Fig. 1: TP53 pathway disruption is associated with shorter progression-free survival and mixed clinical responses to TKI therapy.

a Bar chart showing the percentage of responding patients with homogenous (gray) or mixed (red) responses to treatment with erlotinib or chemotherapy. b Mixed responses in the RECIST database were analysed using response criteria defined by ref. ¹⁵. Patients with at least two lesions where one shrank by at least 30% were included in the analysis. The number of patients with homogenous responses are shown in black for patients receiving erlotinib. The different patterns of progression seen in patients with a mixed response are shown in red. c Kaplan–Meier survival analysis of patients with E (n = 35, yellow line) and EP tumors (n = 82, green line), in the AURA2, AURA3, and AURA phase II expansion cohort, demonstrating the difference in PFS after osimertinib treatment (Log-rank test (two-sided) p = 4e⁻⁰⁴, HR 0.36, CI: 0.20–0.65). d Bar chart of the proportion of Homogenous (yellow) and Mixed (green) responses to osimertinib in patients with E or EP tumors (p = 0.0106 two-sided Fisher’s exact test). e Bar chart of the proportion of patients with E or EP mutant tumours with new lesions during osimertinib treatment (p = 0.0846 two-sided Fisher’s exact test). f Individual first tumor response within six months on osimertinib treatment, presented as % change in CT-measured tumor length. Each x-axis tick represents one patient (n = 21, E group of patients with 127 lesions and n = 39, EP group of patients with 246 lesions in total). The dotted lines show the Reiter et al. criteria for response (−30%) and progression (10%), respectively. Gray dots and whiskers represent the median change in tumor size and variability around the median value using the median absolute deviation (MAD) for each patient. Boxes underneath the graph indicate the occurrences of new lesions (red box), and mixed responses of existing lesions, as defined by ref. ¹⁵ (gray box), and patients with mixed responses with or without the occurrences of new lesions (blue box). Source data are provided as a Source Data file.