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

5544 General Poster Session (Board #22D), Sat, 1:15 PM-5:15 PM
A multi-institutional phase II trial of pazopanib monotherapy in advanced
anaplastic thyroid cancer. Presenting Author: Keith Christopher Bible,
Mayo Clinic, Rochester, MN
Background: Pazopanib, an orally bioavailable multitargeted inhibitor of
kinases including VEGF-R, demonstrated impressive activity in metastatic
differentiated thyroid cancer (49% durable RECIST PRs) and promising
preclinical activity in anaplastic thyroid cancer (ATC) models, prompting its
evaluation also as a candidate therapeutic in advanced ATC. Methods: A
multicenter single arm phase II trial of 800 mg pazopanib daily was
undertaken with the primary endpoint of RECIST response rate. The trial
was designed such that there would be a 90% chance of detecting a
response rate of �20% at the 0.10 significance level when the true tumor
response rate is �5%. A pre-specified stopping rule designated that
enrollment would cease unless 1 or more RECIST PRs�CRs were observed
in the first 14 of 33 potential patients. Eligibility required informed
consent, �18 years of age, performance status ECOG 0-2, systolic blood
pressure (BP) �140 mm Hg and diastolic BP �90 mm Hg at entry, QTc
interval �480 msecs, and measurable disease by RECIST criteria. Anatomical
imaging and toxicity evaluations were required every 4 weeks. Results:
Sixteen patients were enrolled. One patient withdrew prior to therapy,
leaving 15 evaluable patients – 33.3% were male, with a median age of 66
years (range 45-77); 11 of 15 patients had progressed through prior
systemic therapy. Four patients required 1-2 dose reductions, with the
most common severe toxicities (CTC-AE version 3.0 grades 3-5) hypertension
(13%) and pharyngolaryngeal pain (13%). Reasons for treatment
discontinuation included: disease progression (12 pts), death on study due
to a vascular event possibly related to treatment (1 pt.), and intolerability
(radiation recall tracheitis – 1 pt, and uncontrolled hypertension – 1 pt).
Although transient disease regression was observed in several patients,
there were no confirmed RECIST tumor responses, triggering study closure
at time of interim analysis. Two patients are alive with disease 9.9 months
and 2.9 years post-registration; the remaining 13 died of disease. The
median time to progression was 62 days and the median survival time was
111 days. Conclusions: Pazopanib has poor single agent activity in
advanced anaplastic thyroid cancer.
5546 General Poster Session (Board #22F), Sat, 1:15 PM-5:15 PM
The role of family caregiver in the head and neck cancer: Psychological
distress and quality of life evaluation. Presenting Author: Mario Airoldi, San
Giovanni Antica Sede Hospital, Turin, Italy
Background: The family caregiver (FCG) has become a hot topic. This figure
among head and neck cancer patients is still largely un-investigated; aim of
our study was: 1) to describe in a more detailed way the role of FCG, 2) to
evaluate quality of life (QoL) and psychological distress of FCGs and
patients 3) to investigate relationships between FCG’s wellbeing and
patient’s QoL and emotional pattern. Methods: Sixty couples of patients and
their caregivers were enrolled in this observational cross-sectional study
between April 2007 and May 2011 at 1st ENT Division, 2th Medical
Oncology Division and 2th Radiotherapy Division of San Giovanni Battista
Hospital of Turin. Inclusion criteria were: diagnosis of SCC, advanced stage
(III-IV), completion of curative treatment and no evidence of disease at the
enrolment. Psycho-oncological assessment was performed using: Distress
Thermometer (DT), Stay-Trait Anxiety Inventory Manual in Y1 and Y2 form
(STAI Y1-Y2), Beck Depression Inventory (BDI) and Montgomery-Asberg
Depression Rating Scale (MDRS), EORTC-QLQ-C30 and Head and Neck-35
module and Caregiver Quality of Life Index-Cancer (CQOLC). Results:
Patients: state and trait anxiety are 46,7% (STAI Y1 mean value 40,2�10,2;
cut-off 40) and 36,7% (STAI Y2 mean value 36,7�8,2; cut off 40)
respectively; self reported and clinician rated depression are 31,6% (BDI
mean value 8,2�5,3; cut-off 9) and 48,3% (MDRS mean value 7,9�5,9;
cut-off 6) respectively.CGs: state and trait anxiety are 50% (STAI Y1 mean
value 42,5�9,9; cut-off 40) and 41,7% (STAI Y2 mean value 39,1�8,7;
cut off 40) respectively; self reported and clinician rated depression are
28.3% (BDI mean value 7,3�4,7; cut-off 9) and 41.7% (MDRS mean
value 7,6�5,8; cut-off 6) respectively.Data analysis underlined a positive
association among emotional scales of patients and caregivers. Patients’
psychological aspects are negatively associated with caregivers’ QoL and
vice versa. Conclusions: Anxiety and depression are often present in FCGs
and cured HNC patients. Long term patient’s QoL is the result of a frail
balance between FCG and patiet emotional and psychological distress. A
psychological support for FCG could improve patient well-being.
