CHICAGO -- The novel kinase inhibitor selumetinib may be the first treatment to shrink advanced uveal melanoma, based on phase II trial results.
Half of patients on selumetinib saw their tumor shrink at least somewhat compared with 11% on temozolomide (Temodar), a standard chemotherapy used for skin melanoma, Richard Carvajal, MD, of Memorial Sloan-Kettering Cancer Center in New York City, and colleagues found.
Fully 15% of patients had at least a 30% reduction in tumor volume on the novel drug compared with none on temozolomide, the researchers reported here at the American Society of Clinical Oncology meeting.
Progression-free survival was also 54% better with the agent than with temozolomide (16 versus 7 weeks, P=0.0003).
The novel kinase inhibitor could become a standard since there isn't one for uveal melanoma other than enrolling patients in clinical trials, Carvajal told reporters at a press briefing.
"This is the first time any systemic therapy has been shown to work in patients with ocular melanoma. This disease has been viewed as practically untreatable until now," commented Michael Atkins, MD, a melanoma specialist and deputy director of Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.
The results represent a breakthrough that could lead to further advances, Atkins said in an email to MedPage Today.
"This opens the door not only for treatment of patients with metastatic uveal melanoma, but also for testing more potent MEK inhibitors, MEK inhibitors-based combinations, and even testing MEK inhibitors in the adjuvant setting for patients with tumors containing high-risk features," he said.
Sapna Patel, MD, a melanoma oncologist at MD Anderson Cancer Center in Houston, wasn't so impressed by the response rate but agreed that it will spark a shift in options for patients who have had none.
"Although the response rate was quite small in a small fraction of patients, for the first time there is an effective therapy now for this disease and it's a starting off point now to consider combining this treatment with other treatments," she told MedPage Today.
Selumetinib blocks mitogen-activated protein (MAP), also known as extracellular signal-regulated kinases (ERK), which are together dubbed MEK. Genetic mutations in Gnaq and Gna11 activate that pathway to fuels cancer cell growth in more than 85% of ocular melanomas.
In the randomized trial, about 80% of the 98 metastatic uveal melanoma patients had one of the two mutations. The trial also included some wild-type gene patients but analyses yielded the same results including or excluding them.
Overall survival numerically favored twice-daily selumetinib at 75-mg but the difference wasn't significant compared with 150-mg/m2 temozolomide taken four times daily (mean 11 versus 9 months, P=0.4).
Carvajal suggested that the extensive crossover to selumetinib after disease progression in the control arm, about 80%, may have impacted that comparison.
No complete responses by RECIST criteria occurred.
Selumetinib is also being investigated as a treatment for cancers of the thyroid and lung, although with negative phase II results in endometrial cancer.
Another MEK inhibitor, trametinib (Mekinist), was approved on Wednesday for melanoma.
Physicians might generalize the results to the commercially available option, Patel suggested in an interview, but more study is needed, particularly in further honing the patient population who benefits, she noted.
"As with some of our past experiences, when the response rate is low we have to do better at identifying who is the patient that's going to respond," Patel said.
She cautioned that the one of the limitations of the current study was lack of tumor assessment at week 12; it's not clear if the patients on selumetinib actually progressed at week 12 rather than week 16. "If that is the case, then the magnitude of the benefit is reduced," she said.
The researchers reported no conflicts of interest.
Primary source: American Society of Clinical Oncology
Source reference:
Carvajal RD, et al. "Phase II study of selumetinib (sel) versus temozolomide (TMZ) in gnaq/Gna11 (Gq/11) mutant (mut) uveal melanoma" ASCO 2013.
Crystal Phend
Staff Writer
Crystal Phend joined MedPage Today in 2006 after roaming conference halls for publications including The Medical Post, Oncology Times, Doctor's Guide, and the journal IDrugs. When not covering medical meetings, she writes from Silicon Valley, just south of the San Francisco fog.
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