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

494s Lung Cancer—Non-small Cell Metastatic
7557 General Poster Session (Board #46G), Sat, 1:15 PM-5:15 PM
Interim analysis of afatinib monotherapy in patients with metastatic
NSCLC progressing after chemotherapy and erlotinib/gefitinib (E/G) in a
trial of afatinib plus paclitaxel versus investigator’s choice chemotherapy
following progression on afatinib monotherapy. Presenting Author: Martin
H. Schuler, Department of Medical Oncology, West German Cancer Center,
University Duisburg-Essen, Essen, Germany
Background: The benefit of sustained ErbB family blockade in NSCLC
patients with acquired resistance (AR) to EGFR TKIs is unknown. We
investigated afatinib, an irreversible blocker of EGFR (ErbB1), HER2
(ErbB2) and ErbB4 receptor tyrosine kinases, in patients with metastatic
NSCLC, who had failed chemotherapy and E/G. Methods: This was a Phase
III, randomized, open-label, multi-center trial. Patients with pathologically
confirmed Stage IIIB/IV metastatic NSCLC after �1 line of chemotherapy
who failed E/G received oral afatinib 50 mg until disease progression (Part
A). After progression, patients with clinical benefit (�12 wks) were eligible
to continue afatinib 40 mg plus paclitaxel or receive investigator’s choice
chemotherapy (Part B). Primary endpoint for Part A was PFS (RECIST 1.1;
CT scan every 6 wks). Available tumor samples were collected for central
EGFR mutation testing; local mutation data were also collected. An interim
analysis of Part A, assessing afatinib monotherapy, is reported. Results:
Part A enrolled April 2010 through to May 2011; 1154 patients received
afatinib monotherapy. The majority had adenocarcinoma (85%), 57% were
female, 43% were Asian, 54% were never smokers. Best response to prior
E/G was CR (2%), PR (31%), SD (42%) and PD (20%). Median PFS for
afatinib was 3.3 mths; 88 patients (8%) achieved an objective tumor
response, 648 (56%) had SD. For EGFR mutation positive patients (n�49,
centrally confirmed), PFS was 4.2 vs. 2.6 mths for EGFR mutation negative
patients (n�35). When applying clinical enrichment criteria for AR, PFS
was 4.2 mths for those with enrichment (n�597) vs. 2.8 mths for those
without (n� 557; logrank test p�0.0001). The most common grade 3/4
adverse events were diarrhea (17%) and rash/acne (11%). In Part A, 99
patients remain on treatment. Conclusions: Afatinib monotherapy provided
a clinically meaningful benefit in this large, treatment-refractory NSCLC
trial, similar to LUX-Lung 1. Those clinically enriched for AR to EGFR TKIs
achieved prolonged disease control upon continued ErbB blockade.
7559 General Poster Session (Board #47A), Sat, 1:15 PM-5:15 PM
Final overall survival and updated biomarker analysis results from the
randomized phase III ICOGEN trial. Presenting Author: Yan Sun, Cancer
Hospital, Chinese Academy of Medical Sciences, Beijing, China
Background: A total of 399 pretreated patients with advanced NSCLC were
randomly assigned to receive gefitinib or icotinib in the phase III ICOGEN
trial, the first head-to-head phase III trial of EGFR-TKIs. The results of the
primary endpoint, PFS, have been reported previously. This report represents
the final OS and biomarker analysis results. Methods: EGFR mutation
was evaluated by using Scorpion ARMS (QIAGEN, n�152). Overall survival
was analyzed by Cox proportional-hazards model analysis at 82% maturity.
Results: Median OS was 13.3 months for icotinib and 13.9 months for
gefitinib (hazard ratio [HR] � 0.90; 95% CI, 0.79 to 1.02; P � .109). The
EGFR mutation rate was 43% in the icotinib group and 59% in the gefitinib
group. Compared to wild type patients, patients with EGFR mutation had
longer PFS (median, 6.2m vs. 2.3m; P�.00001) as well as OS (median,
20.5m vs. 7.7m; P�.00001). There were no significant differences in PFS
or OS between the two treatment groups in EGFR mutation-positive
subgroup (median PFS, 7.8m vs. 5.3m for icotinib and gefitinib, respectively,
P �.3162; median OS, 20.9m vs. 20.2m for icotinib and gefitinib,
respectively, P �.7611.) or in EGFR mutation-negative subgroup (median
PFS, 2.3m vs. 2.2m for icotinib and gefitinib, respectively, P �.1531;
median OS, 7.8m vs. 6.9m for icotinib and gefitinib, respectively, P
�.7885.). Conclusions: There is no statistically significant difference
between icotinib and gefitinib in PFS or OS when given to NSCLC patients.
This suggests that icotinib can provide similar OS benefits to gefitinib in
advanced NSCLC patients. Moreover, EGFR mutation status is the strongest
predictor in identifying which patients are most likely to benefit from
icotinib.
