Advanced Melanoma Survival and Costs Differ in Treatment Combo and Sequence Comparison

Starting immunotherapy first-line for patients with melanoma containing BRAF mutations, followed by BRAF + MEK inhibitors, was associated with longer survival and lower costs compared with prescribing inhibitors first, a study suggests.

“With the availability of multiple, effective agents for this patient population, we need to identify the optimal sequencing of therapy,” says Ahmad Tarhini, MD, PhD, Director of the Melanoma and Skin Cancer Program and Director of the Center for Immuno-Oncology Research at Cleveland Clinic Cancer Center.

The longer survival benefit suggested in this analysis “seems to be driven by a longer treatment-free interval after patients respond to immunotherapy,” Dr. Tarhini says.

Overall, when it comes to treatment selection, “the most important factor is what is in the best interest of patients, including increased cancer control and survival,” he says. “However, when we have more than one option with similar outcomes, it may be important to investigate costs.”

Which combo wins the wallet?

In the absence of data from head-to-head comparisons of immunotherapy and BRAF/MEK inhibitors in melanoma, the researchers devised a matching adjusted indirect treatment comparison. They also estimated cost per life year of different treatment strategies over a patient’s lifetime. The safety and cost data for individual agents were obtained from published literature.

The analysis suggested that an initiating treatment sequence consisting of anti-DP1 + anti-CTL4A given first line, followed by BRAF + MEK in second line was cost-effective. Dr. Tarhini presented these results at the American Society of Clinical Oncology 2018 annual meeting in Chicago.

The BRAF + MEK combination was dabrafenib + trametinib. The anti-PD1 + anti-CTL4A combination was nivolumab + ipilimumab; and the anti-PD1 was nivolumab or pembrolizumab, for which the researchers assumed similar efficacy.

“When the benefits are similar, cost becomes an important factor — not just at the individual patient level but also at a healthcare system level,” Dr. Tarhini says. The cost-per-life-year calculation took into account estimated costs for the duration of treatment, adverse events and subsequent management costs for cancer progression — not just the cost of the therapies themselves. Interestingly, because of this comprehensive economic evaluation, monotherapy was not always less expensive than combination therapy.

Changes in practice? Not yet

“Despite our findings, I don’t believe this should change clinical practices at this point,” Dr. Tarhini says. “These data are hypothesis generating and could be biased by unknown and unaccounted for factors, and therefore require validation.” The treatment combinations investigated are being compared prospectively in a multicenter study (NCT02224781).

The current retrospective study findings add to previous work in this area by Dr. Tarhini and team that investigated a similar sequencing model in BRAF Wild-Type melanoma.