Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
TP53 mutations in EGFR mt+ NSCLC IV as a predictive factor for ORR, PFS, and OS irrespective of T790M.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20679)
Author(s): Julia Roeper, Anne Christina Lueers, Markus Falk, Markus Tiemann, Fabian Otto-Sobotka, Frank Griesinger; Pius Hospital Oldenburg/ University of Oldenburg, Oldenburg, Germany; Pius Hospital, Oldenburg, Germany; Hematopathology Hamburg, Hamburg, Germany; Carl von Ossietzky University Oldenburg, Oldenburg, Germany; Pius-Hospital, University Department Internal Medicine-Oncology, University of Oldenburg, Oldenburg, Germany
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. Methods: 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. Results: 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. Conclusions: 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.