NICE approves oral drug VITRAKVI®▼(larotrectinib), the first histology-independent treatment to be made available in England, for children and adults with TRK fusion driven cancer

• Histology-independent cancer treatments are designed to treat tumours regardless of where the primary tumour originates in the body¹
• The treatment demonstrated clinical efficacy with an overall response rate (ORR) of 67% from the pooled primary analysis set, including primary CNS patients, in adult and paediatric patients with TRK fusion driven cancer¹
• Median time to first response in patients treated with larotrectinib was 1.81 months¹
• Clinically meaningful improvements in quality of life were reported by 60% of adult patients and 76% of paediatric patients²
• Larotrectinib is approved for the treatment of advanced neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours, in adult and paediatric patients if the disease is locally advanced, metastatic or surgery could cause severe health problems, and if they have no satisfactory treatment options³

Reading, 21^st April 2020 – Bayer announced today that VITRAKVI^® (larotrectinib) was recommended by the National Institute for Health and Care Excellence (NICE) for the treatment of advanced neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumours in adult and paediatric patients, if the disease is locally advanced, metastatic or surgery could cause severe health problems, and if they have no satisfactory treatment options.³ Bayer’s larotrectinib is the first histology-independent treatment to be made available for NHS patients in England through the Cancer Drugs Fund.

Larotrectinib, an oral TRK inhibitor, is a histology-independent treatment which can treat solid tumours that have an NTRK gene fusion regardless of where the primary tumour originates in the body.¹ TRK fusion driven cancers can occur all around the body,⁴ commonly in rare tumour types with potentially unsatisfactory treatment options, such as surgery, chemotherapy and radiotherapy.

“Bayer welcomes NICE’s recommendation for larotrectinib as it will allow clinicians, for the first time in England, the opportunity to offer adult and paediatric patients with TRK fusion driven cancer a therapy that targets the specific driver of their disease,” said Amanda Cunnington, Head of Patient Access at Bayer UK. “Bayer is proud to have worked collaboratively with NICE and NHS England throughout this appraisal process for a first-in-class treatment, providing TRK fusion driven cancer patients a new and potentially beneficial oral treatment option.”

“The health service and our society are facing considerable challenges with the coronavirus pandemic.  Whilst NICE is rightly focusing its efforts on rapid COVID-19 guidelines, we welcome the recommendation being communicated so that eligible patients can access this oral treatment without delay.”

NICE’s decision is based on the pooled clinical analysis of 102 patients (93 patients from the primary analysis population and an additional 9 patients with primary CNS tumours) across the Phase I trial of adult patients, the Phase II NAVIGATE trial in adult and adolescent patients and the Phase I/II paediatric SCOUT trial.³ Larotrectinib demonstrated clinical efficacy with an overall response rate (ORR) of 67% (95% CI: 57, 76) from the pooled primary analysis set, including primary CNS tumour patients, in adult and paediatric patients with TRK fusion driven cancer.¹ Results in the primary analysis population excluding primary CNS tumour patients demonstrated an ORR of 72% (95% CI: 62, 81).¹

The median time to first response in patients treated with larotrectinib was 1.81 months at the time of the primary analysis.¹ The median overall survival (mOS) had not been reached at time of analysis. Larotrectinib showed a generally manageable safety profile across ages and tumour types with the majority of adverse events (AEs) being grade 1 or 2 in severity.¹ The most common adverse events (≥ 20%) in order of decreasing frequency included fatigue (32%), increased ALT (31%), dizziness (30%), increased AST (29%), constipation (29%), nausea (26%), anaemia (24%), and vomiting (20%).¹ Reported grade 3 adverse events include anaemia, weight increased, fatigue, increased AST, dizziness, paraesthesia, nausea, myalgia, and leukocyte count decreased. All the reported grade 3 adverse reactions occurred in less than 5% of patients, with the exception of anaemia (7%).¹ Grade 4 was the highest reported grade for adverse reactions neutrophil count decreased (1.6%) and ALT increased (< 1%).¹ Only 3% of patients had to permanently stop therapy due to treatment-emergent adverse events.¹

Adult and paediatric patients with TRK fusion driven cancer treated with larotrectinib experienced clinically meaningful improvements in quality of life (QoL).² In two global, multi-centre clinical trials, 60% of adult patients reported an improvement in EORTC QLQ-C30 global health scores. For paediatric patients, 76% reported improvements in PedsQL total scores.²

Bradley Price, Policy and Public Affairs Manager at Sarcoma UK, said “Sarcoma UK welcomes today’s approval of larotrectinib. New histology-independent, genomic-driven treatments like this have the potential to treat tumours irrespective of where the cancer starts, which is so important for cancers like sarcomas which can develop in any part of the body.

We know too well just how difficult it can be to treat cancers like sarcoma through traditional therapies like surgery, radiotherapy and chemotherapy, and with novel treatments few and far between, larotrectinib is a welcome addition to the available therapies for sarcoma, as well as to treat other tumour types like lung and colorectal cancer.

Eligible patients, who may well have no other treatment options, will now have access to more personalised treatments which target genetic changes that cause many types of cancers to grow and spread.”

Histology-independent treatments have been called out by NHS England Chief Executive Simon Stevens at the 2019 NHS annual conference as a class of cancer medicines to be fast-tracked in a similar manner as CAR-T cell cancer therapies. Histology-independent treatments are therefore seen as a priority and the latest example of how the NHS is leading the way in genomic-led cancer care. Genomic testing is key to identifying patients who are most likely to benefit from targeted oncology treatments, such as larotrectinib if NTRK gene fusions are identified.^5,6

“With the introduction of the NHS Genomic Medicine Service, cancer patients in England should benefit from routine access to appropriate genomic testing allowing more precise diagnosis and access to histology independent therapies, such as larotrectinib, if NTRK gene fusion is indicated,” said Amanda Cunnington. “Bayer is fully committed to working closely with the NHS at national and local levels, including via the Accelerated Access Collaborative (AAC), to ensure access to NTRK gene fusion testing for all eligible NHS patients across the country in due course and actively supporting the effective implementation of the Genomic Medicine Service.”