7558 General Poster Session (Board #46H), Sat, 1:15 PM-5:15 PM
Afatinib monotherapy in patients with metastatic squamous cell carcinoma
of the lung progressing after erlotinib/gefitinib (E/G) and chemotherapy:
Interim subset analysis from a phase III trial. Presenting Author: Joo-Hang
Kim, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul,
South Korea
Background: Patients with squamous NSCLC have limited treatment options.
For those deriving benefit from EGFR TKIs, it is unclear whether
sustained ErbB family blockade offers benefit upon progression. We
evaluated afatinib, an irreversible blocker of EGFR (ErbB1), HER2 (ErbB2)
and ErbB4 receptor tyrosine kinases, in patients with metastatic NSCLC
who had failed chemotherapy and E/G. Here we describe a pre-specified
analysis of those with squamous histology in Part A. Methods: This
randomized Phase III, open-label, multi-center trial enrolled patients with
pathologically confirmed metastatic NSCLC after failing �1 line of cytotoxic
chemotherapy and E/G. In Part A, patients received oral afatinib 50
mg until disease progression. Those with clinical benefit (�12 wks) who
progressed were eligible to receive afatinib plus paclitaxel or investigator’s
choice chemotherapy (Part B). Primary endpoint was PFS (RECIST 1.1).
Following an amendment, an interim analysis of Part A was performed to
assess afatinib monotherapy. Results: Patient enrolment into Part A was
from April 2010 to May 2011. Of 1154 afatinib-treated patients, 91 (8%)
had squamous histology; 18/91 and 40/91 had CR/PR and SD on prior E/G,
respectively (by investigator). Median age was 63 yrs, 71% were male, 76%
were current/ex-smokers. Median PFS on afatinib was 3.7 mths in the
squamous histology subset. Of 91 patients, 42 had PFS �3 mths; 13 had
PFS of �6 mths. In evaluable patients (n�77), 1 CR and 3 PRs were
confirmed; 51 and 22 patients had best overall response of SD and PD,
respectively. Of the 31 patients with PD on prior E/G with no intervening
chemotherapy, 10 achieved confirmed disease control (2 PR; 8 SD) on
afatinib. Most commonly reported grade 3/4 adverse events (AEs) in Part A
were diarrhea (13%) and rash/acne (12%). The safety profile in the
squamous histology subset was similar to that observed for the whole trial.
Conclusions: Afatinib monotherapy demonstrated encouraging activity in
treatment-refractory NSCLC patients with squamous histology that merits
further evaluation.
7560 General Poster Session (Board #47B), Sat, 1:15 PM-5:15 PM
A randomized phase III study of a cisplatin (CDDP) and docetaxel (DOC)
with or without irinotecan (CPT) in pts with advanced NSCLC: Okayama
Lung Cancer Study Group OLCSG 0403 trial. Presenting Author: Toshiaki
Okada, Chugoku Central Hospital, Fukuyama, Japan
Background: CDDP-based doublet chemotherapy provides a significant but
modest survival prolongation in untreated advanced NSCLC with MST of
around 12 months. Based on the favorable efficacy profile in our previous
phase II trial of triplet chemotherapy with CDDP, DOC, and CPT (response
rate: 57.1%, MST: 17 months) (JTO 2007), we conducted a phase III study
to compare this regimen with CDDP and DOC doublet therapy in the
first-line setting. Methods: Pts were randomly allocated to the triplet
therapy (A arm; CDDP 60 mg/m2 , day 1; DOC 60 mg/m2 , day 1; and CPT 60
mg/m2 , day 2; q3 wks, determined based on our phase I study result) or a
standard doublet chemotherapy (B arm; CDDP 80 mg/m2 , and DOC 60
mg/m2 , day 1; q3 wks). The primary endpoint was OS whilst secondary
endpoints included response rates, PFS, and toxicity. Results: Between
2004 and 2009, 120 pts were enrolled (A/B: 60 pts each). Objective
response was comparable between the arms (18 pts [30%] each, p �
0.571). As for toxicity, grade 3-4 neutropenia, principal toxicity, was
observed in 93% vs. 58% (p � 0.001). Although grade 3 febrile
neutropenia was observed in 53% and 18% of the pts (p � 0.001), none of
whom further developed toxic deaths. At a median follow-up time of 64.2
months, median PFS time and 1-year PFS rate were 5.3 vs. 4.3 months and
13.3% vs. 11.7%, respectively (stratified logrank test; p � 0.872). There
was also no difference in OS (MST, 16.8 vs. 12.2 months; 1-year OS rate,
68.0% vs. 53.0%; stratified logrank test; p � 0.846). Subgroup analysis
for OS showed that never smokers (HR � 0.366; 95% CI � 0.072-1.866)
tended to benefit from the triplet chemotherapy compared with eversmokers
(HR � 1.380; 95% CI � 0.771-2.473) despite no statistical
significance (p for interaction � 0.150). Similar trend in interaction
between treatment effect and smoking status was also observed in PFS.
Conclusions: This triplet chemotherapy failed to produce a significant
antitumor activity as compared with the standard doublet therapy.
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