ASCO 2012, Melanoma, New Drugs for Melanoma|June 3, 2012 9:52 pm

ASCO 2012 Melanoma Posters


This post will cover both the “discussed” posters, generally felt to be more important by ASCO organizers, and the “general” posters.

Instead of going through all the posters, I have selected the ones I found most interesting:

A phase II single arm study of pazopanib and paclitaxel as first-line treatment for unresectable stage III and stage IV melanoma: Interim analysis.

This is an early report of a study combining “metronomic” taxol (every week x 3 then off one week) with pazopanib, a drug that inhibits several receptors associated with metastatic spread and vascular supply, i.e. angiogenesis. Pazopanib, or Votrient, is already approved for treatment of renal cell carcinoma. Although the study continues, this interim update shows a response rate (complete and partial) of 42% with a disease control rate (including stable disease) in 21/24 patients or 87.5%. It also reminds us that some cytotoxic chemotherapy drugs, like taxol, do have activity against melanoma. Going forward, this drug should not be ignored when new combinations, particularly with targeted agents, are being considered and tested.

Safety and efficacy of MET inhibitor tivantinib (ARQ 197) combined with sorafenib in patients (pts) with NRAS wild-type or mutant melanoma from a phase I study.

Another early report, this time looking at the combination of Sorafenib, one of the first tyrosine kinase inhibitors tested, and a MET inhibitor called tivantinib or ARQ 197. This is a Phase I dose finding study and only 17 melanoma patients were treated. However, there were some dramatic responses and overall there was a 25% response rate and a 44% disease control rate. However, what makes this trial particularly interesting is that MET inhibitors are postulated to potentially be effective against melanomas with the NRAS mutation at the Q61 locus or location. This NRAS mutation appears to be the second most common mutation in melanomas, after the BRAF mutation. The “race” is on to try and identify ways of counteracting this mutation given the ongoing successes in addressing BRAF alterations. In this study, the small group of known NRAS mutant melanomas had a virtually doubled median PFS of 9.2 months.

Activity of cabozantinib (XL184) in metastatic melanoma: Results from a phase II randomized discontinuation trial (RDT).

This is an early study of XL184 or cabozantinib, another MET inhibitor that also has anti-VEGFR2 (anti-angiogenesis) properties. This study interestingly included patients with uveal melanoma, not just skin melanoma. The study design complicates the interpretation of the data somewhat however there was clearly activity against both skin and uveal melanoma, with an estimated 6 month PFS of 44% and significant response rates for both skin (60%) and uveal (48%) melanoma. There was no mention of NRAS mutation rates, so the potential influence of this variable is unknown.

Clinical activity and safety of combination therapy with temsirolimus and bevacizumab for advanced melanoma:  Phase II trial with correlative studies.

 Another combination study, this one with an mTOR inhibitor approved for renal cell carcinoma (temsirolimus or Torisel) and bevacizumab or Avastin. Like other studies above, it combines anti-cell-growth effects from the Torisel with anti-angiogenesis effects from the Avastin. What makes this study really interesting is the subgroup of patients who are wild-type for BRAF, i.e. do not have the BRAF mutation that allows therapy with specific inhibitors like Zelboraf. In this small subgroup, 10/10 patients had either a partial response or stable disease, for a disease control rate of 100% (!). Since at least 50% of patients do not have a BRAF mutation in their melanoma, the identification of additional potential treatment options, beyond immunotherapy, for this group is particularly exciting.
From the General Poster session, the posters were generally less interesting. There remains some question over the accuracy of the currently approved BRAF mutation detection test, and there is an ongoing search for new prognostic genetic tests. There were ongoing trials of interest using ipilimumab and vemurabinib in combination and also vemurafenib with a PI3k inhibitor. There was also a small retrospective study where ipilimumab showed some activity against uveal melanoma.
Finally, the electronic-only poster files had one study looking at survival for CLL patients who then developed melanoma, by
Eric Whitman, MD
Senior Editor, TheMelanomaCenter.com

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