How Immune Checkpoint Inhibitors Affect NTRK-Mutant NSCLC

Patients with NSCLC who have NTRK mutations have a survival advantage with immune checkpoint inhibitors compared with patients who have wild-type NTRK, according to a study conducted in China. These findings were especially true when taking into consideration tumor mutational burden (TMB) and blood TMB (bTMB).

Xiaoling Zhang and colleagues analyzed mutation frequency with clinical characteristics and patient survival in a cohort (n=1567) from the cBioPortal. Patients had NTRK1 mutation (3.5%), NTRK2 mutation (1.5%), or NTRK3 mutation (5.0%). They discovered that patients with an NTRK mutation had worse median OS than patients with wild-type NTRK (18.9 months vs 21.2 months, respectively).

“These findings suggested that patients with NTRK family mutations had worse prognosis compared [with wild-type] patients if not defining specific treatments,” the researchers said.

However, when treated with an immune checkpoint inhibitor, patients who were NTRK mutant versus wild-type lived longer. Zhang observed these data using two cohorts (Samstein [n=350]) and (OAK/POPLAR [n=569]).

Median OS was 21 months for NTRK mutant compared with 11 months for wild-type NTRK in the Samstein cohort. All patients had advanced NSCLC and 94% received anti-PD-1/PD-L1 monotherapy.

In the OAK-POPLAR cohort, identical median OS was detected between patients with an NTRK mutation and those who were wild-type (13.2 months vs 13.5 months, respectively). All patients were treated with atezolizumab (Tecentriq). Furthermore, while these patients had similar PD-L1 expression, the NTRK mutation group had higher TMB, bTMB, and enriched antitumor immunity.