NEW YORK – The UK's National Institute for Health and Care Excellence (NICE) has issued a new draft report recommending against the histology-independent use of larotrectinib (Bayer's Vitrakvi) for advanced adult and pediatric cancer patients treated through the National Health Service (NHS), even for rare cancer types or when no other satisfactory treatment options exist.
At the request of the UK's Department of Health and Social Care, NICE undertook an appraisal consultation on the use of larotrectinib — a drug that targets tumor specific fusions involving the tyrosine receptor kinase enzyme-coding gene NTRK. Under current conditional marketing authorization from the European Medicines Agency, larotrectinib can be used to treat NTRK fusion-positive solid tumors in adults or children with locally advanced, metastatic, or non-surgically resectable cancer cases without appropriate treatment alternatives.
Based on the drug's current price tag, coupled with input from Bayer, consultants outside the drug company, clinical and patient representatives, the national guidance group deemed that the drug didn't meet its cost-effective threshold for widespread use for histology- and primary tumor site-independent cancer treatment in the NHS system. It also recommended against including larotrectinib in the Cancer Drugs Fund.
The conclusion relied on an estimated monthly cost of £15,000 ($19,610) for larotrectinib before applying the UK's value-added tax, though the authors noted that Bayer "has a commercial arrangement which would have applied if the technology had been recommended."
Consequently, the report's authors suggested additional data will be needed before going forward with broader coverage of the drug in a histology-free setting. They noted, for instance, that the largest clinical trials of larotrectinib so far have focused on overall response rate, with immature progression-free or overall survival patterns. Â
However, the report's authors did not provide details on potential strategies or partnerships that would be used to access larotrectinib in the meantime.
"The committee understood that an important innovation was already underway as part of the NHS long-term plan to develop more sophisticated strategies to improve genomic testing in clinical practice," the NICE appraisal committee wrote in their report. "These advances will likely help the uptake of treatments targeted to a gene alteration."
For example, the NHS Genomic Medicine Service is expected to test as many as 100,000 solid tumors when it is up and running at full tilt in the next two years or so, according to data provided to NICE for the report. The national genomic testing service from NHS England is eventually intended to replace local testing centers with seven hubs for tumor profiling, though additional work is needed to refine the application of genomics in the clinical diagnostics setting.
"We're hopeful that further data collection, coupled with responsible pricing from the companies, will lead to progressive, new treatments like these being available to patients," Meindert Boysen, director of NICE's health technology center, said in a statement.
"As a partner in the Accelerated Access Collaborative [a healthcare innovation system with government, industry, and NHS representatives]," he added, "NICE will do all it can to assist the company in providing the reassurances required to allow larotrectinib to be recommended for inclusion in the [Cancer Drugs Fund]."
The organization emphasized that the current draft document does not represent the group's final larotrectinib guidance. NICE plans to have an appraisal committee meeting in March of this year, following a consultation period that is open to comment until early February.
Likewise, the authors noted that the current draft recommendation "is not intended to affect treatment with larotrectinib that was started in the NHS before this guidance was published."
"People having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published," they explained, "until they and their NHS clinician consider it appropriate to stop."
Earlier this week, NICE issued guidance recommending olaparib (Lynparza from AstraZeneca and Merck) use and Cancer Drug Fund inclusion for relapsed ovarian, fallopian tube, or primary peritoneal cancers in individuals with risky BRCA1/2 mutations. The organization's latest guidance around palbociclib (Pfizer's Ibrance) with fulvestrant (AstraZeneca's Faslodex) — also out earlier this week — recommended palbociclib-fulvestrant use within the Cancer Drug Fund for certain advanced HER-negative breast cancer patients, though authors of that report called current cost-effectiveness estimates around the treatment "very uncertain."
The organization has also been tasked with evaluating entrectinib (Rozlytrek from Roche- Genentech) in the histology-independent treatment setting in the UK and has said it will await preliminary European licensing decisions before sharing further guidance on that ROS1 mutation-targeting drug.
"[P]reparation continues for the introduction of this next generation of therapies, including constructive conversations with Roche on a commercial deal for entrectinib," John Stewart, national director of specialized commissioning for the NHS, said in a statement.