NICE Recommends Against Frontline Pembrolizumab/Axitinib in Advanced RCC

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has chosen to not recommend the combination of pembrolizumab (Keytruda) and axitinib (Inlyta) for use in treatment-naïve adult patients with advanced renal cell carcinoma (RCC).¹

When citing their reasoning, the agency explained that although clinical trial data indicate that the combination is more effective than sunitinib (Sutent) in this patient population, it is uncertain whether this regimen also results in long-term benefit; therefore, cost-effective estimates are also unclear.

“Uncertainties in the clinical evidence would not be resolved through data collection in the Cancers Drug Fund,” the committee wrote. “So, pembrolizumab with axitinib is not recommended for use in the fund.”

Moreover, the combination does not meet NICE’s criteria to be a life-extending treatment at end of life, as the most plausible cost-effective estimates are higher than what NICE typically considers as an acceptable use of National Health Service (NHS) resources, the agency stated in the appraisal consultation document.

The current list price of pembrolizumab is £2,630 ($3407.82) per 100 mg vial, and the cost of a single administration is £5,260 ($6815.64); this price represents about 3 weeks of treatment. Furthermore, the list price of axitinib is £3,517 ($4557.15) per 56 5-mg tablets, which represents approximately 28 days of treatment.

The agency stated that the decision is not intended to affect treatment with pembrolizumab plus axitinib that was started in the NHS before this guidance was published. Patients who are receiving treatment outside of this recommendation may continue without change to the funding arrangements in place for them prior to the publishing of this guidance, until they and their NHS clinician deem it appropriate to discontinue therapy.

In April 2019, the FDA approved the use of pembrolizumab plus axitinib for the frontline treatment of patients with advanced RCC. The approval was based on findings from the phase III KEYNOTE-426 trial, which showed that the regimen resulted in significantly improved overall response rates (ORRs), progression-free survival (PFS), and overall survival (OS) versus sunitinib in this patient population.

After a median follow-up of 12.8 months, the estimated percentage of patients who were alive at 12 months was 89.9% with pembrolizumab/axitinib versus 78.3% with sunitinib (HR, 0.53; 95% CI, 0.38-0.74; P <.0001).² The median PFS with the combination was 15.1 months compared with 11.1 months with sunitinib (HR, 0.69; 95% CI, 0.57-0.84; P <.001).

Furthermore, the ORR with pembrolizumab plus axitinib was 59.3% (95% CI, 54.5%-63.9%) versus 35.7% (95% CI, 31.1%-40.4%) with sunitinib (P <.001). Notably, benefit with the combination was reported across the International Metastatic Renal Cell Carcinoma Database Consortium risk groups, regardless of PD-L1 expression. A higher percentage of patients in the pembrolizumab/axitinib arm experienced grade ≥3 adverse events (AEs) than those in the sunitinib arm at 75.8% versus 70.6%, respectively.

The key clinical evidence reviewed by the NICE committee came from KEYNOTE-426. No evidence comparing the combination with either tivozanib (Fotivda) or pazopanib (Votrient) was provided; however, those 2 agents are considered to be as safe and effective as sunitinib, the agency stated.

“The committee concluded that pembrolizumab with axitinib was more effective than sunitinib for OS and PFS in untreated RCC, but the data are immature,” NICE stated in the appraisal consultation document.

In the United Kingdom, kidney cancer is estimated to account for about 4500 deaths annually, with 12,600 new cases reported every year. Eighty percent of those with kidney cancer have RCC, according to NICE.

“A patient expert explained that treatment with pembrolizumab with axitinib had been positive because their tumor had reduced and there were no notable [AEs] with the treatment, unlike their experience with other treatment options,” the committee wrote.

These patient experts also confirmed that those with RCC felt that AEs associated with treatment can significantly affect quality of life. Currently, a clear unmet need remains in the treatment of RCC, NICE stated.

“Overall, an option that improved survival and reduced [AEs] would be welcomed by patients and clinicians to allow more choice of treatment and individualized care plans,” the committee concluded.

References

1. Appraisal consultation document: pembrolizumab with axitinib for untreated advanced renal cell carcinoma. National Institute for Health and Care Excellence. Published February 2020. bit.ly/2HuQhy5. Accessed February 12, 2020.
2. Rini BI, Plimack ER, Stus V, et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1116-1127. doi: 10.1056/NEJMoa1816714.