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

8600 General Poster Session (Board #39B), Sun, 8:00 AM-12:00 PM
Preoperative peripheral blood lymphocyte/monocyte ratio and survival in
patients with resected stage IV melanoma. Presenting Author: Nicole M.
Rochet, Mayo Clinic College of Medicine, Rochester, MN
Background: The prognosis of stage IV melanoma patients remains poor.
Published results have suggested that components of the complete blood
count have significant prognostic value in several malignancies. Among the
most studied were the absolute lymphocyte count (ALC), and absolute
monocyte count (AMC) on clinical outcomes of patients with lymphoid
malignancies. Thus, we sought to investigate if the pre-operative ALC
(ALC-PO), AMC (AMC-PO) and ALC/AMC ratio (ALC/AMC-PO) affects the
risk of disease recurrence and survival after complete surgical resection of
metastatic melanoma. Methods: We studied 66 stage IV, resected melanoma
patients followed at Mayo Clinic from 2000 to 2010. Log rank
chi-square analysis was used to determine the best cut-off values for each
pre-operative variable, while proportional hazards models were used to
compared survival. Results: The median follow-up of the cohort was 24
months (range: 2.3 – 117 months). ALC-PO, AMC-PO and ALC/AMC-PO, as
continuous variables, were all identified as prognostic factors for both
relapse-free survival (RFS) and overall survival (OS). The best cut-off values
for ALC-PO, AMC-PO and ALC/AMC-PO were 1.9; 0.62; and 2.05,
respectively. Using Kaplan-Meier analysis, patients with an ALC-PO � 1.9
x109 /L experienced superior OS and RFS compared with ALC-PO � 1.9 x
109 /L patients [median OS of 58 months vs. 34 months, p � 0.04; median
RFS of 14 months vs. 5 months, p � 0.009]. Conversely, a low AMC-PO
(�0.62 x 109 /L) was associated with better OS and RFS compared with
higher AMC-PO (� 0.62 x 109 /L): [median OS of 47 months vs. 14 months,
p � 0.007; median RFS of 9 months vs. 5 months, p � 0.02]. When the
ALC-PO and AMC-PO were combined as an ALC/AMC ratio, the group with
an ALC/AMC-PO � 2.05 experienced a superior OS and RFS compared to
patients with ALC/AMC-PO � 2.05: [median OS of 49 months vs. 12
months, p � 0.0001; median RFS of 10 months vs. 4 months, p �
0.0001]. Multivariate analysis showed ALC/AMC-PO to be an independent
prognostic factor for RFS and OS (HR � 0.32, p � 0.003; HR � 0.23, p �
0.002). Conclusions: Our study showed, that ALC/AMC-PO ratio is an
independent prognostic factor for RFS and OS in patients undergoing
resection of metastatic (stage IV) melanoma.
TPS8602 General Poster Session (Board #39D), Sun, 8:00 AM-12:00 PM
A phase I/II trial of BKM120 combined with vemurafenib (PLX4032) in
BRAFV600E/k mutant advanced melanoma. Presenting Author: Andrea
Kantor, University of California, San Francisco, San Francisco, CA
Background: Vemurafenib induces transient objective responses in half of
BRAFV600E mutant melanoma patients and a median PFS of 5.3 months
(NEJM. 2011;364:2507-2516). BRAF mutations are not sufficient to
cause melanoma, but the combination of BRAFV600E mutation and PTEN
loss is sufficient to recapitulate the malignant melanoma phenotype in vivo
(Nat. Genet. 2009;41:544-552). PTEN loss and PI3K activation are
common in BRAF mutant metastatic melanoma, and PI3K activation has
been implicated as a cause acquired resistance to BRAF inhibitors (Cancer
Cell. 2010;18:683-695). This phase I/II study is the first trial to test the
safety and efficacy of combining a potent BRAF inhibitor, vemurafenib,
with a potent PI3K inhibitor, BKM120, in patients with metastatic BRAF
mutant melanoma. Methods: Design: Phase I patients receive a single dose
of oral BKM120 (d -7) then vemurafenib twice daily with BKM120 daily
(starting on c1d1). PK analysis is performed for BKM120 alone and for
both drugs in combination. Doses of both drugs will be escalated in 3�3
scheme. Phase II patients receive continuous dosing of vemurafenib twice
daily and BKM120 daily. Serial biopsies for PD and mRNA expression
analyses are required for patients with visible or palpable tumors. Reimaging
will be performed every 8 weeks.Eligibility: This study is enrolling
BRAFV600E/K mutant metastatic melanoma patients with no prior exposure
to BRAF inhibitors or PI3K inhibitors, ECOG PS � 2 and adequate organ
function. Endpoints: The primary endpoint for phase 1 is the recommended
phase 2 dose of the combination. The primary endpoint for phase II is the 6
month PFS rate. Secondary endpoints include median PFS and OS.
