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Annals of Oncology
12 and repeated every 4 weeks until disease progression or unacceptable toxicity
occurred. The primary endpoint was progression-free survival (PFS) rate at 6
months. Responses were evaluated using immune-related response criteria.
Results: Sixty-four pts were enrolled and received at least one dose of study drug. All
pts were included in the analysis. With a median follow-up of 51 weeks, the PFS rate
at 6 months was 45%, exceeding the proposed rate of 30%, and the median PFS was
22 weeks. There were 10 (15.6%) confirmed complete responses and 10 (15.6%)
confirmed partial responses. To date, median overall survival has not been reached.
Among many variables including age, gender, ECOG PS, and stage, there was a
statistically significant difference in PFS in the group of patients with bone metastasis
and those without bone metastasis.
Conclusion: At a median follow-up of 51 weeks, the overall response rate in this
study is 31%. Ipi at 10 mg/kg in combination with Tem given in an induction
followed by maintenance fashion is safe, well-tolerated, and efficacious in MM. The
primary endpoint of 6-month PFS has been reached and exceeded.
Factors Associated with PFS
No. of Pts
Median PFS
(weeks)
Univariate
P-Value
Hazard
Ratio 95% CI
Bone Mets
No 57 24 — 1.00 —
Yes 7 12 0.01 2.73 1.20 – 6.20
Disclosure: S. Patel: Research funding from Bristol-Myers Squibb. W. Hwu: Research
funding from Merck Research funding from Bristol-Myers Squibb. K. Kim: Research
funding from Bristol-Myers Squibb Advisory board, honoraria from Bristol-Myers
Squibb. All other authors have declared no conflicts of interest.
1127P FOUR-YEAR SURVIVAL UPDATE FOR METASTATIC
MELANOMA (MM) PATIENTS (PTS) TREATED WITH
IPILIMUMAB (IPI) + DACARBAZINE (DTIC) ON PHASE 3
STUDY CA184-024
M. Maio 1 , I. Bondarenko 2 , C. Robert 3 , L. Thomas 4 , C. Garbe 5 , A. Testori 6 ,
S. Francis 7 , K. Chin 8 , J. Wolchok 9
1 Department of Oncology, Azienda Ospedaliera Senese - Medical Oncology and
Immunotherapy Unit, Siena, ITALY, 2 Department of Oncology, Radiodiagnosis
and Radioth, Dnipropetrovsk Municipal Clinical Hospital #4, Dnepropetrovsk,
UKRAINE, 3 Melanoma Unit, Institute Gustave Roussy, Villejuif, FRANCE,
4 Department of Dermatology, Lyon 1 University Centre Hospitalier Lyon Sud,
Villeurbanne, FRANCE, 5 Oncology, University Medical Center, Tuebingen,
GERMANY, 6 Melanoma Division, European Institute of Oncology, Milan, ITALY,
7 Global Biometrics Sciences, Bristol-Myers Squibb, Braine-l’Alleud, BELGIUM,
8 Global Clinical Research - Oncology, Bristol-Myers Squibb, Wallingford, CT,
UNITED STATES OF AMERICA, 9 Melanoma-sarcoma Division, Memorial
Sloan-Kettering Cancer Center, New York, NY, UNITED STATES OF AMERICA
Background: Data from clinical trials suggest a long-term survival effect (beyond 4
yrs) of IPI therapy in some pts with MM. An analysis of 177 pts from 3 phase I/II
IPI studies conducted at NCI demonstrated 5-yr survival rates of 13-25% (Prieto,
et al., CCR 2012). In other phase II trials, IPI monotherapy was associated with
long-term survival of 4+ yrs in some pts with MM (Wolchok, et al., 2011 PIM). IPI
in combination with DTIC in previously untreated MM patients significantly
improved OS in phase III study CA184-024 (Robert, et al, NEJM 2011). Safety data
from study 024 has been previously published. Here we report 4-yr survival data
from study 024, the longest IPI survival follow-up from a phase III study.
Methods: Pts with treatment-naive MM were randomized to receive either IPI (10
mg/kg) + DTIC (850 mg/m 2 ) or placebo + DTIC (850 mg/m 2 ) given at Wks 1, 4, 7,
10 followed by DTIC q 3 wks through Wk 22. Pts with stable disease or better then
received IPI or placebo q 12 wks as maintenance. This analysis reports OS with
updated last known alive date or death date based on data collected through April
2012.
Results: The table summarizes median OS, previously reported survival
rates at 1, 2, and 3 years, and current analyses for 4-year survival rates by treatment
group.
Table: 1127P
Treatment
group
Median OS,
months
[95% CI]
Overall survival rate, % [95% CI]
Conclusions: The 4-year survival rates observed in an extended follow-up of a
completed phase III trial suggests that IPI 10 mg/kg in combination with DTIC
continues to demonstrate a survival benefit compared to the control arm. The
continued survival of some patients at 4 yrs suggests that prolonged survival may
indeed be obtained in some pts with treatment-naive MM. This observation of
long-term survival benefit in a phase III RCT is consistent with observations from
phase I/II studies of IPI in patients with advanced melanoma.
