Title: Amivantamab for treating EGFR Exon 20 insertion-positive non-small-cell lung cancer after platinum-based chemotherapy [ID3836]
Funder: Department of Health and Social Care

Abstract: Lung cancer is the third most common cancer and the most common cause of cancer death in the UK, accounting for 13% of all new cancer cases and 21% of all cancer deaths in 2017.[1] There are around 48,000 new lung cancer cases and 35,000 deaths from lung cancer in the UK every year. Around 85% of lung cancers are non-small-cell lung cancers (NSCLC).[2]_x000D_ _x000D_ The majority of lung cancers are diagnosed at an advanced stage, when the cancer has spread to lymph nodes and other organs in the chest (locally advanced disease; stage III) or to other parts of the body (metastatic disease; stage IV), and usually cannot be surgically removed. In 2017, 88% (34,591) of people diagnosed with lung cancer had NSCLC in England, Wales, Jersey and Guernsey[3]. For the majority of people with NSCLC, the aims of therapy are to prolong survival and improve quality of life. Treatment choices are influenced by the presence of biological markers (such as mutations in epidermal growth factor receptor-tyrosine kinase (EGFR-TK), anaplastic-lymphoma-kinase (ALK) or PD-L1 status), histology (squamous or non-squamous) and previous treatment experience._x000D_ _x000D_ An estimated 10% to 35% of people with NSCLC have mutations to the protein epidermal growth factor receptor (EGFR).[4] Exon 20 is part of the EGFR gene that can be mutated by an addition to the DNA sequence._x000D_ _x000D_ For people whose locally advanced or metastatic disease tests positive for the activating EGFR-TK mutation and who have not previously had treatment, NICE guidance recommends the tyrosine kinase inhibitors (TKIs) osimertinib, dacomitinib, afatinib, erlotinib, and gefitinib as treatment options (NICE technology appraisal guidance 654, 595, 310, 258, and 192 respectively)._x000D_ _x000D_ Following disease progression with a TKI, osimertinib is available for EGFR T790M mutation-positive disease (NICE technology appraisal 653). Otherwise, atezolizumab in combination and pemetrexed with carboplatin or other platinum doublet chemotherapy are treatment options (NICE technology appraisal 584 and NICE guideline 121)._x000D_ _x000D_ If disease continues to worsen after chemotherapy, atezolizumab, nintedanib with docetaxel or docetaxel monotherapy are treatment options (NICE technology appraisals 520, 347 and NICE guideline 121 respectively). Pembrolizumab and nivolumab (nivolumab is only available on the cancer drugs fund) are available for PD-L1 positive tumors (NICE technology appraisals 428, 484). There are currently no available therapies that specifically target EGFR Exon 20 insertion mutations._x000D_ _x000D_ References_x000D_ 1. Lung cancer incidence. Cancer Research UK. Accessed November 2020._x000D_ 2. Types of lung cancer. Cancer Research UK. Accessed November 2020._x000D_ 3. NLCA annual report 2018. Accessed November 2020._x000D_ 4. Osimertinib for EGFR-positive non-small cell lung cancer – adjuvant. NIHR Innovation Observatory Health Technology Briefing. November 2020.

Lay abstract: To appraise the clinical and cost effectiveness of amivantamab within its marketing authorisation for treating EGFR Exon 20 insertion-positive non-small-cell lung cancer.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: CANCER AND NEOPLASMS