Real-world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study

Mark R Middleton, Stéphane Dalle, Joel Claveau, Pilar Mut, Sigrun Hallmeyer, Patrice Plantin, Martin Highley, Srividya Kotapati, Trong Kim Le, Jane Brokaw, Amy P Abernethy, Mark R Middleton, Stéphane Dalle, Joel Claveau, Pilar Mut, Sigrun Hallmeyer, Patrice Plantin, Martin Highley, Srividya Kotapati, Trong Kim Le, Jane Brokaw, Amy P Abernethy

Abstract

The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had ≥1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies.

Keywords: Advanced melanoma; ipilimumab; observational study; real-world treatment practice; retrospective.

© 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Progression‐free survival (PFS) at 1‐year study follow‐up. (A) Overall study group (N = 177). (B) European cohort (n = 122). (C) North American cohort (n = 55).
Figure 2
Figure 2
Overall survival (OS) at 1‐year study follow‐up. (A) Overall study group (N = 177). (B) European cohort (n = 122). (C) North American cohort (n = 55). NA (not available) indicates that the upper limit corresponding to 95% CI for median upper limit boundary did not intersect with the survival probability equal to 0.5.

References

    1. Garbe, C. , Eigentler T. K., Keilholz U., Hauschild A., Kirkwood J. M.. 2011. Systematic review of medical treatment in melanoma: current status and future prospects. Oncologist 16:5–24.
    1. American Cancer Society 2015 . Melanoma skin cancer. Available at: (accessed 13 May 2015).
    1. Lens, M. B. , and Dawes M.. 2004. Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma. Br. J. Dermatol. 150:179–185.
    1. Jemal, A. , Saraiya M., Patel P., Cherala S. S., Barnholtz‐Sloan J., Kim J. et al. 2011. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992‐2006. J. Am. Acad. Dermatol. 65(Suppl. 1):S17–S25.
    1. American Cancer Society 2014 . Cancer facts & figures 2014. Available at: (accessed 13 May 2015).
    1. Ferlay, J. , Soerjomataram I., Ervik M., Eser S., Mathers C., Rebelo M. et al. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136:359–386.
    1. Michielin, O. , and Hoeller C.. 2015. Gaining momentum: new options and opportunities for the treatment of advanced melanoma. Cancer Treat. Rev. 41:660–670.
    1. Hodi, F. S. , O'Day S. J., McDermott D. F., Weber R. W., Sosman J. A., Haanen J. B., et al. 2010. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363:711–723.
    1. Robert, C. , Thomas L., Bondarenko I., O'Day S., Weber J., Garbe C., et al. 2011. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N. Engl. J. Med. 364:2517–2526.
    1. Chapman, P. B. , Hauschild A., Robert C., Haanen J. B., Ascierto P., Larkin J., et al.; BRIM‐3 Study Group . 2011. Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364:2507–2516.
    1. Hauschild, A. , Grob J. J., Demidov L. V., Jouary T., Gutzmer R., Millward M. et al. 2012. Dabrafenib in BRAF‐mutated metastatic melanoma: a multicentre, open‐label, phase 3 randomised controlled trial. Lancet 380:358–365.
    1. Flaherty, K. T. , Robert C., Hersey P., Nathan P., Garbe C., Milhem M., et al.; METRIC Study Group . 2012. Improved survival with MEK inhibition in BRAF‐mutated melanoma. N. Engl. J. Med. 367:107–114.
    1. Robert, C. , Long G. V., Brady B., Dutriaux C., Maio M., Mortier L., et al. 2015. Nivolumab in previously untreated melanoma without BRAF mutation. N. Engl. J. Med. 372:320–330.
    1. Robert, C. , Schachter J., Long G. V., Arance A., Grob J. J., Mortier L., et al.; KEYNOTE‐006 investigators . 2015. Pembrolizumab versus ipilimumab in advanced melanoma. N. Engl. J. Med. 372:2521–2532.
    1. OPDIVO® (nivolumab) [package insert] . 2016. Bristol‐Myers Squibb Company, Princeton, NJ.
    1. KEYTRUDA® (pembrolizumab) [package insert] . 2015. Merck & Co., Inc, Whitehouse Station, NJ.
    1. Lebbé, C. , Lorigan P., Ascierto P., Testori A., Bédane C., Middleton M., et al.; MELODY Study Group . 2012. Treatment patterns and outcomes among patients diagnosed with unresectable stage III or IV melanoma in Europe: a retrospective, longitudinal survey (MELODY study). Eur. J. Cancer 48:3205–3214.
    1. Zhao, Z. , Wang S., and Barber B. L.. 2014. Treatment patterns in patients with metastatic melanoma: a retrospective analysis. J. Skin Cancer 2014:371326.
    1. Avril, M. F. , Aamdal S., Grob J. J., Hauschild A., Mohr P., Bonerandi J. J., et al. 2004. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J. Clin. Oncol. 22:1118–1125.
    1. Bedikian, A. Y. , Millward M., Pehamberger H., Conry R., Gore M., Trefzer U., et al.; Oblimersen Melanoma Study Group . 2006. Bcl‐2 antisense (oblimersen sodium) plus dacarbazine in patients with advanced melanoma: the Oblimersen Melanoma Study Group. J. Clin. Oncol. 24:4738–4745.
    1. Schadendorf, D. , Ugurel S., Schuler‐Thurner B., Nestle F. O., Enk A., Bröcker E. B., et al.; DC Study Group of the DeCOG . 2006. Dacarbazine (DTIC) versus vaccination with autologous peptide‐pulsed dendritic cells (DC) in first‐line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann. Oncol. 17:563–570.
    1. Walker, M. S. , Reyes C., Kerr J., Satram‐Hoang S., and Stepanski E. J.. 2014. Treatment patterns and outcomes among patients with metastatic melanoma treated in community practice. Int. J. Dermatol. 53:499–506.

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