Background: Following
approval of ipilimumab, this observational cohort study (CA184-332) was
initiated to describe patient and disease characteristics, patterns of care,
survival, and adverse events (AEs) in advanced melanoma (AM) patients treated
with first-line ipilimumab in realworld US community practice. Methods: Adult
patients with treatment-naive AM who received ≥1 dose of ipilimumab 3 mg/kg between
April 2011 and September 2012 were retrospectively identified at US Oncology
sites. Clinical data were abstracted from patient medical records. Results:
Median age of the 157 patient cohorts was 66 years (range 21 - 91). 68.2% were
male, and 90.5% had a cutaneous primary site. At ipilimumab initiation, 80.9%
of patients had an ECOG performance status of 0 or 1; 54.1% were stage M1c;
34.4% had brain metastases; 24.8% had elevated lactate dehydrogenase, and 13.4%
were positive for BRAF mutation. All 4 cycles of ipilimumab were completed by
55.8% of patients. At a median follow-up of 8.5 months (range 2.9 - 15.0),
median overall survival was 11.5 months (95% CI: 8.9 - 16.6) and 1-year
survival was 46.7% (95% CI: 38.1 - 54.9). During ipilimumab treatment, AEs were
experienced by 63.7% of patients. The most frequent AEs were gastrointestinal
(41.4%; diarrhea in 19.1%) and skin-related (28.0%; rash in 17.8%); 17.8% of
patients had an AE that led to ipilimumab discontinuation. Conclusions: These
real-world results are consistent with those from clinical trials and provide
evidence supporting the effectiveness and safety of first-line ipilimumab 3
mg/kg monotherapy in patients with AM treated in a community practice setting.
References
[1]
American Cancer Society (2014) American Cancer Society: Cancer Facts & Figures 2014. American Cancer Society, Atlanta.
[2]
Surveillance Epidemiology and End Results: Cancer Statistics. http://seer.cancer.gov/statfacts/html/all.html
[3]
Korn, E.L., Liu, P.Y., Lee, S.J., Chapman, J.A., Niedzwiecki, D., Suman, V.J., et al. (2008) Meta-Analysis of Phase II Cooperative Group Trials in Metastatic Stage IV Melanoma to Determine Progression-Free and Overall Survival Benchmarks for Future Phase II Trials. Journal of Clinical Oncology, 26, 527-534.
http://dx.doi.org/10.1200/JCO.2007.12.7837
[4]
Garbe, C., Eigentler, T.K., Keilholz, U., Hauschild, A. and Kirkwood, J.M. (2011) Systematic Review of Medical Treatment in Melanoma: Current Status and Future Prospects. The Oncologist, 16, 5-24.
http://dx.doi.org/10.1634/theoncologist.2010-0190
[5]
Hodi, F.S., O’Day, S.J., McDermott, D.F., McDermott, D.F., Weber, R.W., Sosman, J.A., Haanen, J.B., et al. (2010) Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. New England Journal of Medicine, 363, 711-723. http://dx.doi.org/10.1056/NEJMoa1003466
[6]
Robert, C., Thomas, L., Bondarenko, I., O’Day, S., Weber, J., Garbe, C., et al. (2011) Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. New England Journal of Medicine, 364, 2517-2526.
http://dx.doi.org/10.1056/NEJMoa1104621
[7]
Chapman, P.B., Hauschild, A., Robert, C., Haanen, J.B., Ascierto, P., Larkin, J., et al. (2011) Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation. New England Journal of Medicine, 364, 2507-2516.
http://dx.doi.org/10.1056/NEJMoa1103782
[8]
Weber, J.S., Kahler, K.C. and Hauschild, A. (2012) Management of Immune-Related Adverse Events and Kinetics of Response with Ipilimumab. Journal of Clinical Oncology, 30, 2691-2697.
http://dx.doi.org/10.1200/JCO.2012.41.6750
[9]
Hersh, E.M., O’Day, S.J., Powderly, J., Khan, K.D., Pavlick, A.C., Cranmer, L.D., et al. (2011) A Phase II Multicenter Study of Ipilimumab with or without Dacarbazine in Chemotherapy-Na?ve Patients with Advanced Melanoma. Investigational New Drugs, 29, 489-498. http://dx.doi.org/10.1007/s10637-009-9376-8
[10]
Hamid, O., Schmidt, H., Nissan, A., Ridolfi, L., Aamdal, S., Hansson, J., et al. (2011) A Prospective Phase II Trial Exploring the Association between Tumor Microenvironment Biomarkers and Clinical Activity of Ipilimumab in Advanced Melanoma. Journal of Translational Medicine, 9, 204. http://dx.doi.org/10.1186/1479-5876-9-204
[11]
Schadendorf, D., Hodi, F.S., Robert, C., Weber, J.S., Margolin, K., Hamid, O., et al. (2013) Pooled Analysis of Long-Term Survival Data from Phase II and Phase III Trials of Ipilimumab in Metastatic or Locally Advanced, Unresectable Melanoma. European Cancer Congress 2013 (ECCO-ESMO-ESTRO), Amsterdam, 27 September-1 October 2013, Abstract LBA 24.
[12]
Damsky, W.E., Rosenbaum, L.E. and Bosenberg, M. (2010) Decoding Melanoma Metastasis. Cancers, 3, 126-163.
http://dx.doi.org/10.3390/cancers3010126
[13]
Margolin, K., Ernstoff, M.S., Hamid, O., Lawrence, D., McDermott, D., Puzanov, I., et al. (2012) Ipilimumab in Patients with Melanoma and Brain Metastases: An Open-Label, Phase 2 Trial. The Lancet Oncology, 13, 459-465.
http://dx.doi.org/10.1016/S1470-2045(12)70090-6
[14]
Di Giacomo, A.M., Ascierto, P.A., Pilla, L., Santinami, M., Ferrucci, P.F., Giannarelli, D., et al. (2012) Ipilimumab and Fotemustine in Patients with Advanced Melanoma (NIBIT M1): An Open-Label, Single-Arm Phase 2 Trial. The Lancet Oncology, 13, 879-886. http://dx.doi.org/10.1016/S1470-2045(12)70324-8
[15]
Jang, S. and Atkins, M.B. (2013) Which Drug, and When, for Patients with BRAF-Mutant Melanoma? The Lancet Oncology, 14, e60-e69. http://dx.doi.org/10.1016/S1470-2045(12)70539-9
[16]
Ackerman, A., Klein, O., McDermott, D.F., Wang, W., Ibrahim, N., Lawrence, D.P., et al. (2014) Outcomes of Patients with Metastatic Melanoma Treated with Immunotherapy Prior to or after BRAF Inhibitors. Cancer, 120, 1695-1701. http://dx.doi.org/10.1002/cncr.28620
[17]
Ascierto, P.A. and Margolin, K. (2014) Ipilimumab before BRAF Inhibitor Treatment May Be More Beneficial than Vice Versa for the Majority of Patients with Advanced Melanoma. Cancer, 120, 1617-1619.
http://dx.doi.org/10.1002/cncr.28622
[18]
Margolin, K.A., Wong, S.L., Penrod, J.R., Song, J., Chang, I.F., Johnson, D.B., et al. (2013) Effectiveness and Safety of First-Line Ipilimumab 3 mg/kg Therapy for Advanced Melanoma: Evidence from a US Multisite Retrospective Chart Review. European Cancer Congress 2013 (ECCO-ESMO-ESTRO), Amsterdam, 27 September-1 October 2013, Abstract 3742.