Disclosure: M. Maio: Paid advisor in boards from BMS and Roche. C. Robert:
Consultant for BMS, GSK, Roche and Novartis. C. Garbe: I received honoraria and
research funding from BMS. S. Francis: Employed by BMS. K. Chin: Employed by
BMS and have Stock ownership. J. Wolchok: I am a consultant to BMS, Merck and
GSK. I receive rsearch funding from BMS. All other authors have declared no
conflicts of interest.
1128P THE EUROPEAN IPILIMUMAB EXPANDED ACCESS
PROGRAMME (EAP): EFFICACY AND SAFETY DATA FROM
THE ITALIAN COHORT OF PATIENTS WITH PRETREATED,
ADVANCED MELANOMA
P.A. Ascierto 1 , V. Chiarion Sileni 2 , M. Del Vecchio 3 , M. Altomonte 4 , F. De Galitiis 5 ,
L. Ridolfi 6 , F. Cognetti 7 , A. Testori 8 , M.G. Bernengo 9 , P. Queirolo 10
1 Unit of Medical Oncology and Innovative Therapy, Istituto Nazionale Tumori di
Napoli, Napoli, ITALY, 2 U.O. Oncologia Medica, Istituto Oncologico Veneto
IOV-IRCCS, Padova, ITALY, 3 Department of Medical Oncology, Fondazione
IRCCS Istituto Nazionale dei Tumori Milan, Milan, ITALY, 4 Department of
Oncology, Azienda Ospedaliera Senese - Medical Oncology and Immunotherapy
Unit, Siena, ITALY, 5 Department of Oncology, Dermopathic Institute of the
Immaculate IDI-IRCCS, Rome, ITALY, 6 Medical Oncology, Scientific Institute of
Romagna for the Study and Treatment of Cancer (IRST), Meldola, ITALY,
7 Division Medical Oncology A, Istituto Regina Elena, Roma, ITALY, 8 Melanoma
Division, Eurpean Institute of Oncology, Milan, ITALY, 9 Institute of Dermatology,
University Hospital St John the Baptist, Turin, ITALY, 10 National Institute for
Cancer Research, San Martino Hospital, Genoa, ITALY
Purpose: Ipilimumab was the first agent approved for the treatment of unresectable
or metastatic melanoma that showed an overall survival benefit in a randomised
phase III trial. Here, we evaluate the safety and efficacy of ipilimumab treatment
outside of clinical trials in patients enrolled in the EAP in Italy.
Methods: Ipilimumab was available upon physician request for patients aged ≥16
years with unresectable stage III/stage IV melanoma who had either failed systemic
therapy or were intolerant to ≥1 systemic treatment and for whom no other
therapeutic option was available. Ipilimumab 3 mg/kg was administered
intravenously every 3 weeks for 4 doses. Tumour assessments were conducted at
baseline and after completion of induction therapy using immune-related response
criteria. Patients were monitored for adverse events (AEs), including immune-related
AEs, within 3 to 4 days of each ipilimumab dose using Common Terminology
Criteria for Adverse Events v.3.0.
Results: In total, 848 Italian patients participated in the EAP from June 2010 to
April 2012 across 53 centres. Of these 848 patients, data are currently available for
563 patients. With a median follow-up of 3 months, the disease control rate among
468 evaluable patients was 31.4%, including 7 patients with a complete response, 51
with a partial response and 89 with stable disease. As of April 2012, median
progression-free survival and overall survival were 3.1 months and 6.2 months,
respectively, with 1-year survival rate of 34%. In total, 50.1% patients reported an AE
of any grade, most of which were drug-related (36.2%). Grade 3/4 AEs were reported
by 18.5% patients and considered drug-related in 8.5%. Eleven patients discontinued
treatment due to toxicity. AEs were generally reversible with treatment as per
protocol-specific guidelines. Complete data on all 848 patients, with longer
follow-up, will be presented.
Conclusions: Ipilimumab is a feasible treatment option for pretreated patients who
progressed on, or were unable to tolerate previous therapies. Many patients
experienced durable disease control.
Disclosure: P.A. Ascierto: PA has served as a consultant for Merck Sharp & Dohme,
and as an advisor to Bristol-Myers Squibb (BMS), Merck Sharp & Dohme, Roche,
GlaxoSmithKline, Amgen, Celgene, Medimmune and Novartis. He has received
honoraria from BMS, Merck Sharp & Dohme and Roche. V. Chiarion Sileni: Vanna
Chiaron Sileni has acted as an advisor for Bristol-Myers Squibb, Roche,
1-year 2-year 3-year 4-year
IPI + DTIC N = 250 11.2 [9.4-13.6] 47.5% [41.2–53.8] 28.8% [23.2–34.6] 21.2% [16.1–26.5] 19.0% [14.2 - 24.2]
Placebo + DTIC N = 252 9.1 [7.8-10.5] 36.4% [30.4–42.4] 17.8% [13.2–22.6] 12.1% [8.1–16.3] 9.6% [6.1 - 13.5]
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds404 | ix367