Baseline PTEN expression and changes is pS6 protein levels will be
examined as predictors of efficacy, and changes in gene expression profiles
will be assessed. Summary: This is the first trial examining the safety and
efficacy of combined BRAF/PI3K inhibition in BRAF mutant melanoma
patients.
Melanoma/Skin Cancers
565s
8601 General Poster Session (Board #39C), Sun, 8:00 AM-12:00 PM
Comparison of sun protection modalities in parents and children. Presenting
Author: Laurent Mortier, Clinique de Dermatologie, CHRU de Lille,
Lille, France
Background: Routine sun protection is recommended to prevent skin
cancer. Our aims were to examine and compare, in an observational survey,
modalities of sun protection in parents and their children. Methods: This
French nationwide observational survey, EDIFICE melanoma, was conducted
through phone interviews among a representative sample of 1502
subjects aged � 18 years old, using the quota method. The survey took
place shortly after summer, from 28 Sep 2011 to 20 Oct 2011. Results:
1502 subjects were interviewed. Among them 1067 reported that they
were sun-exposed (SE) at least ten days per year, 748 were parents, and
319 had no children. Sun protection measures seemed well done both in
“parents” and “nonparents” groups: 74% used clothing; 43% used
sunscreen, which was regularly renewed in 57% of cases. Sun protection
measures used by SE parents for SE children were superior, both qualitatively
and quantitatively to those used for themselves, ie 50% of parents
reported using clothing, sunglasses and hat for their children vs 23% for
themselves. In 87% of cases, parents reported regular re-application of
sunscreen for their children vs 44% for themselves. The sunscreen SPF
(Sun Protection Factor) was significantly lower for parents than for their
children. Such data are in accordance with Buller et al. (Oncol Nurs Forum
1995), but contrast with the findings of Riordan et al. (J Pediatr 2003) with
children being significantly less likely to wear sunglasses and to adopt sun
avoidance habits than their parents. Conclusions: Sun protection awareness
seems globally satisfying in the French population, with no difference
between adult parents and nonparents, and is similar to that reported in
Germany (Gambicher JEADV 2010), but seems better than in the US
(Buller et al. JAAD 2011). Furthermore, French parents use sun protective
measures qualitatively and quantitatively more efficiently for their children
than for themselves.
TPS8603 General Poster Session (Board #39E), Sun, 8:00 AM-12:00 PM
CA184-161: A phase I/II trial of vemurafenib and ipilimumab in patients
with BRAF V600 mutation-positive metastatic melanoma. Presenting
Author: Antoni Ribas, University of California, Los Angeles, Los Angeles,
CA
Background: Ipilimumab (ipi) is a fully human monoclonal antibody that
blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4) to augment antitumor
immune responses. Ipi significantly improved overall survival (OS) in two
separate phase III trials of metastatic melanoma (MM): (1) at 3 mg/kg as
monotherapy in previously treated patients and (2) at 10 mg/kg combined
with dacarbazine in previously untreated patients. The most common
drug-related adverse events with ipi were immune-related, and were
generally reversible using treatment guidelines. Vemurafenib (vem) is a
potent inhibitor of BRAF V600E-mutated kinase, which occurs in ~50% of
MM. In clinical studies, vem produced objective response rates of ~50%
with a significant improvement in the rate of OS in patients with previously
untreated BRAF V600-positive MM. The purpose of this phase I/II study is
to determine the safety and feasibility of ipi plus vem in patients with BRAF
V600-positive MM, and to evaluate the efficacy of the combination in
comparison to historical results observed with each agent alone. Methods:
In phase I, an escalating dose design is used to assess safety/tolerability
and to determine the maximum tolerated dose (MTD) of each agent. Vem
will initially be given alone for 28 days at 960 mg p.o. BID, followed by vem
in combination with ipi i.v. at 3 mg/kg [induction (q3w x 4) and
maintenance (q12w)]. The next cohort will receive vem at 960 mg plus ipi
increased to a dose of 10 mg/kg. Phase I will enroll an estimated 20
patients who have not previously received a CTLA-4 antagonist or BRAF
inhibitor. If new or heightened frequency or severity of toxicities is not
observed, a phase II single-arm extension at the MTD of each agent will be
conducted in patients with previously untreated MM. The primary objectives
of phase II (estimated enrollment of 30 patients) are to obtain
preliminary evidence of efficacy (OS, 1- and 2-year survival rates) and to
evaluate safety of the combination. Major inclusion criteria are � 18 years
of age, BRAF V600-positive MM, measurable tumor, no active brain
metastasis, and an ECOG PS of 0-1. The first patient was enrolled in
November 2011 and enrollment is ongoing (ClinicalTrials.gov identifier:
NCT01400451).
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