NSCLC has to date a poor prognosis with life expectancy at five year of 26%. The development of precision medicine is going to improve the prognosis, but most of alterations are still lacking of clinical significance. Somatic BRCA alterations, is reported to be quite frequent in NSCLC, with a prevalence of 5.3-6.6%. However, no specific study to date specifically evaluated its prognostic and predictive role in this population of patients.
We evaluated BRCA status of aNSCLC patients undergone liquid biopsy at Istituto Nazionale dei Tumori in Milan and Luigi Vanvitelli Hospital in Naples. Guardant360CDx® was used and mutations pathogenicity were interpreted based on the COSMIC database. Only mutations interpreted as pathogenic were considered. Chi square and Fisher tests were used to match clinical characteristics with BRCA status and survival outcomes were analysed with Cox model.
307 patients had BRCA status available on liquid biopsy, of which 33 (10.7%) had a pathogenic mutation in BRCA1/2 genes. BRCAm patients were older, more frequently male and smoker, had a higher PS and higher PDL1 expression on tissue samples; however, none of these features was significantly associated except for PS. Among patients treated with first-line platinum-based CT, a trend for better PFS was observed among BRCAm patients vs wt, without reaching statistical significance (HR 0.76, CI 95% 0.43-1.35, p=0.354). An increased platinum ORR was observed in BRCA mut vs wt patients (47.6% vs 34.0%, p=0.012). Conversely, among patients treated with any-line IOT, a worse PFS was observed among BRCAm patients vs wt (mPFS 3.5 vs 7.2 m; HR 2.14, CI 95% 1.35-3.40; p=0.001) and numerically reduced ORR was also observed (13.0% vs 26.8%, p=0.192). Finally, BRCA mutations seem to do not have impact on OS (BRCAm vs wt: 28.2 vs 28.8 m; HR 1.17, CI 95% 0.76-1.79; p=0.482).
In our retrospective cohort of aNSCLC patients, presence of a pathogenic mutation in BRCA1/2 genes resulted in reduced benefit to IOT, without affecting overall survival, probably due of the counterbalance effect of the increased sensitivity to platinum-CT. These data could be used to guide therapeutic choices and therefore deserve to be confirmed in a prospective cohort.
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan.
Has not received any funding.
All authors have declared no conflicts of interest.