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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7012 Poster Discussion Session (Board #4), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Feasibility trial of adjuvant chemotherapy with docetaxel (DOC) plus
cisplatin (CDDP) followed by maintenance chemotherapy of S-1 in completely
resected non-small cell lung cancer (NSCLC): Thoracic Oncology
Research Group (TORG) 0809. Presenting Author: Seiji Niho, Division of
Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba,
Japan
Background: Maintenance chemotherapy could prolong overall and/or
progression-free survival in advanced NSCLC. S-1 is an oral anticancer
agent comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium
oxonate. The TORG 0809 study was conducted to evaluate the
feasibility and efficacy of maintenance chemotherapy of S-1 following
DOC�CDDP in patients (pts) with curatively resected stage II and IIIA
NSCLC. Methods: Pts received 3 cycles of DOC (60mg/m2 d1) plus CDDP
(80mg/m2 d1), q3-4w, and subsequently S-1 at 40mg/m2 twice a day for
14 consecutive days, q3w, for more than 6 months (max 1 year). The
primary endpoint was determination of feasibility, which was defined as the
proportion of pts who had completed maintenance for 8 cycles of S-1 or
more. If the lower confidence interval (CI) of this proportion was 50% or
more, the feasibility of the treatment was considered confirmed. The
sample size was set to be 125. Results: Between Jun 2009 and Nov 2010,
131 pts were enrolled, of whom 129 pts were eligible and assessable. The
median age was 63 (23-74 years); PS 0: 107, 1: 22; p-stage IIA: 19, IIB:
30, IIIA: 80; adenocarcinoma: 99, non-adenocarcinoma: 30. Of 129 pts,
109 pts (84.5%) completed 3 cycles of DOC�CDDP. 106 pts initiated the
maintenance S-1 and 66 pts (51.2%, 95% CI: 42.5-59.8) completed 8
cycles or more S-1 treatment; this percentage was less than our previously
defined criterion for treatment feasibility, since 32 pts terminated maintenance
S-1 at 3 cycles or less. Grade 3/4 toxicities during the maintenance
S-1 included anemia (7.3%), neutropenia (3.7%), anorexia (3.7%),
dyspnea (1.8%), infection with neutropenia of grade 0 to 2 (1.8%). Febrile
neutropenia was not observed. One pt developed interstitial pneumonia and
sepsis, resulting in treatment-related death. Recurrence-free survival data
will be presented. Conclusions: The toxicity level was acceptable, although
the results did not meet our criterion for feasibility. Modification of the
treatment schedule of maintenance S-1, such as a 2-week rest period
rather than 1-week, might improve treatment compliance.
7014 Poster Discussion Session (Board #6), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Quantitating pathologic response to neoadjuvant chemotherapy in KRASmutated
versus nonmutated lung cancers. Presenting Author: Jamie E.
Chaft, Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Trials of neoadjuvant chemotherapy in non-small cell lung
cancers (NSCLC) have demonstrated that pathologic response correlates
with downstaging and survival. There is controversy as to whether KRAS
mutated patients (pts) have the same benefit with adjuvant chemotherapy
as non-mutated pts however the impact of KRAS mutations on response to
neoadjuvant therapy has not been reported. Methods: Pts with resectable
stage I-III non-squamous NSCLCs were treated with 4 cycles of cisplatin,
docetaxel, and bevacizumab, followed by surgical resection. Tumors were
tested for KRAS mutations. Percent treatment effect (necrosis, inflammation,
fibrosis) was quantified histologically. Pts were followed until disease
recurrence and/or death. Binary variables were compared using the Fisher’s
Exact Test. Survival was assessed by pathological response based on the
literature (�90 vs �90%) using the Kaplan-Meier method, stratified by
stage (IB-IIB vs. III) and by KRAS mutation. Results: We accrued 51 pts.
34/51 (67%) had clinical stage IIIA disease. 48 had molecular testing:
14/48 (29%) had KRAS mutations and 4/48 (8%) had EGFR mutations.
The median follow-up was 2 years (yr) (range, 3-63 months). 41 pts had
resection and analysis for pathological response. The 2 yr disease free
survival (DFS) and overall survival (OS) were superior in the 11/41 (27%)
with �90% versus those with �90% treatment effect: DFS 91% vs. 56%,
p�0.029 and OS 100% vs. 60%, p�0.013. These outcomes remained
significant when adjusted for stage. For pts with KRAS mutations, 0 of 10
tumors analyzed had �90% treatment effect whereas 11 of 31 (35%) pts
with wild-type KRAS had �90%, p�0.039. There was an inferior median
OS for KRAS mutated pts (22 months) compared to pts without a known
KRAS mutation, (Not Reached, p�0.03). Conclusions: Following neoadjuvant
chemotherapy, pts with tumors having �90% necrosis had improved
survival. There were no patients with KRAS mutation that achieved �90%
treatment effect in response to cisplatin, docetaxel, and bevacizumab.
Adaptive adjuvant trial strategies to improve upon outcomes of those with
�90% necrosis at resection and new approaches specifically targeting
KRAS-mutated NSCLCs are needed.
