Steve Cimino

Nivolumab plus ipilimumab was deemed cost effective compared with sunitinib in advanced renal cell carcinoma (RCC), according to an analysis published in The Oncologist.1

“Our analysis predicts the combination is likely to be considered cost effective in the United States,” said coauthor Michal Sarfaty, MD, the Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel, in an email interview with Cancer Therapy Advisor. “It has already been adopted by the National Comprehensive Cancer Network guidelines as the standard of care for first-line treatment in intermediate- to poor-risk metastatic kidney cancer patients.”

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Previous studies have shown significantly higher overall survival and objective response rates with the immunotherapy combination of nivolumab plus ipilimumab compared with the targeted therapy sunitinib in intermediate- and poor-risk groups.2 The current study sought to examine the cost effectiveness of these 2 drugs versus sunitinib for first-line treatment of advanced RCC.

Due to sunitinib returning a superior objective response rate and progression-free survival in an exploratory analysis of the favorable-risk RCC group, this group was not included in the full analysis.

To compare the 2 treatment approaches, Dr Sarfaty and his colleagues developed a Markov model that incorporated data from the CheckMate 214 trial of nivolumab plus ipilimumab versus sunitinib in previously untreated advanced RCC. 2 All patients in the model started at stable disease and either remained there or transitioned to progressive disease or death. The study’s primary outputs were cost and quality-adjusted life-years (QALYs), which were then used to calculate the incremental cost-effectiveness ratio (ICER).

The total cost-per-patient of nivolumab plus ipilimumab was found to be $292,308, compared with $169,287 for sunitinib. Nivolumab plus ipilimumab also generated a gain of 0.978 QALYs over sunitinib; this meant an estimated ICER for nivolumab plus ipilimumab of $125,739/QALY compared with sunitinib.

The willingness-to-pay (WTP) thresholds in the United States typically range from $100,000/QALY to $150,000/QALY for cancer drugs and from $50,000/QALY to $100,000/QALY for noncancer drugs,3 which puts the nivolumab plus ipilimumab combination on the high end of the pricing spectrum.

Another new immunotherapy combination — paclitaxel plus ramucirumab for second-line metastatic gastric cancer — has an estimated ICER of $1,000,000/QALY,4 making the nivolumab plus ipilimumab combination in RCC appear reasonably priced by comparison.

Limitations of the current study included the model’s reliance on patients enrolled in clinical trials as opposed to real-world data (the nivolumab and ipilimumab combination was only approved to treat kidney cancer in 2018, however). As a result, there is a lack of long-term survival information on nivolumab plus ipilimumab in RCC. Despite the fact that there is optimism about how well patients will respond to the immunotherapy combination, the coauthors noted that the data for the model “are an extrapolation, and limit our confidence in the results.”

Dr Sarfaty acknowledged an additional limitation: the combination’s toxicity profile, which makes the therapeutic combination more difficult to adopt in community practice settings. “This is indeed problematic,” he said, “as immune-related toxicity may appear in different ways and necessitate[s] prompt management. This requires the education of health care providers, patients, and their caregivers. In time, I believe providers will be able to manage these patients outside of large centers.”

In addition, sunitinib itself has been found to be cost effective in metastatic RCC compared with both sorafenib alone and the combination of bevacizumab plus IFN-α, comparing favorably with other newer treatments.5 But in an interview with Cancer Therapy Advisor, Hans Hammers, MD, PhD, of UT Southwestern Medical Center in Dallas, Texas, stated that while targeted therapies can potentially be cost effective, patient responses to these medications are typically not durable.

“Roughly 22% of patients on the nivolumab plus ipilimumab combination have to come off it because of side effects,” he said. “But we also know that these patients, even if they have to stop, can do just as well as those who continue therapy.”

He shared the story of a patient of his who was entered into the nivolumab plus ipilimumab clinical trial, received the combination, and developed an irreversible side effect after just one dose. His treatment was halted and he was only observed from there; his very aggressive kidney cancer, however, disappeared. He hasn’t needed additional therapy for going on approximately 4 years now.

“It’s like a leukemia model,” he added. “There is a lot of treatment and perhaps a lot of toxicity upfront, but if it works well, you may see a very durable benefit. You may even be able to stop therapy, which could mean costs coming down as well. ‘Cured’ is a strong word to use, but that may be where we’re headed.”


  1. Reinhorn D, Sarfaty M, Leshno M, et al. A cost‐effectiveness analysis of nivolumab and ipilimumab versus sunitinib in first‐line intermediate‐ to poor‐risk advanced renal cell carcinoma. The Oncologist. 2019;24(3):366–371.
  2. Motzer RJ, Tannir NM, McDermott DF, et al. Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma. N Engl J Med. 2018;378(14):1277–1290.
  3. Bae YH, Mullins CD. Do value thresholds for oncology drugs differ from nononcology drugs? J Manag Care Spec Pharm. 2014;20(11):1086–1092.
  4. Lam SW, Wai M, Lau JE, McNamara M, Earl M, Udeh B. Cost-effectiveness analysis of second-line chemotherapy agents for advanced gastric cancer. Pharmacother J Hum Pharmacol Drug Ther. 2017;37:94–103.
  5. Benedict A, Figlin RA, Sandström P, et al. Economic evaluation of new targeted therapies for the first-line treatment of patients with metastatic renal cell carcinoma. BJU Int. 2011;108(5):665–672.

This article originally appeared on Cancer Therapy Advisor