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

474s Lung Cancer—Non-small Cell Local-Regional/Small Cell/Other Thoracic Cancers
7092 General Poster Session (Board #41C), Sat, 1:15 PM-5:15 PM
Circulating tumor cells (CTCs) in patients (pts) with small cell lung cancer
(SCLC) as a marker of disease burden and therapeutic response, and
predictor of disease relapse. Presenting Author: Anjana Ranganathan,
University of Pennsylvania, Philadelphia, PA
Background: Currently there are no validated biomarkers for assessment or
prediction of disease burden or activity in SCLC. Enumeration of CTCs by
CellSearch is FDA approved, highly reproducible and validated in other
malignancies. Application as a prognostic and predictive marker in SCLC is
limited due to a lack of studies documenting serial monitoring in pts on
therapy. Methods: We are conducting a prospective study serially enumerating
CTCs in pts with newly diagnosed SCLC. CTC number (per 7.5 ml
peripheral blood) and percentage of CTCs demonstrating DNA damage and
apoptosis based on �H2AX and M30 staining respectively, are being
assessed prior to initiation of chemotherapy, during each cycle and at
relapse. We are correlating CTC number with disease stage, number of
metastatic sites, response to therapy, and time to progression (TTP).
Results: 21 SCLC pts are evaluable. 9 pts with limited disease (LD) had
median baseline CTC value of 1 (0-8); only 2 of 9 pts had �5 CTCs. 12 pts
with extensive disease (ED) had median baseline CTC value of 80.5
(0-37780); 8 of 12 pts had �5 detectable CTCs (p value 0.02). Amongst
the 12 pts with ED, median baseline CTC count was higher in pts with �3
(n�3) compared to 1-2 sites of metastatic disease (n�9) (2668 vs 71; p
value 0.52). Median percentage of CTCs positive for �H2AX and M30 was
also higher for pts with �3 compared to 1-2 metastatic sites (83, 164.5 vs.
2, 7.5) (p-value 0.40, 0.69). Serial CTC data are available on 3 pts with
ED; all had responsive disease and reduction in CTC number to 0-1 after 2
cycles of chemotherapy. As this protocol is ongoing, correlation of CTCs
with updated response status and TTP will be presented at the ASCO
meeting. Conclusions: CTCs can be isolated and serially enumerated in pts
with SCLC. Baseline CTCs correlate directly with disease stage. In pts with
� 3 metastatic sites, baseline CTCs tend to be greater and show higher
levels of DNA damage and apoptosis compared to those with 1-2 metastatic
sites. Reduction in CTCs is associated with radiographic response to
therapy. Correlation between absolute number at baseline and TTP is not
yet known.
7094 General Poster Session (Board #41E), Sat, 1:15 PM-5:15 PM
A phase II study of second-line bendamustine in relapsed or refractory
small cell lung cancer (SCLC). Presenting Author: Christine Marie Lovly,
Vanderbilt Ingram Cancer Center, Nashville, TN
Background: Bendamustine is an alkylating agent with a nitrogen mustard
group and purine-like benzimidazole group. Bendamustine in combination
with carboplatin has shown efficacy as first line therapy in extensive stage
SCLC with RR 73%, TTP 5.2 months and OS 8.3 months [Köster, et al, JCO
2007]. This study aims to investigate the efficacy and safety of single agent
bendamustine as 2nd or 3rd line therapy in patients with extensive-stage
disease, small-cell lung cancer (ED-SCLC). Methods: This is an open-label,
single-arm, multicenter phase II trial. Eligible patients had previously
treated ED-SCLC, up to 2 prior regimens, ECOG performance status 0-2,
evaluable/measurable disease, and adequate marrow, renal and hepatic
function. Patients with stable treated brain metastases were allowed.
Patients were treated with bendamustine (120mg/m2 IV days 1 and 2 every
3 weeks) for up to 6 cycles. Evaluation occurred every 2 cycles. Primary
endpoint was TTP; secondary endpoints include RR, PFS, OS, and toxicity.
Results: 48 patients were enrolled; 56% were male and 96% were
Caucasian. 33 patients were evaluable for response. There was 1 CR, 9 PR,
13 SD (48% disease control rate) and 10 PD. Median TTP was 3.37
months (95% CI 2.30 to 4.47 months). At the time of analysis, 13 patients
were alive and with a median overall survival of 4.77 months (95% CI 3.67
to 6.07 months). 5 patients (10.4%) required dose reductions due to AEs,
2 due to fatigue, 1 due to neutropenia, 1 due to pancytopenia and 1 due to
pneumonia. Grade 3/4 AEs included fatigue (18.8%), dyspnea (14.5%),
infection without neutropenia (12.5%), anemia (8.3%), neutropenia (8.3%),
and diarrhea (8.3%). Conclusions: These data indicate that single agent
bendamustine appears to be well tolerated and effective in the second or
third line setting for patients with SCLC.
7093 General Poster Session (Board #41D), Sat, 1:15 PM-5:15 PM
NCIC IND.190: A phase I trial of MK-0646 in combination with cisplatin
and etoposide in extensive-stage small cell lung cancer (ES SCLC).
