Real-World Effectiveness of First-Line Ipilimumab for Advanced Melanoma in
the U.S. Community Setting
1Bristol-Myers
Debra
2
Rembert,
Timothy
Squibb, Plainsboro, NJ, USA,
Abstract
In clinical trials, the immune-oncology therapy ipilimumab (Yervoy®) has demonstrated prolonged overall survival (OS) in treatment (Rx)-naïve and pretreated advanced
melanoma (AM) patients (pts). This observational study (CA184-332) will describe pt
and disease characteristics, patterns of care, and outcomes of Rx-naïve AM pts
initiating ipilimumab (IPI) (3 mg/kg every 3 weeks x 4) in the U.S. community setting
over a 4 year period. Adult pts with unresectable stage III or stage IV AM who had
received ≥1 dose of first-line IPI 3 mg/kg (April 2011 – September 2012) were
identified retrospectively in U.S. Oncology practices utilizing the iKnowMed (iKM)
electronic medical record system. Clinical data were obtained using programmatic
queries in iKM and medical chart abstraction. This interim analysis reports on the first
90 pts for whom at least 12 months had elapsed since IPI initiation. The majority of
the 90 pts were male (66.7%) with a mean age of 64 years (SD=13) at IPI initiation.
Primary sites at initial melanoma diagnosis were cutaneous (92.2%), ocular (3.3%),
and anorectal (2.2%). BRAF mutational testing occurred in 68.9% of pts and of those
tested, 22.6% were BRAF mutation positive. At AM diagnosis, 23.3%, 30%, and
44.5% of pts were stage M1a, M1b, and M1c, respectively; none had unresectable
stage III AM. By IPI initiation, brain metastases were identified in 31.1% of pts. At AM
diagnosis, 64.5% and 27.8% of pts had ECOG PS 0 and 1, respectively, and 39.4%
of the 71 pts with available results had elevated LDH. Overall median follow-up was
9.6 months (range 0.4–22). From IPI initiation, median OS was 11.5 months (95% CI
7.2, --) and the 1-year survival rate was 49.4% (95% CI 38.3-59.6%). This study
provides community-based, real world evidence of an OS profile of first line IPI
3 mg/kg in Rx-naïve AM that is consistent with clinical trials of IPI.
2The
1
Juday,
John R.
1
Penrod,
Rahul
2
Dhanda,
Debra
2
Patt
U.S. Oncology Network, McKesson Specialty Health, Houston, TX, USA
Results (continued)
Methods (continued)
16,358 melanoma patients treated at
MSH/USON sites with full EHR capabilities
Excluding 12,382 (76%) with
no evidence of AM
3,976 (24%) patients with AM
Excluding 429* (12%):
108 clinical trial (25%) and
329 (77%) other tumor types
• In the Kaplan-Meier analysis for the overall sample, the median OS was
11.5 months (95% CI 7.2,--) from IPI initiation (Figure 1) with a 1-year survival
rate of 49.4% (95% CI 38.3-59.6%). Overall median follow-up was 9.6 months
from IPI initiation (range CI 2.8–14.4)
• For patients without brain metastases, the median survival was 14.2 months
(95% CI 8.9,--). Patients with brain metastases had 5.4 months (95% CI
2.4–16.6) of median survival (Figure 2)
• 48 of 90 patients (53.3%) had died by the end of follow-up, including 29 of 62
patients without brain metastases (46.8%) and 19 of 28 patients with brain
metastases (67.9%)
3,547 (89%) AM patients
1.0
Censored
Excluding 3,439 (97%) without
first-line IPI
108 (3%) started IPI in first line
Excluding 18 (17%) with previous
first-line therapy
90 (83%) IPI-naïve patients
0.8
Survival Probability
Schiffon L.
1
Wong,
Median OS: 11.5 months
1-year survival: 49.4%
0.6
0.4
0.2
*8 patients overlapped between the two criteria.
