The impact of TP53 co-mutations and immunologic microenvironment on outcome of lung cancer with EGFR exon 20 insertions
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
Background: EGFR exon20 insertions (ex20ins) are targeted by novel compounds in non-small-cell lung cancer (NSCLC). However, data about outcome under conventional therapies and the influence of molecular features are scarce. Patients and methods: We retrospectively analysed 118 patients with evaluation of radiologic response based on RECIST v1.1. TP53 status was available for 88 cases. Results: Platinum doublets and chemoimmunotherapy showed similar response rates (20–25%), disease control rates (80%) and median progression-free survival (mPFS, ≈7 months), which were longer compared to monochemotherapy (9%, 59%, 4.1 months), EGFR inhibitors (0%, 46%, 3.0) and PD-(L)1 inhibitors (0%, 30%, 2.1; p < 0.05). Overall survival (OS) was not dependent on the choice of first-line treatment, but related to more lines of systemic therapy (p < 0.05). TP53 mutations and brain metastases were associated with shorter PFS under platinum doublets and EGFR inhibitors (HR 3.3–6.1, p < 0.01), and shorter OS for patients receiving both treatments (p < 0.05). More tumour CD8+ and less Th1 cells were associated with longer OS independent of brain and TP53 status (p < 0.01). No difference in outcome was noted according to the ex20ins site and use of pemetrexed (vs. other cytotoxics) or bevacizumab. Long-lasting responses (>1 year) occasionally occurred under EGFR inhibitors for both ‘near-’ and ‘far-loop’ variants. Conclusions: Platinum doublets and chemoimmunotherapy have the highest activity with ORR of 20–25% and mPFS of approximately 7 months, regardless of the cytotoxic partner, while PD-(L)1 inhibitors show limited efficacy. TP53 mutations, brain metastases and a lower tumour CD8/Th1-cell ratio are independently associated with shorter survival.
Details
Original language | English |
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Pages (from-to) | 106-118 |
Number of pages | 13 |
Journal | European journal of cancer |
Volume | 170 |
Publication status | Published - Jul 2022 |
Peer-reviewed | Yes |
External IDs
Scopus | 85130327475 |
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Keywords
Sustainable Development Goals
ASJC Scopus subject areas
Keywords
- Brain metastases, CD8 cells, EGFR NSCLC, EGFR exon 20, Immunologic tumour microenvironment, Overall survival, TP53 mutation, Th1 cells, Treatment failure