Scottish Medicines Consortium Approves Rybrevant Combination for First-Line EGFR Exon 20 Insertion NSCLC Treatment
Key Insights
The Scottish Medicines Consortium (search) has approved Rybrevant (amivantamab) in combination with carboplatin and pemetrexed as the first targeted therapy specifically for first-line treatment of advanced NSCLC with EGFR (search) exon 20 insertion mutations in Scotland.
The Phase 3 PAPILLON study demonstrated that the combination increased median progression-free survival by 4.7 months (11.4 vs 6.7 months) compared to chemotherapy alone, with a 73% objective response rate.
This approval addresses a significant unmet medical need for patients with EGFR (search) exon 20 insertion mutations, who represent 12% of all EGFR mutation-positive NSCLC cases and historically have limited treatment options.
The Scottish Medicines Consortium (search) (SMC) has approved Rybrevant (amivantamab) in combination with carboplatin and pemetrexed for use within NHS Scotland as a first-line treatment for adult patients with advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR (search)) exon 20 insertion mutations. This marks the first targeted therapy available in Scotland specifically approved as a first-line treatment for this uncommon subtype of lung cancer.
Addressing Critical Unmet Medical Need
Lung cancer is the third most common cancer in Scotland, with around 5,300 people diagnosed each year, and NSCLC accounts for 80-85 percent of all cases. EGFR (search) exon 20 insertion mutations are associated with poorer outcomes compared to other more common EGFR mutations and occur in an estimated 12 percent of all EGFR mutation-positive NSCLC cases. There has been a significant unmet need for new, targeted treatment options for this group of patients, whose cancer is often resistant to other NSCLC treatments.
"EGFR (search)+ UK is delighted that the Scottish Medicines Consortium (search) has approved amivantamab with chemotherapy for eligible patients in Scotland diagnosed with EGFR Exon 20 insertion mutations NSCLC," said Prof. Virginia Harrison, Research Trustee, EGFR+ UK. "This announcement marks a landmark moment for a group of patients who have long faced limited and often ineffective treatment options. Today's decision changes that. It gives eligible patients and families a treatment option that truly targets their cancer from day one."
Phase 3 PAPILLON Study Results
The SMC's recommendation is based on data from the Phase 3 PAPILLON study, a registrational, randomised, open-label, multicentre trial comparing amivantamab with chemotherapy (carboplatin and pemetrexed) versus chemotherapy alone in people with untreated, locally advanced or metastatic NSCLC with activating EGFR (search) exon 20 insertion mutations.
The study found that amivantamab with carboplatin and pemetrexed increased median progression-free survival (PFS) by blinded independent committee review – the study's primary endpoint – by 4.7 months (11.4 months versus 6.7 months) compared to carboplatin and pemetrexed alone (hazard ratio for disease progression or death, 0.40; 95 percent CI, 0.30 to 0.53; P<0.001). At 18 months, PFS was reported in 31 percent of the patients in the amivantamab-chemotherapy group and in 3 percent of those in the chemotherapy group.
An objective response (complete or partial response) was reported in 73 percent of the patients (95 percent CI, 65 to 80) in the amivantamab-chemotherapy group and in 47 percent (95 percent CI, 39 to 56) of those in the chemotherapy group (rate ratio, 1.50; 95 percent CI, 1.32 to 1.68; P<0.001).
Safety Profile
In the dataset of amivantamab in combination with carboplatin and pemetrexed (N=301), the most frequent adverse reactions in all grades were rash (83 percent), neutropenia (57 percent), nail toxicity (53 percent), infusion related reactions (IRR) (51 percent), fatigue (43 percent), stomatitis (39 percent), nausea (43 percent), thrombocytopenia (40 percent), constipation (40 percent), oedema (40 percent), decreased appetite (33 percent), hypoalbuminaemia (32 percent), alanine aminotransferase increased (26 percent), aspartate aminotransferase increased (23 percent), vomiting (22 percent), and hypokalaemia (20 percent).
Serious adverse reactions included rash (2.7 percent), venous thromboembolism (2.3 percent), thrombocytopenia (2.3 percent) and interstitial lung disease (ILD) (2.0 percent). Eight percent of patients discontinued amivantamab due to adverse reactions. The most frequent adverse reactions leading to treatment discontinuation were IRR (2.7 percent), rash (2.3 percent), ILD (2.3 percent), and nail toxicity (1.0 percent).
Clinical Impact and Access
"The approval is very welcome news and an important advance in the treatment of patients with lung cancer in Scotland. This is the first targeted therapy available in Scotland specifically approved as a first-line treatment for patients with this uncommon subtype of lung cancer, where treatment options until now have been quite limited," said Dr. Brian Clark, Consultant Clinical Oncologist in Scotland.
Amanda Cunnington, UK Senior Director of Patient Access, Johnson & Johnson Innovative Medicine, emphasized the significance of this approval: "The availability of targeted treatment options is crucial for people living with lung cancer driven by specific mutations. We are therefore delighted to have secured access for eligible patients in Scotland to a first-line treatment targeting EGFR (search) exon 20 insertion mutations, which will make a real difference to these patients' lives."
About Amivantamab
Amivantamab is a fully human bispecific antibody which targets both EGFR (search) and mesenchymal-epithelial transition (MET). This makes amivantamab the first bispecific antibody targeting tumours with activating and resistant EGFR mutations and MET mutations and amplifications, addressing two major mechanisms of resistance in NSCLC.