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

Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7080 General Poster Session (Board #39G), Sat, 1:15 PM-5:15 PM
Circulating tumor cell (CTC) as a significant clinical marker in epithelioidtype
malignant pleural mesothelioma (MPM). Presenting Author: Kazue
Yoneda, Hyogo College of Medicine, Nishinomiya, Japan
Background: Circulating tumor cell (CTC) is a surrogate of distant metastasis,
and our preliminary study suggested that CTC detected by an
EpCAM-based immuno-magnetic separation system (“CellSearch”) was a
useful clinical marker in the diagnosis of malignant pleural mesothelioma
(MPM) (Tanaka F. et al ASCO 2008). Methods: Patients who presented at
our institute to receive pleural biopsy with suspicion of MPM were
prospectively enrolled. CTCs in 7.5mL of peripheral blood were quantitatively
evaluated with the CellSearch system. Results: Among 136 eligible
patients, 104 were finally diagnosed with MPM, and 32 were with
non-malignant diseases (NM). CTC was positive (CTC�1) in 32.7%
(37/104) of MPM pts, and in 9.4% (3/32) of NM pts (p�0.011).
CTC-count was significantly higher in MPM (range, 0-9) than in NM (range,
0-1; p�0.007). According to a ROC curve analysis, the CTC-test provided a
significant diagnostic performance in discrimination between MPM and
NM (AUC� 0.623; P�0.036). Among MPM pts, CTC-positivity and
CTC-count were significantly increased with tumor progression (p�0.026
and p�0.008, respectively). For all MPM pts, there was no significant
difference in overall survival between CTC-positive and negative pts.
However, in a planned subset analysis, CTC was a significant factor to
predict poor prognosis (median survival time, 8.0 months for CTC-positive
pts, and 20.3 months for negative pts; p�0.012) in pts with epithelioidtype
MPM in which CTC was exclusively positive; a multivariate analysis
confirmed that CTC, along with PS, was an independent prognostic factor
(HR�2.38; P�0.006). Conclusions: CTC was a significant diagnostic
marker in discrimination between MPM and NM. CTC-positivity was a
significant and independent prognostic factor to predict a poor prognosis of
epithelioid MPM.
Epithelioid Non-epithelioid
No. of pts 79 25
CTC-positive pts 32 (40.5%) 2 (8.0%)
OS (median) 8.0m (CTC�1) vs. 20.3m 3.3m (CTC�1) vs. 5.7m
(CTC�0)
(CTC�0)
(p�0.012)
(p�0.482)
7082 General Poster Session (Board #40A), Sat, 1:15 PM-5:15 PM
Malignant pleural mesothelioma (MPM) in elderly patients: A multicenter
survey. Presenting Author: Federica Grosso, Oncology SS Antonio e Biagio
General Hospital, Alessandria, Italy
Background: The incidence of malignant pleural mesothelioma (MPM) in
elderly patients (pts) is increasing in Western countries. Elderly pts with
MPM are under-represented in clinical trials, and there are no specific
guidelines for their management. The aim of this study was to perform a
retrospective survey on this patient population in four Oncology Departments
with high MPM accrual and expertise. Methods: The clinical records
of elderly pts (�70 years old) with MPM referred to the participating
centers from January 2005 to November 2011 were reviewed. For each
patient, age and gender, histology, Eastern Cooperative Oncology Group
Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and
treatment modalities were collected. The study endpoint was overall
survival (OS). Results: Out of a total of 610 cases, 210 elderly pts were
identified (34% of the whole MPM population observed in the study
period). Pts characteristics were: median age 75 yrs (range 70-92), M/F
132/78, epithelial/non-epithelial histology 140/70, ECOG-PS 0/1/2/
unknown 130/67/9/4. CCI was 0 in 128 pts (61%), �4 in 59 pts (28%).
Treatment was multimodality therapy including surgery in 16, chemotherapy
in 153 (73%) and best supportive care only in 41 pts (19%).
Chemotherapy was mainly pemetrexed-based. Median OS was 11.3 months.
Non-epithelial histology, age �75 yrs and the presence of comorbidities
(CCI �1, p�.003; CCI �4, p�0.0001) were significantly correlated to a
shorter OS. Conclusions: Pemetrexed-based chemotherapy is feasible in
selected elderly pts with MPM. Comorbidity is a significant prognostic
factor, and should be carefully considered in patient selection. Prospective
dedicated trials in elderly pts with MPM selected according to comorbidity
scales are warranted.
