**3. Results**

#### *3.1. Clinico-Pathologic and Molecular Features of Patients*

Patients characteristics, *EGFR* mutations, type of TKI received and *TP53* mutations are reported in Table 1. All 136 patients carried an *EGFR* mutation (exon 19 deletions 53.7%, exon 21 L858R 35.3%, other *EGFR* mutations 11.0%) and received a first line *EGFR*-TKI (36.7% Erlotinib, 5.1% Erlotinib plus bevacizumab, 30.9% gefitinib, 27.2% afatinib). Of the patients with available information on smoking habit, half were never smokers (50.8%), and half were former or current smokers (28.8% and 20.3%, respectively). We found *TP53* mutations in 42 (30.9%) of the 136 analyzed patients: 12 mutations were in exon 5 (28.6%), 6 in exon 6 (14.3%), 13 in exon 7 (31.0%) and 11 in exon 8 (26.2%). Following the classification of *TP53* mutations into disruptive and non-disruptive ones [6], 11 patients had a disruptive mutation whereas 31 had a non-disruptive one (26.2% and 73.8%, respectively).


**Table 1.** Demographic, clinicopathological and molecular characteristics of patients (*n* = 136).

† The sum does not add up to the total due to missing values. \* Of these patients, 7 received Erlotinib plus Bevacizumab as a first line therapy, as provided in the Beverly clinical trial.

While for patients with exon 19 deletion the three different TKIs were used in an almost similar proportion (32.9% patients received erlotinib, 30.1% gefitinib, and 37.0% afatinib), patients with a mutation in exon 21 L858R were predominantly treated with erlotinib or gefitinib (52.1% and 39.6% of the patients, respectively), and those with uncommon mutations received predominantly erlotinib or afatinib (53.3% and 40.0%, respectively, Table S1).

No statistically significant associations were observed between type of *TP53* mutation, type of *EGFR* mutation and patient characteristics (Table S2).

#### *3.2. Patients Outcome in Relation to EGFR Mutations*

Overall, ORR and DCR were 67.4%, and 89.3%, respectively. Considering the clinical responses by type of *EGFR* mutation, ORR was considerably higher in the subgroup of patients with exon 19 deletion (77.5%), with respect to patients with L585R mutation (55.3%), and the subgroup with other mutations (54.6%), *p* = 0.029. A higher percentage of long responders was observed in patients carrying exon 19 deletion (12.3%), with respect to patients with L858R point mutation (7.3%), or patients with the other *EGFR* mutations (6.6%), Table 2.


**Table 2.** Best clinical response according to *EGFR* mutations.

† The sum does not add up to the total due to missing values.

Median PFS and OS were 12.3 (95% CI: 9.9–13.8) and 27.3 (95% CI: 21.9–52.9) months, respectively. No statistically significant association between PFS, OS and type of *EGFR* mutations was found (*p* = 0.282 and *p* = 0.207, respectively).