Presenting Author: Peter Michael Ellis, Juravinski Cancer Centre, Hamilton,
ON, Canada
Background: Increased serum levels of insulin like growth factor (IGF), plus
overexpression of the IGF-receptor (IGFR) are implicated in SCLC cell
growth and proliferation, making suppression of the IGFR a potential
therapeutic target. MK-0646 is a monoclonal antibody directed against the
IGFR. The aim of this study was to determine the recommended phase II
dose (RP2D) of cisplatin, etoposide plus MK-0646. Methods: We conducted
a phase I study of two dose levels of MK-0646 (DL1 5mg/kg, DL2
10mg/kg IV weekly) in combination with cisplatin (25mg/m2 ) and etoposide
(100mg/m2 ) IV D1-3, q21d, for patients with chemotherapy-naive ES
SCLC, PS 0-2. Patients with treated stable brain metastases were eligible.
Patients completing 4-6 cycles of combination therapy could continue
single agent MK-0646 until disease progression. Primary outcome was
determination of the RP2D. Secondary outcomes included ORR (RECIST
1.1), and toxicity (CTCAEv3). Results: A total of 12 patients were treated
(DL1 – 3, DL2 – 9). The median age was 63 years (48-70), with 6 males
and 6 females. Most subjects were good ECOG PS (PS1–8,PS2–4)and
had 4 or more sites of disease (n�8). No DLTs were observed in DL1 or
DL2. In an expanded DL2 cohort, 1 patient died from neutropenic sepsis
during cycle 1. The median number of treatment cycles of chemotherapy
was 4 (DL1) or 5 (DL2) and MK-0646 was 6 (DL1&2). Dose delays were
observed for chemotherapy (DL1 - 2, DL2 – 6) and MK-0646 (DL1 – 3, DL2
– 7). The confirmed ORR was 72.7% (PR 8, SD 2, PD 1, non-evaluable 1).
Grade �3 toxicities (any cycle) occurring in more than 1 patient included:
neutropenia (92%); thrombocytopenia (25%); leukopenia (50%); anemia
(17%); fatigue (33%); joint pain (17%); thrombosis (25%). Grade 2 or 3
hyperglycemia was observed in 1 of 3 (DL1) and 5 of 9 (DL2). Eight SAEs
were observed in 3 patients (thrombosis, febrile neutropenia, infection,
syncope, fatigue 2, dyspnea, back pain). Conclusions: MK-0646 can be
combined at full dose with standard doses of cisplatin and etoposide
(25mg/m2 and 100mg/m2 D1-3) with a RP2D of MK-0646 10mg/kg/week.
The observed toxicities are consistent with that expected from cisplatin and
etoposide except for hyperglycemia, which appears dose dependent.
7095 General Poster Session (Board #41F), Sat, 1:15 PM-5:15 PM
ABEL trial: A phase II randomized trial adding bemiparin (B) to chemoradiotherapy
(CT-RT) in limited-stage small cell lung cancer (SCLC)—Final
results. Presenting Author: Bartomeu Massuti, Alicante University Hospital,
Alicante, Spain
Background: Low molecular weight heparins (LMWH) could improve therapeutic
outcomes in patients with advanced cancer. Heparin binding growth
associated molecule is a member of growth factors involved in proliferation,
angiogenesis and metastases in SCLC. LMWH associated with CT increase
survival in cancer patients (Cochrane DB Systematic Reviews 2011).
LMWH do not increase hemorrhagic events when used in neoplastic
patients. Methods: Open randomized phase II multicentric trial to assess
efficacy and safety of adding bemiparin to standard CT-RT in patients with
SCLC with limited disease. CT: Cis/carboplatin � etoposide x 4-6 cycles.
Concurrent early thoracic RT (45-50 Gy) and prophylactic cranial irradiation
in case of response. Patients (p) were randomly allocated to addition of
B at daily subcutaneous dose of 3.500 UI during 26 weeks. Primary
end-point: progression free survival (PFS). Secondary end-points: response
(RECIST), safety profile (CTC), venours thromboembolic (VTE) and hemorrhagic
events incidence and overall survival (OS). Sample size 130 p.
Preplanned interim analysis after inclusion 30 p. Results: From October-05
to January/10 39 p were included. Study was closed after interim analysis
due to poor recruitment. 38 evaluable p. ITT analysis: 20 CR-RT � Bvs18
CT-RT. No significant disbalance in patient characteristics and prognostic
factors. Median PFS 58.6 weeks (CT-RT�B) vs 38.8 w (CT-RT) (HR 2.576;
Log-rank p�0,018). RR: 65% (CT-RT�B) vs 55% (CT-RT) (NS); Median
OS 161.8 w (CT-RT�B) vs 49.3 w (CT-RT) (HR 2.96; Log-rank p�0,012).
2-year survival rate: 68.6% (CT-RT�B) vs 29.4% (CT-RT) (p�0,0042).
Safety: G3-4 AE: 50% vs 67%; bleeding events: 10% vs 27% (NS);
thrombocytopenia 15% vs 50% (p�0.024); VTE: 0 vs 22% (p�0.041).
Conclusions: Addition of B (3.500 u/daily s.c. during 26 w) to CT-RT in
SCLC with LD significantly increases PFS and OS. B does not increase
hemorragic events and significantly reduces VTE. In spite of early closure of
the trial due to poor accrual, these results warrants further research in this
approach trying to improve current outcomes of SCLC. ClinicalTrials.gov Id:
NCT00324558.
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