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Rescooped by veronica garay from Melanoma BRAF Inhibitors Review
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Treating Metastatic Melanoma in 2014: What Just Happened and What Is Next? | 2014 Educational Book | Meeting Library

Treating Metastatic Melanoma in 2014: What Just Happened and What Is Next? | 2014 Educational Book | Meeting Library | miscelaneas hepaticas | Scoop.it
Treating Metastatic Melanoma in 2014: What Just Happened and What Is Next?
- Invited Articles - 2014 ASCO Annual Meeting

Via Krishan Maggon
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Krishan Maggon 's curator insight, June 4, 2014 4:04 PM

Prof Paul B. Chapman, MD, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065; email:chapmanp@mskcc.org.


ASCO 50th Meeting

 

In treating patients with metastatic melanoma, the expectation has finally changed. Just 3 years ago, patients could only be offered chemotherapy and/or interleukin-2 (IL2). Ultimately, few patients benefited from that treatment, although, for reasons still not completely understood, there were occasional stunning successes. Now, seemingly all of a sudden, RAF inhibitors,1,2 ipilimumab,3,4 and soon anti-PD1 antibodies5,6 have led to the expectation that tumors will shrink and that patient's lives can be extended with treatment. At this point, one can even dare to consider the possibility of cure for metastatic melanoma.7 As chemotherapy has shifted to second-, third-, or even fourth-line therapy, the changes in treatment have been revolutionary, transformative and exciting. Of course the truth is that these great outcomes are still enjoyed by only a minority of our patients. This article summarizes what the next steps may be in order to see these outcomes affect a larger number of patients with metastatic melanoma.

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Astra Zeneca/Array Selumetinib Increases PFS modestly Against Metastatic Uveal Melanoma

Astra Zeneca/Array Selumetinib Increases PFS modestly Against Metastatic Uveal Melanoma | miscelaneas hepaticas | Scoop.it
Melanoma Eye Drug NEW YORK, NY — For the first time, a therapy has been found that can delay progression of metastatic uveal melanoma, a rare and deadly form of melanoma of the eye. Results from a multicenter clinical ...

Via Krishan Maggon
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Krishan Maggon 's curator insight, June 20, 2014 7:57 AM
Effect of Selumetinib vs Chemotherapy on Progression-Free Survival in Uveal MelanomaA Randomized Clinical TrialRichard D. Carvajal, MD1,2; Jeffrey A. Sosman, MD3; Jorge Fernando Quevedo, MD4; Mohammed M. Milhem, MD5; Anthony M. Joshua, MBBS, PhD6; Ragini R. Kudchadkar, MD7; Gerald P. Linette, MD, PhD8; Thomas F. Gajewski, MD, PhD9; Jose Lutzky, MD10; David H. Lawson, MD11; Christopher D. Lao, MD12; Patrick J. Flynn, MD13; Mark R. Albertini, MD14; Takami Sato, MD, PhD15; Karl Lewis, MD16; Austin Doyle, MD17; Kristin Ancell, MD3; Katherine S. Panageas, DrPH1; Mark Bluth, MD1; Cyrus Hedvat, MD, PhD1; Joseph Erinjeri, MD, PhD1; Grazia Ambrosini, PhD1; Brian Marr, MD1; David H. Abramson, MD1,2; Mark Andrew Dickson, MD1,2; Jedd D. Wolchok, MD, PhD1,2; Paul B. Chapman, MD1,2; Gary K. Schwartz, MD1,2[+] Author AffiliationsJAMA. 2014;311(23):2397-2405. doi:10.1001/jama.2014.6096.





One hundred one patients were randomized in a 1:1 ratio to receive selumetinib, 75 mg orally twice daily on a continual basis (n = 50), or chemotherapy (temozolomide, 150 mg/m2 orally daily for 5 of every 28 days, or dacarbazine, 1000 mg/m2 intravenously every 21 days [investigator choice]; n = 51) until disease progression, death, intolerable adverse effects, or withdrawal of consent. 

 

 

Median progression-free survival among patients randomized to chemotherapy was 7 weeks (95% CI, 4.3-8.4 weeks; median treatment duration, 8 weeks; interquartile range [IQR], 4.3-16 weeks) and among those randomized to selumetinib was 15.9 weeks (95% CI, 8.4-21.1 weeks; median treatment duration, 16.1 weeks; IQR, 8.1-25.3 weeks) (hazard ratio, 0.46; 95% CI, 0.30-0.71; P < .001). Median overall survival time was 9.1 months (95% CI, 6.1-11.1 months) with chemotherapy and 11.8 months (95% CI, 9.8-15.7 months) with selumetinib (hazard ratio, 0.66; 95% CI, 0.41-1.06; P = .09). No objective responses were observed with chemotherapy. Forty-nine percent of patients treated with selumetinib achieved tumor regression, with 14% achieving an objective radiographic response to therapy. Treatment-related adverse events were observed in 97% of patients treated with selumetinib, with 37% requiring at least 1 dose reduction.

Conclusions and Relevance  In this hypothesis-generating study of patients with advanced uveal melanoma, selumetinib compared with chemotherapy resulted in a modestly improved progression-free survival and response rate; however, no improvement in overall survival was observed. Improvement in clinical outcomes was accompanied by a high rate of adverse events.