NICE Recommends Cancer Drugs Enzalutamide and Ipilimumab

The latest National Institute of Health and Care Excellence recommendations hail new drug options for prostate cancer and skin cancer

medwireNews: The National Institute of Health and Care Excellence (NICE) has issued guidance recommending the use of enzalutamide for metastatic hormone-relapsed prostate cancer and ipilimumab for untreated advanced melanoma.

The key clinical evidence leading to the approval of enzalutamide, an oral androgen receptor signalling inhibitor that reduces the proliferation of prostate cancer cells, arose from the AFFIRM trial. The participants received one or two courses of cytotoxic chemotherapy, at least one of which comprised docetaxel. The patients were then randomly assigned to receive enzalutamide (160 mg orally once a day) or placebo. Both groups also received best supportive care.

After a median follow-up of 15 months, 43% of 800 patients receiving enzalutamide had died, compared with 58% of 399 patients assigned to placebo. Median survival was extended by 4.5 months with enzalutamide, with the risk of death reduced by 38%. The drug was associated with fewer adverse events, although it did increase the risk of seizures compared with placebo.

Enzalutamide was also compared indirectly with abiraterone, but there was no significant difference in survival between the two treatment regimens.

The NICE guidance therefore recommends the use of enzalutamide for patients with metastatic prostate cancer that has relapsed following docetaxel-containing chemotherapy but not in those who have previously been treated with abiraterone. The recommended dose is 160 mg/day until disease progression.

The clinical evidence for ipilimumab, which blocks cytotoxic T-lymphocyte antigen 4 activity resulting in augmentation and prolongation of the T-cell immune response, came primarily from four randomised controlled trials (CA184-024, MDX010-08, BREAK-3 and BRIM-3).

In CA184-024, the median overall survival gain with ipilimumab (10 mg/kg) when taken with dacarbazine (850 mg/m2) was 2.1 months (hazard ratio [HR]=0.72), compared with dacarbazine alone, and in MDX010-08, at respective doses of 3 mg/kg and 1000 mg/m2, it was 2.9 months (HR=0.75).

The BRIM-3 and BREAK-3 trials were presented as indirect comparisons of ipilimumab with the B-Raf inhibitors vemurafenib and dabrafenib.

Ipilimumab plus dacarbazine significantly reduced the risk of death by 28%, compared with dacarbazine alone, but there was no significant difference in survival when ipilimumab plus dacarbazine was compared with vemurafenib or dabrafenib.

The recommended dose of ipilimumab for patients with previously untreated unresectable or metastatic melanoma is 3 mg/kg of body weight administered intravenously over a 90-minute period every 3 weeks for a total of four doses.

The use of both drugs within the National Health Service will be offered under patient access schemes, for which confidential discounts to the list price will be pre-agreed between the manufacturer and the Department of Health in England.

The cost of enzalutamide per quality adjusted life year gained would remain below 30,000 GBP. For ipilimumab it would be 47,900 GBP compared with dacarbazine and 28,600 GBP compared with vemurafenib.

Both drugs have already received US Food and Drug Administration approval; in 2012 for enzalutamide and 2011 for ipilimumab.

References

NICE Guidance: Enzalutamide for metastatic hormone‑relapsed prostate cancer previously treated with a docetaxel‑containing regimen. Page visited last time 28 July 2014.

NICE Guidance: Ipilimumab for previously untreated advanced (unresectable or metastatic) melanoma. Page visited last time 28 July 2014.

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