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Markus Falk
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-26 - TP53 Mutations in EGFR mt+ NSCLC IV: Strong Independent Predictive Factor for ORR, PFS and OS Irrespective of T790M (Now Available) (ID 2566)
09:45 - 18:00 | Author(s): Markus Falk
- Abstract
Background
The impact of TP53 mutations in EGFR mt+ pts on PFS and OS is controversial, and different classifications of TP53 mt+ with respect to functional and potential predictive impact have been published. Therefore, we retrospectively analyzed the impact of TP53 aberrations on ORR, PFS and OS in a cohort of EGFR mt+ NSCLC IV pts (UICC 7) using different classifications of TP53 mutations.
Method
75 EGFR mt+ NSCLC IV pts were analyzed for TP53 co-mutations. TP53 mt+ were classified according to Poeta et al. into (1) disruptive vs. non-disruptive, according to structural prediction and biophysical characteristics into (2) pathogenic vs. non-pathogenic and finally into (3) exon 8 vs. non-exon 8 mutations according to Crino et al.. The endpoints ORR according to Recist 1.1, PFS and OS were calculated by Kaplan Meier.
Result
69 of the 75 EGFR mt+ pts (92%) had a common mutation in EGFR E19/21. In 59/75 pts (79%) material was sufficient for successful TP53 analysis. TP53 mt+ were found in 29/59 pts (49%), 16/59 (27%) had a TP53 disruptive mt+, 13/59 (22%) a TP53 non-disruptive mt+ and 30/59 a TP53 WT configuration. Using the structural/biophysical classification, 7/59 (12%) had a TP53 non-pathogenic and 22/59 (37%) a TP53 pathogenic mt+. Of the 29 mutated pts, 6 had a TP53 Exon 8 mt+. Median PFS on 1st line TKI was 12 vs. 18 months for non-disruptive/disruptive mt+ vs. WT (p<0.004), 11 vs. 17 months for pathogenic vs. non-pathogenic/WT (p<0.0001), and 7 vs. 12 vs. 18 months for exon 8 vs. non-exon 8 vs. WT (p<0.006). Median OS was 24 vs. 42 months in non-disruptive/disruptive mt+ vs. WT (p<0.0009), 23 vs. 42 months in pathogenic vs. non-pathogenic/WT (p<0.001) and 12 vs. 28 months for TP53 exon 8 vs. non-exon 8 mt+ (p<0.024). Additionally ORR was significantly impacted by TP53 mt+. In rebiopsy samples on acquired resistance, no new TP53 mutations were observed and there were no correlations of TP53 mutations with clinical factors and the EGFR mt+ type including T790M.
Conclusion
TP53 seems to be a frequent co-mutation in EGFR mt+ NSCLC and has a strong impact on all clinical endpoints on TKI therapy. These data might have an impact on the management and follow up of pts with TP53 mt+. Furthermore, there is an urgent need for further therapeutic approaches in this patient group.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-63 - Evaluation of Combined Biomarkers for Tumor Response to Immunotherapy (I/O) in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) (Now Available) (ID 1708)
10:15 - 18:15 | Author(s): Markus Falk
- Abstract
Background
Immune checkpoint inhibitors have revolutionized NSCLC treatment. At present, the only established predictive biomarker for I/O-therapy stratification are PD-L1 expression and MSI status. However, the expression of PD-L1 is limited by heterogeneous expression and even high expressors not always respond to I/O therapy. The aim of the study is to evaluate the value of combinations of positive (Tumor Mutational Burden, PD-L1) and negative (a.o. CD73 expression and inactivating STK11 mutations) predictive markers in patients (pts) with advanced NSCLC on I/O therapy.
Method
A retrospective study was performed on a cohort of 54 pts with advanced NSCLC that have been treated with I/O between 2015 and 2018. Pts were selected by the availability of tumor tissue and based on tumor response evaluated by RECIST v1.1 criteria: only patients with durable tumor response (CR,PR > 6 months) and patients with no tumor response (PD as best response) were analyzed for biomarkers: hybrid capture NGS assay for TMB (New Oncology) including STK11 mutations and IHC tests for PD-L1, CD73 and VISTA. Adjusted Cox regression and ROC analysis will be performed to evaluate the predictive value of the different biomarkers.
Result
43/54 pts received nivolumab, 11/54 pembrolizumab in different therapy lines (from 1st to 5th line). 24 pts were defined as having a durable tumor response (median PFS 20 months, median OS not reached) 30 pts as primary progressors (median PFS 2 months, p<0.0001), median OS 12 months, p<0.0001). In 30/54 pts enough material was available for TMB testing. The median TMB-value is 11.42 mutations/Mb. In 13 durable responders median TMB-value was 13.28 mutations/Mb versus 11.00 mutations/Mb in 17 primary non-responders. STK11 mutations were observed in 3/17 primary non-responders (10%) vs. 0/13 in durable responders (0%). Additional analyses of PD-L1, CD73, and VISTA will be presented at the meeting as well as correlative data of the parameters analysed.
Conclusion
Our results suggest that integrating several biomarkers including positive and negative predictive markers may correlate better with responses to I/O than PD-L1 and TMB alone.