471s
7081 General Poster Session (Board #39H), Sat, 1:15 PM-5:15 PM
Phase II study of bortezomib with cisplatin as first-line treatment of
malignant pleural mesothelioma (MPM): EORTC 08052. Presenting Author:
Mary O’Brien, The Royal Marsden Hospital, Sutton, United Kingdom
Background: Cisplatin is one of the most active drugs available in MPM
while bortezomib has shown some activity in single agent phase II studies
against MPM. This was a prospective phase II study of cisplatin and
bortezomib (CB) in the first line treatment of MPM. Methods: Patients with
histological proven MPM, with performance status (PS) 0/1, were eligible.
The doses were cisplatin 75mg/m2 /3 wks and bortezomib 1.3mg/m2 day 1,
4, 8, 11 every 3 wks. The primary end-point was progression free survival
rate at 18 wks (PFSR�18). The 2-stage Simon design (a�0.1; b � 0.05,
P0�0.50 and P1�0.675) was used. In the first step of the study 37 eligible
patients were planned. If more than 19 patients were alive and free of
progression at 18 wks the total sample size was increased to 76 eligible
patients. Results: Between 2007 and 2010 82 patients were entered. The
median follow-up time is 32.3 months The median age was 55 years
(range: 22-77yrs), male/female: 55/27 , PS 0/1: 9/73, Stage T1: 10%; T2:
42%, T3: 25%; T4: 23% and N0: 57%; N1: 4%; N2: 33%; N3: 6%. The
median number of cycles received was 4 and 38% received 6 cycles.
Cisplatin/ bortezomib dose intensity was 98/ 80%. Toxicity (grade 3/4):
neutropenia 10%, thrombocytopenia 11%, anaemia 1%. Grade 3-4
hyponatraemia/ hypokalaemia occurred in 46/ and 17%. Grade 2 tinnitus,
grade 3 fatigue occurred in 16%, and 12%, of patients. Motor/sensory/
other neurotoxicity was grade 1: 6/28/7%, grade 2: 2/26/2% and grade 3:
1/7/2% respectively. There were 2 toxic deaths at 32 and 74 days due to
acute pneumonitis and cardiac arrest. The PFRS-18 (including symptomatic
progression) was 53% (80% confidence intervals, CI, 42-64%). The
overall survival was 13.5 months (95% CI 10.5-15) with 56% (95% CI
44-66%) alive at 1 year. The PFS was 5.1 months (95% CI 3.3-6.5).
Conclusions: On the basis of the PFRS-18, the null hypothesis could not be
rejected, although CB gave predictable toxicity and was as active as other
reported regimens in MPM.
7083 General Poster Session (Board #40B), Sat, 1:15 PM-5:15 PM
SWOG 0722: A phase II study of mTOR inhibitor everolimus (RAD001) in
malignant pleural mesothelioma (MPM). Presenting Author: Linda L.
Garland, Arizona Cancer Center, Tucson, AZ
Background: MPM preclinical studies demonstrate activation of AKT
pathway proteins, including mTOR, and provide the rationale to test
everolimus, an mTOR inhibitor, in MPM. Methods: Unresectable MPM
patients (pts) after 1-2 systemic regimens (including a platinum-based
regimen), with PS 0-1, measurable disease and adequate organ function
were treated with daily oral everolimus 10 mg. Study endpoints were
progression-free survival (PFS) at 4 months, response rate,overall survival
(OS), and frequency/severity of toxicities. Results: 61 pts were registered
between 12/2008 and 9/2011; there were 57 evaluable pts for the primary
endpoint of 4-month PFS. Median age was 65.9 yrs; M/F 43/14; prior
regimens (1/2: 58%/42%); PS 0/1 (21%/79%); epithelial subtype 61%;
biphasic 7%; NOS 28%; pending 4%. 5 pts remain on treatment.
Preliminary data for 35 of 57 pts are as follows: RR 0% by standard RECIST
and DCR of 14/35 (40%); data by mod RECIST are not yet available.
Estimated 4-month PFS was 34% with an estimated median PFS of 3
months. The null hypothesis of 4-month PFS � 30% could not be rejected
(p�0.28). 41 pts have died; median OS is estimated at 5 months. Frequent
grade 1-3 toxicities were fatigue (55.4%), hypertriglyceridemia (41.1%),
anemia (39.3%), nausea (33.9%), oral mucositis (32.1%), anorexia
(32.1%), diarrhea (26.8%), and hyperglycemia (26.8%). One pt each had
grade 4 and grade 5 dyspnea. Conclusions: The trial did not achieve the
primary endpoint of an improvement of PFS at 4 months from 30% to 50%.
Inhibition of mTOR using single agent everolimus is not active in unselected
MPM patients. Other strategies for targeting the activated AKT
pathway in MPM remain of interest.
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