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Huina Wang
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-45 - Clinico-Molecular Characteristics and Prognostic Outcomes of TP53 Mutated Patients with Advanced Non-Small Cell Lung Cancer (ID 679)
10:15 - 18:15 | Author(s): Huina Wang
- Abstract
Background
TP53 mutations are the most common molecular alterations in non-small cell lung cancer (NSCLC), but prognostic role of these mutations remains elusive. The aim of this study was to analyze the clinical and molecular characteristics of TP53 mutated NSCLC patients and to evaluate a novel approach called evolutionary action (EAp53) to stratify them into high-risk or low-risk groups.
Method
85 advanced NSCLC patients were enrolled. Variations of TP53 and other oncogenic drivers in NSCLC were identified by next-generation sequencing. EAp53 are available at http://mammoth.bcm.tmc.edu/EAp53/.
Result
Overall, 77 patients (90.6%) exhibited at least one genetic alteration. TP53 mutations were detected in 51 patients (60.0%) mainly in exons 4, 5, 6, 7, and 8. Notably, TP53 mutations were not observed in exon 4 when they coexisted with EGFR mutations. Mutant allele frequencies (MAFs) of EGFR sensitizing mutations (exon 19 deletion or L858R) were significantly higher than those of other EGFR mutations in patients harboring TP53 mutations (p = 0.012). Among TP53 mutated patients, 39.2% of them carried TP53 truncating mutations (nonsense, splice site, or frameshift), which were correlated with female gender and smokers (p = 0.026 and p = 0.024, respectively), and were potentially associated with young patients (p = 0.078), and were more common in non-DNA-binding domain of TP53 (p = 0.033). Additionally, overall survival time of 37 patients were collected, and patients with high-risk mutations stratified by EAp53 had a significantly worse OS compared to others (HR 23.15; 95% CI 4.30-124.50; p < 0.001).
Conclusion
This study is of great significance in understanding the population characteristics of TP53 mutated NSCLC patients. Furthermore, the data also indicates that evolutionary high risk TP53 mutations can identify a subset of patients with poor prognosis, suggesting that EAp53 is a novel approach and may be useful in clinical prognosis of NSCLC patients with TP53 mutations.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-42 - Emergence of CCDC6-RET Fusion with Maintained EGFR T790M Mutation After Resistance to Osimertinib in NSCLC: A Case Report (ID 1086)
10:15 - 18:15 | Author(s): Huina Wang
- Abstract
Background
First- and second-generation EGFR-TKIs have been widely used for advanced patients with EGFR mutation-positive non-small cell lung cancer (NSCLC); however, acquired resistance to these inhibitors, such as EGFR T790M mutation, could be present in resistant cases. Several third-generation EGFR-TKIs including osimertinib, have been explored and approved for conquering this resistance, whereas acquired resistance to osimertinib is evident and resistance mechanisms remain complex and incompletely elucidated.
Method
A 56-year-old never-smoking Asian woman presenting with back and groin pain for 2 years, and was diagnosed with stage IV lung adenocarcinoma with multiple lung, liver, brain and bone metastases in February 2015. The patient carried EGFR exon 19 deletion and clinically responded to initial erlotinib treatment, who progressed on erlotinib after 20 months, and a T790M mutation was detected by next-generation sequencing (NGS). Osimertinib treatment was administrated for 13 months during which time the patient remained stable according to the Response Evaluation Criteria in Solid Tumors. The patient progressed with bone metastases in January 2018 and no other mutations were detected by NGS, who then started the treatment with osimertinib, bevacizumab, and complementary radiation therapy. However, the patient discontinued the treatment due to the progress with bilateral lung nodules. In order to probe into the subsequent therapy, circulating tumor DNA (ctDNA) was analyzed using NGS with Acornmed Panel in August 2018.
Result
The genomic profile of the tumor disclosed actionable mutations including EGFR exon 19 deletion, EGFR T790M mutation, and CCDC6-RET fusion. Osimertinib and bevacizumab discontinued because of the rapid progress, serious adverse effects of gradeⅡsuppression of bone marrow, and shortness of breath. Based on the molecular test results, the patient received treatment with cabozantinib and osimertinib in October 2018, which also failed to slow down the progress of the disease. Further ctDNA test in November 2018 showed EGFR exon 19 deletion, EGFR T790M mutation, and CCDC6-RET fusion were identified again; however, no novel mutations were detected. Unfortunately, the symptoms worsened quickly and the patient died of respiratory failure in December 2018.
Conclusion
The specifc mechanisms of acquiring drug resistance for EGFR-TKIs have not been fully elucidated. Based on ctDNA-based NGS, we reported a case maintained EGFR T790M mutation and acquired CCDC6-RET fusion after resistance to osimertinib, which was rare since acquired RET fusion was only found in EGFR T790M lost patients. More studies about the mechanism should be explored to lead to effective treatment strategies in this population.
