Concomitant TP53 mutations with response to crizotinib treatment in patients with ALK-rearranged non-small-cell lung cancer

BackgroundTP53 mutations are the most prevalent mutations detected in non-small-cell lung cancer (NSCLC) and have been revealed as a negative prognostic biomarker of outcome. The impact of concomitant TP53 mutations in ALK-rearranged NSCLC remains uncertain. MethodsTumor samples from 64 ALK-rearranged NSCLC patients receiving crizotinib treatment were subjected to next-generation sequencing (NGS) to identify TP53 mutational status. The clinicopathologic features of the TP53 mutations and its impact on the effect of crizotinib treatment were analyzed. ResultsAmong the 64 ALK-rearranged patients, 15 (23.4%) patients showed a TP53 mutation. Of these, six cases had disruptive mutations and nine with nondisruptive mutations. The objective response rate (ORR) and disease control rate (DCR) for TP53 mutated patients were both significantly lower compared with those for TP53 wild-type patients (p=0.003 and 0.023, respectively). A significantly shorter progression-free survival (PFS) was found in TP53 mutated patients compared with TP53 wild-type patients (p=0.045). Nondisruptive TP53 mutations were associated with a shorter PFS in comparison with disruptive TP53 mutations in ALK-rearranged patients (p=0.069). When nondisruptive TP53 mutated patients were in comparison with TP53 wild-type patients, nondisruptive TP53 mutations were associated with a significant reduced PFS (p=0.003). ConclusionsTP53 mutations, especially nondisruptive mutations, negatively affected the response to crizotinib and correlated with shorter PFS in ALK-rearranged NSCLC patients.