Title: Mobocertinib for treating EGFR exon 20 insertion-positive advanced non-small-cell lung cancer after platinum-based chemotherapy [ID3984]
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. Up to 85% of lung cancers are non-small-cell lung cancers (NSCLC).[2]_x000D_ _x000D_ Most 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 3) or to other parts of the body (metastatic disease; stage 4), and usually cannot be surgically removed. In 2017, 34,591 of people diagnosed with lung cancer had NSCLC in England, Wales, Jersey and Guernsey.[3] For most 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 programmed death-ligand 1 [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. People with advanced NSCLC with EGFR Exon 20 insertions have poorer treatment outcomes with currently available therapies than people with wild-type (non-mutated) EGFR or other types of EGFR mutations. Unlike other EGFR mutations, Exon 20 insertions have been associated with resistance to EGFR tyrosine kinase inhibitors (TKIs).[5]_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 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 recommended 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 122)._x000D_ _x000D_ If the disease continues to worsen after chemotherapy, nintedanib with docetaxel or docetaxel monotherapy are treatment options (NICE technology appraisal 347 and NICE guideline 121 respectively). For adults with an EGFR-positive tumour that has progressed after chemotherapy, erlotinib is a treatment option (NICE technology appraisal 374), For adults with an EGFR-positive tumour who have had both chemotherapy and a targeted treatment:_x000D_ _x000D_ • atezolizumab is recommended as an option (NICE technology appraisal 520)_x000D_ _x000D_ • pembrolizumab is recommended as an option for PD-L1-positive tumours (NICE technology appraisal 428)._x000D_ _x000D_ Nivolumab is also recommended for PD-L1-positive tumours after chemotherapy (NICE technology appraisal 713)._x000D_ _x000D_ 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 August 2021._x000D_ _x000D_ 2. Types of lung cancer. Cancer Research UK. Accessed August 2021._x000D_ _x000D_ 3. NLCA annual report 2018. Accessed August 2021._x000D_ _x000D_ 4. Zhang, H. Osimertinib making a breakthrough in lung cancer targeted therapy. Onco Targets and Therapy. 2016; 9: 5489–5493. Accessed August 2021_x000D_ _x000D_ 5. Burnett, H et al. Epidemiological and clinical burden of EGFR Exon 20 insertion in advanced non-small cell lung cancer: A systematic literature review. PLoS ONE. 2021; 16(3). Accessed August 2021.

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

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