Survival outcomes and treatment patterns in patients with NFE2L2 and/or KEAP1 mutation-positive advanced squamous cell NSCLC using a real-world clinico-genomic database Journal Article
| Authors: | Wu, Y.; Yin, Y.; Crossland, V.; Vincent, S.; Paik, P. K.; Lineberry, N.; Faller, D. V. |
| Article Title: | Survival outcomes and treatment patterns in patients with NFE2L2 and/or KEAP1 mutation-positive advanced squamous cell NSCLC using a real-world clinico-genomic database |
| Abstract: | Background: NFE2L2 and/or KEAP1 mutations are associated with worse prognosis in all non-small cell lung cancer (NSCLC). We determined real-world survival outcomes and treatment patterns among patients with advanced squamous cell NSCLC by NFE2L2 and KEAP1 mutation status. Patients and Methods: A retrospective study (January 2011-December 2018) was conducted using a de-identified US-based clinico-genomic database. Adult patients with advanced squamous cell NSCLC with ≥ 2 in-network visits and comprehensive genomic profiling during the study period were included. Outcomes included real-world progression free survival (rwPFS) by line of therapy and overall survival (OS). The real-world effectiveness of anti-PD-1/PD-L1 first-line therapy was also evaluated in patients with a NFE2L2 and/or KEAP1 mutation. Results: Of 703 patients included (median age: 70.0 years), 31.6% had a NFE2L2 and/or KEAP1 mutation. The most common first- and second-line treatments regardless of mutation status were platinum-based chemotherapies and anti-PD-1/PD-L1 therapies. The most common third-line treatment was anti-PD-1/PD-L1 therapy in patients with a NFE2L2 and/or KEAP1 mutation and single-agent chemotherapy in patients with wild-type disease. Patients with a NFE2L2 and/or KEAP1 mutation versus wild-type disease had significantly shorter rwPFS (4.54 vs. 6.25 months; P =.003) following first- but not second- or third-line therapy and shorter median OS (13.59 vs. 17.37 months; P =.4105). No survival differences were observed in patients with a NFE2L2 and/or KEAP1 mutation receiving first-line anti-PD-1/PD-L1 therapies versus other therapies. Conclusions: Patients with advanced squamous cell NSCLC with a NFE2L2 and/or KEAP1 mutation have poor real-world survival, highlighting the need for a genotype-directed therapeutic strategy in this population. © 2022 |
| Keywords: | adult; aged; retrospective studies; genetics; mutation; squamous cell carcinoma; carcinoma, squamous cell; metabolism; carcinoma, non-small-cell lung; lung neoplasms; retrospective study; lung tumor; epithelium cell; epithelial cells; genomics; non-small cell lung cancer; programmed death 1 ligand 1; non small cell lung cancer; transcription factor nrf2; retrospective; kelch like ech associated protein 1; humans; human; b7-h1 antigen; nfe2l2 protein, human; nf-e2-related factor 2; kelch-like ech-associated protein 1; kelch-like ech-associated protein 1 gene mutation; nuclear factor erythroid 2 like 2 gene mutation; pd-1/pd-l1 therapy; keap1 protein, human |
| Journal Title: | Clinical Lung Cancer |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 1525-7304 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2022-09-01 |
| Start Page: | 487 |
| End Page: | 497 |
| Language: | English |
| DOI: | 10.1016/j.cllc.2022.05.008 |
| PUBMED: | 35705448 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 October 2022 -- Source: Scopus |
