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

508s Lung Cancer—Non-small Cell Metastatic
TPS7615 General Poster Session (Board #54A), Sat, 1:15 PM-5:15 PM
ARCHER: Dacomitinib (D; PF-00299804) versus erlotinib (E) for advanced
(adv) non-small cell lung cancer (NSCLC)—A randomized double-blind
phase III study. Presenting Author: Michael Boyer, Sydney Cancer Centre,
Camperdown, Australia
Background: D is a highly selective irreversible small molecule inhibitor of
all catalytically active members of the HER (human epidermal growth
factor receptor) family of tyrosine kinases. In a randomized phase II trial in
patients (pts) who had received 1–2 prior systemic therapy regimens for adv
NSCLC, D demonstrated significantly longer progression-free survival (PFS)
vs. E in the overall population (12.4 vs. 8.3 weeks; HR�0.66, P�0.012),
with benefit consistent across several clinical and molecular subgroups.
Median PFS in the KRAS wild-type (WT) subgroup was 16.1 vs. 8.3 weeks
for D and E, respectively (HR�0.55, P�0.006). Methods: Based on phase
II data, a randomized, double-blinded phase III clinical trial (ARCHER;
NCT01360554) was designed to compare the efficacy of D with E in two
co-primary populations of pts with adv NSCLC: (a) all enrolled pts with adv
NSCLC, and (b) pts with KRAS WT NSCLC. Pts with locally adv/metastatic
pathologically confirmed NSCLC, radiologically measurable disease, 1 or 2
prior chemotherapy regimens, ECOG PS 0–2, and tissue available for
molecular analysis will be randomized to receive D 45 mg or E 150 mg
orally once daily. As of Jan 31, 2012, 117 of a planned 800 pts have been
enrolled. The primary endpoint is PFS. Secondary endpoints include overall
survival, objective response rate, duration of response, safety and tolerability,
and pt-reported outcomes of health-related quality of life and disease-/
treatment-related symptoms. Study design provides 90% and 80% power
to detect �33% and �45% improvement in PFS in all pts receiving D vs.
E, and in pts with KRAS W T NSCLC, respectively, and HR �0.75 and
�0.69 using a 1-sided stratified log-rank test at a significance level of
0.015 and 0.01, respectively. The final primary analysis stratified log-rank
test will include ECOG PS, KRAS mutation status and EGFR mutation
status as stratification factors. The sample sizes above will also allow the
assessment of OS in the co-primary populations with adequate power.
Post-hoc analyses will be performed to explore EGFR, HER family, and
KRAS mutation status, as well as other tumor-derived biomarkers collected
from all pts in this trial.
TPS7617 General Poster Session (Board #54C), Sat, 1:15 PM-5:15 PM
Prophylactic cranial irradiation after reaching complete response, partial
response, or stable disease in non-small cell lung cancer patients treated
with epidermal growth factor receptor tyrosine kinase inhibitors (ProACT).
Presenting Author: Amanda Tufman, Ludwig Maximilians University Munich,
Munich, Germany
Background: Patients with non-small cell lung cancer (NSCLC) who respond
to treatment with epidermal growth factor receptor tyrosine kinase inhibitors
(EGFR TKIs) seem to be at increased risk of central nervous system
relapse, and may benefit from prophylactic cranial irradiation (PCI) more
than other NSCLC patients. Methods: This study investigates the safety and
efficacy of combining PCI with EGFR TKIs in stage IV NSCLC. Patients with
stage IV NSCLC, no evidence of brain metastases, and an indication for first
or later line therapy with an EGFR TKI will be enrolled. Those with complete
response (CR), partial response (PR), or stable disease (SD) following 6
weeks of therapy and no evidence of brain metastases on MRI will be
treated with PCI. Neurocognitive function, depression indices, quality of
life, symptoms, and ability to function independantly will be assessed at
baseline, before PCI, and at 6 week and then 3 month intervals following
PCI. MRI will be repeated 6 weeks following PCI and at 3 month intervals,
and serum markers of blood brain barrier permeability (neuron-specific
enolase (NSE), protein S100 beta) will be assessed at all visits. Safety data
will be formally reviewed after the first 10 patients. The primary endpoint
for efficacy is overall survival. Secondary endpoints include progression
free survival, site of progression, quality of life and neurological disability.
Planed subgroup analyses based on mutation status, line of treatment with
TKIs, comorbidity, precise histology and molecular biology will be carried
out.
TPS7616 General Poster Session (Board #54B), Sat, 1:15 PM-5:15 PM
The MetLUNG study: A randomized, double-blind, phase III study of
onartuzumab (MetMAb) plus erlotinib versus placebo plus erlotinib in
patients with advanced, MET-positive non-small cell lung cancer (NSCLC).
