Prognostic impact of TP53 mutations in metastatic non-squamous non-small-cell lung cancer.

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e21033 Background: TP53 is the most common mutated gene in lung cancer, with a wide range of different mutations. It is unclear whereas TP53 mutations impact the prognosis of patients treated in first-line for advanced or metastatic non-squamous non-small-cell lung cancer (nsNSCLC). Methods: In this retrospective study, we studied the hypothetical impact of TP53 mutations in patients treated in first-line for advanced or metastatic nsNSCLC on overall survival (OS) and progression-free survival (PFS). Secondary objectives were to explore OS and PFS according to treatment received among the two groups. Results: From January 1, 2018 to May 31, 2021, 222 patients were included, 129 in the mutTP53 groups and 93 in the wtTP53 group. Estimated median follow-up time was 26.4 months (95% CI, 24.5-33.5) for mutTP53 group and 24.2 months (95% CI, 20.3-27.5) for wtTP53 group. Median OS (mOS) was 17.5 months (95% CI, 11.3-21.5) in the mutTP53 and 9.5 months (95% CI, 7.3-13.4) in the wtTP53 group, with a significant difference ( p= 0.039). Median PFS was 6.19 months (95% CI, 5.3-7.39) in the mutTP53 and 3.16 months (95% CI, 2.26-5.23) in the wtTP53 group, with a significant difference ( p= 0.011). In multivariable analysis, after adjusting for confounders, the risk of death over the study period appears to be lower in the mutTP53 group than in the wtTP53 group, although this result is not significant (HR 0.74, 95% CI 0.51-1.07, p= 0.11). In subgroup analysis by treatment received (chemotherapy, immune checkpoint inhibitors (ICI) or combination), only patients in the mutTP53 group treated with ICI had a significant improvement in OS compared to patients in the wtTP53 group. The mOS was 24.7 (95% CI, 20.8-NR) vs 10.6 months (95% CI, 4.5-NR) (HR 0.30, 95% CI 0.14-0.64, p= 0.002) for ICI group, and mOS was 20.5 (95% CI, 8.8-NR) vs 16.8 months (95% CI, 8.1-NR) for combination group (HR 1.73; 95% CI, 0.61-4.91, p= 0.3). Conclusions: TP53 mutations is associated with a better OS and PFS than wtTP53 in patients treated with ICI, but we found no difference for patients treated with chemotherapy or combination of chemotherapy and ICI. WtTP53 patient had a short OS on ICI and improved when ICI is combined with chemotherapy. This study emphasizes the importance of evaluating in prospective study the prognostic and predictive role of TP53 mutations in advanced or metastatic nsNSCLC.