• Ipilimumab (IPI) is a fully human monoclonal antibody that potentiates antitumor
T-cell response and was the first therapy to prolong survival of advanced
melanoma (AM) patients in a phase III trial; this pivotal trial of previously treated
AM patients also included those with brain metastases.1 The U.S. Food and Drug
Administration approved an IPI monotherapy induction regimen (3 mg/kg every
3 weeks for 4 doses) for the treatment of AM in 2011
• A second phase III trial showed that 10 mg/kg IPI plus dacarbazine prolonged
survival versus dacarbazine alone in treatment-naïve AM patients.2 However,
this dosing and combination are not currently approved in the United States
• There are limited data regarding first-line IPI 3 mg/kg monotherapy in the
community setting
90
Results
• The majority of the 90 patients were male (66.7%) with a mean age of 64 years
(SD=13) at IPI initiation. For the 64 patients of known ethnicities, 95.3% were
white. The most common primary site at initial diagnosis was cutaneous (92.2%)
• BRAF-mutational testing occurred in 68.9% of patients, and of those tested,
22.6% were BRAF mutation-positive
• At baseline, 64.5% and 27.8% of patients were ECOG 0 and 1, respectively,
and 31.1% had lactate dehydrogenase > upper normal limit. By IPI initiation,
over 50% of patients had lung metastases
Table 1. Demography and Clinical Characteristics at Baseline
Objectives
• Describe the baseline demographic and clinical characteristics of AM patients
treated with first-line IPI
• Evaluate overall survival (OS) in the overall first-line IPI patient population and
a subgroup of first-line IPI patients with brain metastases
Feature
Number of
Patients
(N=90)
Age at IPI initiation
(years)
Mean (SD)
64 (13)
Methods
<65
42 (46.7)
• CA184-332 is a retrospective observational cohort study of patients with
advanced (unresectable and metastatic) melanoma who were treated with
≥1 dose of 3 mg/kg IPI monotherapy in first line between April 2011 and
September 2012 in the community clinical practices of the McKesson Specialty
Health/US Oncology Network (MSH/USON). MSH/USON covers a vast
geographical area in the United States, providing strong generalizability of study
results for U.S. community clinical practices. The target cohort will be followed
for 4 years
• This interim analysis reports on 90 patients initiating IPI between April 1, 2011
and March 31, 2012, the subset for whom at least 12 months had elapsed since
IPI initiation at the time of the analysis. A prior presentation reported on the
61 patients for whom at least 12 months had elapsed since initiation at the time
of that analysis3
≥65
48 (53.3)
Inclusion Criteria
• Patients with unresectable or metastatic melanoma who were initially diagnosed
at ≥11 years of age and initiated IPI monotherapy with a dose of 3 mg/kg in the
first-line setting
• Patients who received care at an MSH/USON practice using full iKM EHR
capabilities over the entire study period
Exclusion Criteria
• Patients with prior systemic treatment for unresectable or advanced disease
• Patients with current or pending enrollment in clinical trials during the study period
and follow-up
• Patients treated for other cancers
• Patients who were not IPI treatment-naïve
Outcomes
• OS was defined as the time from initiation of IPI until death from any cause for the
overall population as well as a subgroup by brain metastasis status (yes/no). For
patients who were still alive, they were censored at the last known alive date
Statistical Analysis
• Survival data were analyzed using the Kaplan-Meier method
