Nivolumab Plus Ipilimumab or Pembrolizumab Most Cost-Effective for Newly Diagnosed Advanced Melanoma

By Marilynn Larkin

August 03, 2020

NEW YORK (Reuters Health) - First-line treatment with nivolumab plus ipilimumab or pembrolizumab were the more cost-effective options for newly diagnosed advanced melanoma with unknown BRAF pathogenic variant status, a cost-utility analysis reveals.

BRAF and MEK inhibitors might be used in a second-line setting after BRAF pathogenic variant is confirmed.

"Economic evaluation is an important part of the value framework for cancer treatment," coauthors Dr. Lizheng Shi of Tulane University School of Public Health and Tropical Medicine in New Orleans and Dr. Bin Wu of Shanghai Jiaotong University told Reuters Health by email.

"Although (this) economic evaluation is mostly relevant to the US," they said, "our findings have implications globally because BRAF mutation testing may not be widely available in other countries due to social, technological, and capacity restrictions."

"The use of nivolumab plus ipilimumab could be recommended upfront across the commonly used treatment strategies," they note, "especially when the mutation status is not clear for newly diagnosed patients with advanced melanoma."

Drs. Shi and Wu compared the cost-utility of various immune checkpoint inhibitors and BRAF and MEK inhibitors using data from four large trials and from literature on cost and health preferences. Costs were estimated from the U.S. payer perspective.

All patients received one of eight frontline interventions: (1) ipilimumab; (2) nivolumab; (3) nivolumab plus ipilimumab; (4) pembrolizumab every three weeks; or BRAF pathogenic variant testing followed by (5) nivolumab for BRAF wild-type tumor or nivolumab plus ipilimumab for BRAF pathogenic variant; (6) pembrolizumab every three weeks for wild-type tumor and dabrafenib plus trametinib for pathogenic variant; (7) nivolumab for wild-type tumor and dabrafenib plus trametinib for pathogenic variant; or (8) pembrolizumab every three weeks for wild-type tumor and nivolumab plus ipilimumab for pathogenic variant.

As reported in JAMA Dermatology, nivolumab plus ipilimumab without BRAF pathogenic variant testing yielded the most significant health outcome, and nivolumab was the least expensive option.

The nivolumab, pembrolizumab, and nivolumab plus ipilimumab strategies were most cost-effective, with incremental cost-utility ratios of $8,593/QALY for pembrolizumab versus nivolumab and $125,593/QALY for nivolumab plus ipilimumab versus pembrolizumab.

BRAF pathogenic variant testing did not improve cost effectiveness or generate more favorable health outcomes in BRAF-guided strategies.

The authors note, "The most influential parameters driving our model were the treatment efficacy of these new regimens. The results indicated that those with longer overall survival would have more favorable economic outcomes."

Dr. Joseph Skitzki, Chair of the Melanoma/Sarcoma Disease Site Research Group at Roswell Park Comprehensive Cancer Center in Buffalo said the study "makes an important contribution in identifying strategies that have the most patient benefit and lowest cost, as the current economics of small molecule inhibitors and immunotherapies for melanoma are becoming unsustainable."

"But it's also important to look at individual practice patterns," he told Reuters Health by email. "It can be effective to initiate BRAF/MEK inhibitors in mutation-positive patients with rapidly progressive disease, for example, to gain control and then allow them to transition to a more durable immunotherapy."

"The patient's age and risk of toxicity are also key factors that would be difficult to account for in this study," he noted. "The cost of side-effects is also likely underestimated by this study, as BRAF/MEK inhibition toxicities are often limited and usually stop with cessation of treatment, as compared to immunotherapies, which can be life-long, profound, and expensive despite terminating therapy."

"It is also unclear whether BRAF mutation-carrying patients who benefit from immunotherapy or BRAF/MEK inhibition would have responded from either approach," he said. "It is possible that these patient groups are divergent and that clinical decisions based on economics could be harmful."

More information is needed on factors such as dosing schedules, levels of immunotherapy agents, extended treatment schedules and triplet therapies in trial (BRAF/MEK in combination with immunotherapy as front-line treatment), he added. "All of (these) may have a direct influence on the economic/patient benefit analyses."

"The take-home message of this study is a valuable one," Dr. Skitzki concluded: "Current treatments for metastatic melanoma are effective but incredibly expensive, and strategies to safely optimize care and reduce cost are warranted, but may be incredibly complex."

SOURCE: JAMA Dermatology, online July 22, 2020.