Presenting Author: David R. Spigel, Sarah Cannon Research Institute/
Tennessee Oncology PLLC, Nashville, TN
Background: Increased Met signaling is associated with poor prognosis in
NSCLC and can result in acquired resistance to epidermal growth factor
receptor (EGFR)-targeted drugs in EGFR-mutant lung tumors. Onartuzumab
(MetMAb) is a humanized monovalent monoclonal antibody that
binds to Met with high specificity, preventing HGF ligand binding and
blocking downstream signaling. Onartuzumab has shown anticancer activity
in preclinical studies (Merchant et al. AACR 2008:Abstr. 1336) and in a
phase I study of patients with advanced solid tumors (Moss et al. Ann Oncol
2010;21(Suppl. 8):Abstr. 504P). In a phase II study, patients with
Met-positive tumors (�50% of tumor cells stain 2� or 3� intensity by IHC)
(Met Dx�) who received onartuzumab � erlotinib had nearly twofold
reduction in the risk of disease progression and threefold reduction in the
risk of death compared with erlotinib alone (Spigel et al. J Clin Oncol
2011;29(Suppl.):Abstr. 7505). An increased incidence of peripheral
edema was observed in patients treated with onartuzumab. Methods: This is
a randomized, phase III, multicenter, double-blind, placebo-controlled
study. Adults with Met Dx� tumors who failed at least 1 but no more than 2
prior lines of platinum-based chemotherapy for advanced NSCLC are
eligible. Around 480 patients will receive (1:1) erlotinib (150 mg PO daily)
� placebo or onartuzumab (15 mg/kg IV Q3W) until disease progression,
unacceptable toxicity, patient/physician decision to discontinue, or death.
Patients are stratified for Met expression (2� vs 3�), prior lines of therapy
(1 vs 2), histology (squamous vs nonsquamous) and EGFR-activating
mutation status (yes vs no). The primary endpoint is OS. Secondary
endpoints include PFS, response rates, safety, patient-reported outcomes,
and PK. An IDMC will monitor safety every 6 months after the 1st patient is
enrolled and evaluate 1 interim analysis when ~67% of the total OS events
have occurred. This study is open for accrual; further details can be found
on ClinicalTrials.gov (NCT01456325).
TPS7618 General Poster Session (Board #54D), Sat, 1:15 PM-5:15 PM
Weekly nab-paclitaxel in combination with carboplatin as first-line therapy
in patients (pts) with advanced non-small cell lung cancer (NSCLC):
Analysis of patient-reported neuropathy and taxane-associated symptoms.
Presenting Author: Vera Hirsh, McGill University – Royal Victoria Hospital,
Montreal, QC, Canada
Background: Neuropathy and its associated symptoms are dose-limiting
toxicities of taxane-based regimens. Measuring disease symptoms has
utility for maintaining a balance between the benefits and costs of
treatment. In a phase III trial nab-paclitaxel (nab-P, 130 nm albuminbound
paclitaxel particles) � carboplatin (C) vs solvent-based paclitaxel
(sb-P) � C significantly improved the primary endpoint of overall response
rate (ORR) (25% vs 33%, P � 0.005), with a 1-month improvement in
median overall survival (OS; P � NS), and an improved tolerability profile in
pts with advanced NSCLC. Here we report on patient-assessed neuropathy
and taxane-associated symptoms, important factors in a palliative patient
setting. Methods: Pts with untreated stage IIIB/IV NSCLC were randomized
1:1 to C AUC 6 day 1 and either nab-P 100 mg/m2 on days 1, 8, 15 (n �
521) or sb-P 200 mg/m2 day1(n� 531) q 21 days. Treatment was
continued until disease progression. Safety was assessed per the Common
Terminology Criteria for Adverse Events (CTCAE) v3.0. The mean change
from baseline to day 1 of each cycle for the neuropathy, pain, and hearing
subscales of Functional Assessment of Cancer Therapy (FACT)-Taxane v
4.0 were assessed. Results: 1031 (98%) pts completed FACT-Taxane at
baseline, and 987 (94%) during follow-up or at completion of treatment.
Baseline scores for neuropathy and pain were well balanced. Significant
treatment effects favoring nab-P/C were noted for patient-reported neuropathy
(P � 0.001), neuropathic pain hands/feet (P � 0.001), and hearing
loss (P � 0.002). Physician-assessed rates of neuropathy were significantly
lower in the nab-P/C arm vs the sb-P/C arm: 47% vs 63%, P � 0.001, all
grades; 3% vs 12%, P � 0.001, grade 3/4, respectively. More pts treated
with nab-P/C vs sb-P/C had no neuropathy (53% vs 47%, P � 0.001).
Conclusions: nab-P/C was associated with statistically and clinically
significant reductions in patient-reported neuropathy, neuropathic pain in
the hands and feet, and hearing loss compared with sb-P/C. Patientreported
outcomes for neuropathy were consistent with physician assessment.
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