Number of
Patients
(N=90)
Feature
M-stage
Median (range)
Data Source
• Data were abstracted via programmatic query of MSH/USON’s iKnowMed (iKM)
electronic health record (EHR) system, electronic medical record chart review,
and the Social Security Death Master File
66 (21-91)
Gender
30 (33.3)
Male
60 (66.7)
Race
African American
1 (1.1)
Asian
1 (1.1)
Hispanic/Latino
1 (1.1)
M1a
21 (23.3)
M1b
27 (30.0)
M1c
40 (44.5)
Unknown/Missing
2 (2.2)
ECOG performance status
58 (64.5)
1
25 (27.8)
≥2
3 (3.3)
Unknown/Missing
4 (4.4)
LDH
Elevated (>upper normal
limit)
28 (31.1)
White
61 (67.8)
Normal
43 (47.8)
Unknown/Missing
26 (28.9)
Unknown/Missing
19 (21.1)
Primary diagnosis site
Location of metastasis
83 (92.2)
Lung
47 (52.2)
Non-cutaneous
6 (6.6)
Lymph nodes
41 (45.6)
Anorectal
2 (2.2)
Liver
37 (41.1)
Ocular
3 (3.3)
Brain
28 (31.1)
Vulvar
1 (1.1)
Subcutaneous tissues
16 (17.8)
1 (1.1)
Adrenal gland
10 (11.1)
Unknown/Missing
74
BRAF-mutation testing (at any time)
Gastrointestinal
7 (7.8)
Mutation negative
48 (53.3)
Distant skin
5 (5.6)
Mutation positive
14 (15.6)
Spleen
1 (1.1)
Unknown/Missing
28 (31.1)
NRAS-mutation testing (at any time)
Time from initial diagnosis to IPI
initiation (months)
Mutation negative
3 (3.3)
Mean (SD)
Mutation positive
2 (2.2)
Median (range)
Unknown/Missing
85 (94.5)
LDH, lactate dehydrogenase.
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24.8 (48.9)
9.0 (0.1-352.5)
65
60
56
53
52
50
46
41
39
37
31
27
20
16
11
7
7
3
3
0
5
10
15
20
Overall Survival Measured From Ipilimumab Initiation (months)
Figure 1. Kaplan-Meier Plot for Overall Survival From IPI Initiation
1.0
Censored
0.8
Yes Median OS: 5.4 months
No Median OS: 14.2 months
0.6
0.4
0.2
0.0
NO
YES
0
Female
Cutaneous
87
0
Survival Probability
Background
0.0
62
28
61
26
0
53
21
49
16
45
15
42
14
41
12
40
12
38
12
35
11
31
10
30
9
28
9
24
7
20
7
14
6
11
5
7
4
5
2
5
2
2
1
2
1
0
0
5
10
15
20
Overall Survival Measured From Ipilimumab Initiation (months)
Brain mets
No
25
Yes
Figure 2. Kaplan-Meier Plot for Overall Survival From IPI Initiation by Brain Metastasis
Limitations
• The limitations of this study include potential loss to follow-up, missing data, and
potential for selection bias associated with the study’s retrospective design
Conclusions
• Study results (median OS: 11.5 months, 49.4% 1-year survival rate) are
consistent with clinical trials1,2 that have demonstrated the survival benefits
of IPI for the treatment of AM
• Patients with brain metastasis, which is a poor prognostic factor in AM, had
a median OS of 5.4 months in contrast to patients without brain metastasis
where median OS was 14.2 months
• This is one of the largest studies of IPI 3 mg/kg monotherapy in treatmentnaïve AM and provides “real-world” evidence that supports the results seen in
clinical trials
• These data affirm the survival experience of IPI in a U.S. community-based
setting in patients with a broad range of clinical characteristics and
geographic locations
References
1. Hodi FS, et al. N Engl J Med. 2010;363(8):711-723.
2. Robert C, et al. N Engl J Med. 2011;364(26):2517-2526.
3. Patt D, et al. ECCO-ESMO-ESTRO, Amsterdam, September 2013.
Disclosures
Study support and funding were provided by Bristol-Myers Squibb. John Penrod and Timothy
Juday are employees of Bristol-Myers Squibb. Schiffon Wong was an employee
of Bristol-Myers Squibb at the time this analysis was prepared
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Presented at the 10th International Meeting of the Society for Melanoma Research; November 17–20, 2013; Philadelphia, PA, USA