AT SSO 2015

HOUSTON (FRONTLINE MEDICAL NEWS)Newer systemic therapies for metastatic malignant melanoma have resulted in significant gains in survival, but at a cost that may be unsustainable in the near future, according to Dr. Jeffrey E. Gershenwald.

Up to one-half of all expenses related to the treatment of malignant melanoma are accounted for by the care of patients with advanced disease, yet patients with distant metastases (stage IV disease) account for only about 2% of all patients, said Dr. Gershenwald, professor of surgical oncology at the University of Texas M.D. Anderson Cancer Center, Houston.

“How best can we achieve the right therapy for the right patient at the right time, and as we learn more and more about some of the therapies, particularly in melanoma, for the right length of time? We can’t really afford to give treatments in perpetuity, so we need to know how long they actually need to be delivered in order to have optimal value for the patient,” he said at the annual Society of Surgical Oncology Cancer Symposium.

Over the last 3 decades, and particularly over the last 5 years, there have been tremendous forward strides in therapy. In 1975, when dacarbazine became the standard of care for metastatic melanoma, it was associated with response rates of only about 6%-15%, durable responses in only 5%-15% of patients, and a median overall survival of about 6-9 months, Dr. Gershenwald reported.

Treatment toxicities, but not response rates, increased with the introduction of interleukin-2 in 1998, which for want of a better drug became the new preferred treatment.

But with the introduction of new systemic therapies, such as immune checkpoint inhibitors (ipilimumab [Yervoy], nivolumab [Opdivo], and pembrolizumab [Keytruda]) and targeted agents (vemurafenib [Zelboraf], dabrafenib [Tafinlar], and trametinib [Mekinist]), response rates have soared, resulting in an improvement in 1-year survival rates from about 30% to 35% in 1970 to as high as 80% in clinical trials in 2014.

Increased survival, higher costs

Dr. Gershenwald pointed to a recently published cost-effectiveness analysis of treatment strategies for BRAF-mutated metastatic melanoma. In it, the authors noted that vemurafenib costs $13,000 per month, translating into $207,000 for a patient with median survival. Patients for whom vemurafenib fails are often put on ipilimumab, at $150,000 per course.

The authors calculated that the incremental cost-effectiveness ratio (ICER) for vemurafenib compared with dacarbazine was nearly $354,993 per quality-adjusted life-year (QALY) gained, a figure that is more than threefold higher than widely accepted thresholds for cost-effective treatment ($50,000-$100,000 per QALY gained).

The ICER for firstline vemurafenib followed by ipilimumab was $158,139, still well above the accepted limits.

The authors of the cost analysis noted that the treatments could become cost effective if drug prices were to drop significantly, or if clinical trials could establish whether it was possible to achieve a durable response without continued therapy.

Going forward, clinicians will need to consider disease burden, including both the extent and growth rate of the disease, as well as the risk of recurrence, in deciding whether to use adjuvant therapies, Dr. Gershenwald said.

In addition, clinical choices will be based on disease biology, predictors of response (although few such predictors currently exist), the likelihood of resistance, and drug toxicities, quality of life, and ease of administration, he said.

Dr. Gershenwald disclosed serving on a Merck advisory board.