7013 Poster Discussion Session (Board #5), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
MAGE-A3 cancer immunotherapeutic in resected stage IB-III NSCLC
patients with or without sequential or concurrent chemotherapy. Presenting
Author: Jean-Louis Pujol, CHU - Maladies Respiratoires, Montpellier,
France
Background: Previous trials with the MAGE-A3 recombinant (rec) protein
formulated with an immunostimulant have shown induction of specific
immune responses and signals of clinical activity in different cancer
diseases. In this phase I/II study (NCT 00455572), we evaluated the safety
profile of the MAGE-A3 cancer immunotherapeutic (CI), formulated with
the rec MAGE-A3 protein and the AS15 immunostimulant, and the
induction of specific immune response with or without adjuvant chemotherapy
(CT). Methods: MAGE-A3 CI was administered i.m. 8q3w in
resected MAGE-A3� stage IB-III NSCLC patients (pts). Three cohorts (C)
were evaluated: Immunization with concurrent cisplatin plus vinorelbine
(C1), sequentially after the same CT (C2) or with no CT (C3). The
anti-MAGE-A3 humoral and cellular immune responses were evaluated by
ELISA and intracellular cytokine staining (T cells producing both IFNg and
TNF) respectively. Adverse Events (AEs) were graded according to CTCAE v.
3.0. Results: A total of 38/55 treated pts received the 8 doses schedule
(15/19 in C1, 14/18 in C2, 9/18 in C3). Almost all pts reported at least one
AE, mostly general constitutional disorders and administration site reactions.
Six patients reported related grade 3 AEs. No related grade 4-5 AE or
related SAE were reported. Immunogenicity results in the total treated
population are reported in the table below. Conclusions: In this trial,
patients in cohorts 2 and 3 correspond to the two populations enrolled in
the Phase III MAGRIT trial evaluating the same MAGE-A3 CI. The phase I/II
results suggest that this CI is well tolerated and induces in all treated pts
specific antibodies against MAGE-A3 after 4 doses in presence or not of
concurrent or sequential adjuvant CT. About 25% of the treated pts are
considered as CD4 responders in presence or not of concurrent or
sequential adjuvant CT.
C1
n/N
C2
n/N
455s
C3
n/N
Cohort
Seropositivity*
-
-
-
After 4 doses
15/15
15/15
12/12
After 8 doses
15/15
13/13
9/9
CD4 response** 4/11 4/15 2/8
CD8 response** 1/11 1/15 0/8
n: number of seropositive/responding patients; N: Total number of pts with
available samples; *: Anti-MAGE-A3-Antibodies; **: Responders are pts with a
response ratio baseline/any timepoint ��4 folds.
7017 Poster Discussion Session (Board #9), Sun, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Updated results of a phase III trial comparing standard thoracic radiotherapy
(RT) with or without concurrent daily low-dose carboplatin in
elderly patients (pts) with locally advanced non-small cell lung cancer
(NSCLC): JCOG0301. Presenting Author: Hiroaki Okamoto, Yokohama
Municipal Citizen’s Hospital, Yokohama, Japan
Background: We previously reported the superiority of combined chemoradiotherapy
(CRT) over RT alone in elderly pts with locally advanced
NSCLC (Atagi et al. ECCO2011). One and a half years follow-up data from
last accrual are presented. Methods: Pts older than 70 years with unresectable
stage III NSCLC were randomized to either RT alone (RT arm), a total
dose of 60 Gy, or CRT arm including the same RT plus concurrent
chemotherapy with carboplatin 30 mg/m2 /day, 5 days/week � 20 days. The
primary endpoint was overall survival (OS). The planned sample size was
100 pts in each arm with one-sided alpha of 5% and 80% power to detect a
difference in median survival time (MST) from 10 months in RT arm to 15
months in CRT arm. Results: Between Sep 2003 and May 2010, 200 pts
were randomized. Baseline characteristics were similar in the RT (n�100)
vs CRT (n�100) arms: median age, 77 vs 77 years; stage IIIB (n), 46 vs
49; PS 0/1/2 (n), 41/55/4 vs 41/56/3. The second planned interim analysis
was performed 10 months after the completion of accrual. In accordance
with the pre-specified stopping rule, the JCOG Data and Safety Monitoring
Committee recommended early publication of this trial because of the
difference in OS favoring the CRT arm. In the updated analysis, OS was
better in the CRT arm than the RT arm (HR � .64, 95% CI � .46-.89,
one-sided p � .0033 by stratified log-rank test). In each arm (RT/CRT),
MST was 16.5 mo/22.4 mo with 3-year OS of 14.3%/34.6%, response rate
of 44.9%/54.6% (p�.201) and median progression-free survival of 6.9
mo/8.9 mo (p�.003). Gr 3/4 toxicities were (RT/CRT): neutropenia
0%/57.3%, infection 4.1%/12.5%, dysphagia 0%/1.0%, late RT toxicities
7.4%/7.5%. The pattern of relapse site and post-protocol treatment were
almost similar between the arms. Even after an adjustment by the Cox
regression analysis with six variables [stage, PS, sex, age, histology,
smoking status], CRT arm showed better survival (HR�.71, p�.038).
Conclusions: The CRT using daily carboplatin is considered to be the
standard treatment for elderly pts with locally advanced NSCLC.
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