed SD (cSD) if the patients’ PFS was �5 months (response to
E was evaluated per protocol every two months) and reconfirmed SD (rSD) if
the patients’ PFS was �8 months. Results: Pts’ characteristics included the
following: median age, 67 years (31-89); females/males� 219/465 pts
(32%/68%); never/former smokers� 191/493 pts (28%/72%); squamous/
adeno/BAC/large cell/NOS� 163/361/26/21/113 pts (24%/53%/4%/3%/
16%); ECOG PS 0-1/2-3� 557/127 pts (81%/19%). In 83 pts (12%), E
was administered as the first-line therapy in pts who were unable to receive
chemotherapy; 305 pts (45%) had received 1 prior line of chemotherapy,
and 296 pts (43%) had received 2 prior lines of chemotherapy. A total of
428 pts were evaluable for a response: 44 pts (10%) exhibited CR�PR,
226 pts (53%) attained SD, which consisted of 139 pts (32%) with cSD
and 83 pts (19%) with rSD. The median PFS estimates (with 95% CI) were
13.1 months (9.8-16.4) for CR�PR pts, 9.9 months (8.2-11.4) for cSD
pts and 14 months (12-16) for rSD. The median OS estimates (with 95%
CI) were 24.0 months (17-31) for CR�PR pts, 17.9 months (14.4-21.5)
for cSD pts and 24.9 months (18.1-31.7) for rSD. Conclusions: Our
findings are the first to demonstrate the relevance of achieving stable
disease with E treatment. Pts obtaining cSD or rSD had durable PFS and
OS comparable, particularly for rSD, with PFS and OS of those having
CR�PR.
7576 General Poster Session (Board #49B), Sat, 1:15 PM-5:15 PM
Difference in incidence and pattern of salvage treatment after failure to
first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-
TKI) monotherapy and standard cytotoxic chemotherapy in pts with
advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations:
Okayama Lung Cancer Study Group experience. Presenting Author: Yuka
Kato, Okayama University Hospital, Okayama, Japan
Background: EGFR-TKI (E) therapy yielded a better PFS than standard
cytotoxic chemotherapy (C) therapy and a comparable OS in untreated pts
with EGFR-mt tumors, suggesting each of the treatments is now crucial for
such subpopulation. But, it has not been fully evaluated yet which of each
should be initiated first, and to what degree both of two are actually
administered in early line setting in the treatment course. We here
investigated a potential difference in incidence and pattern of delivery of
subsequent crossover therapy after failure to each of the treatments in pts
with EGFR-mt tumors. Methods: Consecutive 79 pts with advanced EGFR-mt
NSCLC were retrospectively assessed who underwent E therapy (n � 39) or
standard C therapy (n � 40) in the 1st-line setting between 2007 and
2011. Results: In E group 16 (41%) of 39 pts were still on 1st-line E
therapy. Nine (39%) of the remaining 23 could not receive standard C
therapy after failure to E therapy due to symptomatic CNS metastasis(mets)
in 6, skeletal events in 2, and patient refusal in 1, whilst in C group only one
(3%) of 40 failed to receive subsequent E therapy because of relapse
(carcinomatous lymphangitis) (�2-test; p � .001). Also, at the time of
relapse to the 1-st line therapy, PS deteriorated more frequently in E group
(8/23 vs. 7/40; p � .042) and, relapse with symptomatic CNS mets
seemed frequently observed in E group (6/23 vs. 4/40; p � .093).
Multivariate analysis revealed type of regimens undergone in the 1st-line
setting (E vs. C) correlated with failure of administration of subsequent
crossover therapy (odd ratio: 3.224, 95%CI: .1.032 – 5,417, p � .004).
Conclusions: It seems that pts with EGFR-mt tumors who were treated with
1st-line C had better opportunity to receive post-progression E therapy than
those treated with 1st-line E had chance to receive subsequent C therapy,
possibly due to difference in PS deterioration rate and relapse pattern.
7578 General Poster Session (Board #49D), Sat, 1:15 PM-5:15 PM
KIF5B-RET: Discovery of a novel fusion oncogene in lung adenocarcinomas
by a systematic screen for tyrosine kinase fusions and identification of
patients for a RET targeted therapy trial. Presenting Author: Yoshiyuki
Suehara, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: The mutually exclusive pattern of major targetable driver
oncogenes in lung adenocarcinomas (ADC) suggests that other similar
driver oncogenes may exist. We therefore performed a systematic screen for
tyrosine kinase (TK) fusions in cases without known driver oncogenes by
measuring aberrantly high RNA expression of kinase domain (KD) exons
relative to more 5’ exons. Methods: We studied 74 patients whose lung ADC
lacked mutations in KRAS, EGFR, BRAF, HER2, and ALK fusions. A
NanoString-based assay was designed to query the transcripts of 90 TKs at
two points: 5’ to the KD and within or 3’ to the KD. Tumor RNAs were
hybridized to the NanoString probes and analyzed for outlier 3’ to 5’
expression ratios. The assay was validated on samples with known ALK and
ROS fusions. Presumed novel fusion events were followed up by rapid
amplification of cDNA ends (RACE) and confirmatory RT-PCR. Results: The
NanoString assay identified aberrant 5’ to 3’ ratios in ROS and RET in 2
cases, respectively, out of 74. RACE analysis isolated a novel GOPC-ROS
fusion in the former and a novel KIF5B-RET fusion in the latter, both
confirmed by RT-PCR. Further screening by RT-PCR for KIF5B-RET
identified one more positive sample in the study set that had not been
detected by NanoString. At the RNA level, both fusions joined exon 15 of
KIF5B to exon 12 of RET, thus retaining a portion of the dimerization
domain of KIF5B and the entire KD of RET, analogous to RET fusions in
papillary thyroid carcinoma (TC). One KIF5B-RET patient was a 60 y.o.
female never smoker, the other, a 73 y.o. male former smoker. Conclusions:
The novel KIF5B-RET fusion described here and also recently reported by
Ju YS et al. (Genome Res, Dec 22, 2011) defines a new subset of lung ADC
with a potentially targetable driver oncogene. Based on these genetic data
and the preclinical activity of the RET inhibitor XL184 (Exelixis) in
papillary TC and its known activity in medullary TC with RET mutations, we
have initiated prospective testing for KIF5B-RET as part of our lung ADC
screening panel in anticipation of a planned phase 2 trial with XL184 in
patients with KIF5B-RET or related variant RET fusions.
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