Larotrectinib Approved in UK for NTRK+ Cancers

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with advanced NTRK fusion—positive solid tumors. The treatment will now be available in the UK through the National Health Service (NHS).¹

“Histology independent medicines, like larotrectinib, are an exciting new development in the treatment of cancer. These cutting-edge therapies can be used to treat tumours with often rare genetic mutations regardless of where in the body the tumour originated. The clinical evidence is usually based on extremely small sample sizes, requiring novel approaches to testing them in clinical trials and translation into models of assessment for potential value in NHS practice,” Meindert Boysen, deputy chief executive and director of the Centre for Health Technology Evaluation at NICE, said in a press release.

“We’re therefore pleased to be able to recommend larotrectinib for use in the Cancer Drugs Fund while more data is collected on its clinical effectiveness, and we recognise the contribution of our appraisal committee, the company and other stakeholders,” added Boysen.

Larotrectinib was granted an accelerated approval for this indication by the US FDA in November 2018 based on data from 3 multicenter, open-label, single-arm clinical trials: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

In 55 evaluable patients, larotrectinib was found to induce an overall response rate (ORR) of 75% (95% CI, 61%-85%) per independent review and 80% (95% CI, 67%-90%) via investigator assessment, according to data published in the New England Journal of Medicine in February 2018.² Furthermore, 13% (n =7) of patients experienced a complete response (CR) with the agent, 62% (n = 34) had a partial response, and 13% (n = 7) had stable disease.

At a median follow-up of 8.3 months, the median duration not response (DOR) had not been reached. At a median follow-up of 9.9 months, median progression-free survival (PFS) had also not been reached. At 1 year, investigators reported that the majority of responses (71%) were ongoing, and more than half of patients (55%) remained free of disease progression.

In updated data from the integrated analysis of the 3 trials presented at the 2019 ESMO Congress, larotrectinib induced an ORR of 79% of 153 evaluable patients across several tumor types (95% CI, 72%-85%).³ CRs were observed in 16% (n = 24) of patients and partial responses noted in 63% (n = 97) of patients. With an additional 12% of patients achieving stable disease at best response, the clinical benefit rate with the agent was 91%.

Furthermore, in the primary cohort of 55 patients, the median DOR with larotrectinib in 44 patients with CRs or PRS at a median follow-up of 26 months was 35.2 months (95% CI, 21.2-not evaluable [NE]). Median PFS in the primary cohort was 25.8 months (95% CI, 9.9-NE); 27 patients experienced disease progression.

“While NHS staff are working around the clock to deal with the global coronavirus pandemic, the NHS is also working hard to make sure that the best care is available for other patients. Cancer treatment must be a priority, and that will be advanced by the first in a new generation of drugs that can cure previously untreatable tumours,” Simon Stevens, NHS chief executive, stated in the press release.

“This exciting new breakthrough in cancer treatment is the latest example of how the NHS leads the way in the new era of personalised cancer care, even when pulling out all the stops to respond to coronavirus. The benefits for patients, in particular children, of being able to treat many different types of cancers with one drug is potentially huge, helping them to lead longer, healthier lives,” added Stevens.

References

1. NHS strikes deal on first in a new generation of cancer busting drugs. Posted April 22, 2020. https://bit.ly/3eL68HS. Accessed April 22, 2020.
2. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378(8):731-739. doi: 10.1056/NEJMoa1714448.
3. Hyman DM, van Tilburg CM, Albert CM, et al. Durability of response with larotrectinib in adult and pediatric patients with TRK fusion cancer. Ann Oncol. 2019;30(suppl 5; abstr 445PD). doi: 10.1093/annonc/mdz244.007.