Immunotherapy for RCC: Is it cost effective?
BY ALICIA GALLEGOS
For the treatment of renal cell carcinoma, immunotherapy with checkpoint inhibitors is now a major modality for advanced disease, both as an initial therapy and an after-antiangiogenic therapy for patients treated first with targeted agents. The U.S. Food and Drug Administration thus far has approved several immunotherapies for advanced kidney cancers, including, the anti–PD-1 checkpoint inhibitor nivolumab, the combination of nivolumab (Opdivo) and the anti-CTLA-4 checkpoint inhibitor ipilimumab (Yervoy), and the cytokine aldesleukin (Proleukin).
Although studies show the therapies are markedly effective for some patients, costs for the treatments are steep. The average cost of nivolumab in the treatment of advanced RCC for instance, is $101,070 per patient, according to a recent study (Eur Urol. 2017 Apr. doi: 10.1016/j.eururo.2017.07.041).
A cost analysis by Dr. McGregor presented at the 2017 Kidney Cancer Association meeting found the combination treatment of nivolumab and ipilimumab for patients with advanced RCC for 1 year would cost $213,500, excluding infusion costs.
For a combined regimen of nivolumab and ipilimumab in the treatment of metastatic melanoma, the cost is about $300,000 per patient, according to a cost analysis by Leonard Saltz, MD, of Memorial Sloan Kettering Cancer Center, New York, published in JAMA Oncology. Dr. Saltz determined that for the combined regimen, patients with a 20% copay would pay about $60,000 in annual out-of-pocket costs for the treatment (JAMA Oncol. 2016 Jan. doi: 10.1001/jamaoncol.2015.4191).
Since his analysis, presented at the 2015 American Society of Clinical Oncology meeting, the cost of immunotherapy has only risen, said Dr. Saltz, executive director for clinical value and sustainability and head of the colorectal oncology section at Memorial Sloan Kettering Cancer Center.
Are benefits worth high cost?
The research is clear that immunotherapy drugs are demonstrating value by generating longer life spans for cancer patients, said Daniel M. Geynisman, MD, an oncologist and researcher at Fox Chase Cancer Center Temple Health in Philadelphia.
Nivolumab, for instance, was shown to improve overall survival by a median of nearly 6 months when compared with the cancer drug everolimus in patients with advanced clear cell RCC who were previously treated, according to a study published in the New England Journal of Medicine (2015 Nov 5. doi: 10.1056/NEJMoa1510665). Adverse side effects were also lower. A more recent analysis in the New England Journal of Medicine found that overall survival and response rates were significantly higher with nivolumab plus ipilimumab, compared with sunitinib, among patients with previously untreated advanced RCC (N Engl J Med. 2018 Apr 5. doi: 10.1056/NEJMoa1712126). A phase II study presented at the 2018 Genitourinary Cancers Symposium meanwhile, showed that a combination of atezolizumab and bevacizumab led to longer progression-free survival rates for patients with advanced or metastatic RCC, compared with sunitinib, according to a 2018 summary of immunotherapy in RCC on UpToDate.com.
In the second study, published in Experimental Hematology & Oncology in 2018, findings showed nivolumab had a 92% probability of being cost effective versus everolimus at an $150,000 willingness-to-pay threshold. The study included costs associated with nivolumab acquisition, administration, monitoring, disease management, end of life care, and the management of adverse outcomes. Over a 25-year period, treatment with nivolumab resulted in an estimated quality-adjusted life-year (QALY) gain of about a year compared with treatment with everolimus (Exp Hematol Oncol. 2018 Feb 9. doi: 10.1186/s40164-018-0095-8).
“While the cost of the [immunotherapy drugs] may be more expensive, if [they] potentially cure our patients, it may minimize other costs associated with long-term disease morbidities: [For example,] hospitalizations due to complications from disease progression, interventions for pain, or other symptom control,” he said.
Big expense, deep impact
For patients with renal cell carcinoma, the high cost of immunotherapy treatment can inhibit their ability to pursue and pay for treatment, said Christopher S. Hollenbeak, PhD, a professor and head of the department of health policy and administration at Penn State University, Hershey. He led the 2011 Journal of Managed Care Pharmacy study on health care costs for RCC.
Dr. Geynisman adds that foundations and patient-assistant programs can greatly help patients with the cost of cancer treatments, but applying and reapplying for grants and awaiting approvals can be stressful. A 2018 study led by Dr. Geynisman found that, for oral anticancer medications for prostrate or kidney cancer, more than half of prescriptions were too expensive for patients to afford and required the acquisition of financial assistance.
“It can be a huge time burden and a financial burden for patients, and a psychological burden [in terms of] being worried about how to obtain these medications,” Dr. Geynisman said.
The high price for RCC immunotherapy drugs will likely start to taper off as time goes on, Mr. Hollenbeak said. He notes that the current prices result from a more challenging manufacturing process as well as freedom by patent holders to charge more in the initial marketing of their medications.
“The cost of immunotherapy for RCC is following the same trend for most new drugs and biologics,” Mr. Hollenbeak said in an interview. “They enter the market with a very high price tag, and over time, as alternatives emerge, the price begins to fall.”