Head and Neck Cancer
367s
5545^ General Poster Session (Board #22E), Sat, 1:15 PM-5:15 PM
A phase I study of everolimus (E) plus weekly cisplatin (CDDP) plus
intensity-modulated radiation therapy (IMRT) in head and neck (HN)
cancer. Presenting Author: Matthew G. Fury, Memorial Sloan-Kettering
Cancer Center, New York, NY
Background: The PI3K/mTOR/eIF4E pathway is upregulated in many HN
cancers, and expression of eIF4E in surgical margins has been associated
with increased risk of recurrence (Cancer Res 2007; 67:2160. Clin Cancer
Res 2004; 10:5820. JCO 1999; 17:2909). Daily E � weekly CDDP was
well tolerated in a phase I study for patients with advanced solid tumors
(Cancer Chemother Pharmacol 2011 Sep 13; Epub ahead of print]. E
achieves radiosensitization in pre-clinical models. This study evaluated
weekly CDDP � daily E given concurrently with IMRT in HN cancer.
Methods: This was a single institution phase I study with a standard 3 � 3
dose escalation plan. Patients (pts) received standard definitive IMRT (66
Gy resected tumors, 70 Gy unresected tumors) concurrent with CDDP 30
mg/m2 weekly X 6 and daily oral E according to the dose escalation plan.
Four dose levels (DLs) of daily oral E were planned: 2.5 mg, 5 mg, 7.5 mg,
and 10 mg. Toxicities were recorded according to NCI CTCAE v.3. Results:
Thirteen (9M, 4F) pts enrolled, with median age 52y (range, 37 – 65y) and
median KPS 90 (range, 80-100). Primary sites: oral cavity (4), salivary
gland (4), oropharynx (2), nasopharynx (1), scalp (1), unknown primary (1).
Stage: IVA (11), IVB (1), II (1). Prior treatment: surgery (10), chemotherapy
(2). The most common � G.3 treatment related AEs were mucositis
(functional 62%, clinical 31%), oral pain (31%), and lymphopenia (31%).
There were no DLTs among 3 patients at DL1 or the first 3 patients at DL2.
Among 4 pts at DL3, there were 2 DLTs: grade 3 mucositis with failure to
thrive, and grade 3 mucositis with hypoxia. Among 3 additional patients
enrolled at DL2, there was one 1 DLT: grade 3 mucositis with inability to
tolerate E. There were no treatment-related deaths. With a median
follow-up of 8.9 months, 3 patients have experienced recurrent disease,
one of whom has died of disease. Median PFS has not been reached. Tissue
correlates in process. Conclusions: When administered with weekly CDDP
(30 mg/m2 ) and definitive IMRT for HN cancer, the phase II recommended
dose of E is 5 mg/day.
5547 General Poster Session (Board #22G), Sat, 1:15 PM-5:15 PM
Antitumor activity of cabozantinib (XL184) in a cohort of patients (pts) with
differentiated thyroid cancer (DTC). Presenting Author: Maria E. Cabanillas,
University of Texas M. D. Anderson Cancer Center, Houston, TX
Background: Cabozantinib (cabo) is an oral, potent inhibitor of MET,
VEGFR2, and RET that is currently undergoing evaluation in several
oncology indications. Differentiated thyroid cancer (DTC) pts were included
in this study based on involvement of the MET, VEGFR, and RET signaling
pathways in this disease. The primary objective of this study is to determine
the effect of cabo on single dose PK of the CYP2C8 substrate rosiglitazone
(rosi). Anti-tumor activity and safety were also evaluated. Methods: Metastatic
DTC pts who were enrolled to this study were required to be
RAI-refractory, have progressed on standard therapies and have measurable
disease. Cabo was given daily at a dose of 140 mg free base
(equivalent to 175mg salt form) starting at Day 2. Rosi (4mg) was given Day
1 and Day 22 to complete PK assessment for drug-drug interaction (DDI).
Cabo was continued until PD. On Day 57 and every 8 weeks thereafter
subjects underwent tumor assessments by mRECIST. Results: 15 DTC pts
were enrolled. Median number of prior regimens was 2 (11/15 pts had at
least 1 prior VEGFR inhibitor). 8/15 pts (53%) had confirmed PRs
including 1 pt with marked improvement of a bone infiltrating lesion; 6
(40%) had best response of SD; all 14 pts with �1 post-baseline scan
experienced tumor regression (range: -9 to -55%). Disease control rate (PR
� SD): 80% at 16 weeks; 10/15 (67%) remain on cabo with a median
follow-up of 7.3 months. Median PFS and OS have not been reached. Most
common Gr 3/4 AEs were: diarrhea (20%), lipase increased (20%),
hypertension (13%) and palmar-plantar erythrodyesthesia (13%); one
related Gr 5 event reported: hemoptysis due to aorto-trachael fistula in a pt
with history of prior mediastinal XRT and extensive neck surgeries. PK data
suggest that clinically relevant doses of cabo do not alter the Cmax or
AUC of rosi, consistent with no inhibition of CYP2C8. Conclusions: In
0-24h
pts with DTC, cabo treatment resulted in substantial anti-tumor activity.
The safety profile of cabo was comparable to that seen with other VEGFR
TKIs. PK data suggest no DDI between cabo and rosi (CYP2C8 substrate).
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