Targeted therapy in lung cancer—ASCO 2019 update

Abstract

Summary New targeted therapies for patients with non small cell lung cancer were presented at this year’s ASCO. EGFR exon 20 insertions might soon be treatable with TAK-788, which showed an objective response rate (ORR) of between 25 and 56% with a disease control rate (DCR) between 67 and 100% depending on the presence or absence of brain metastases at baseline. Capmatinib and tepotinib showed durable responses in MET exon 14 mutations as presented in the phase II GEOMETRY trial and the VISION trial. The median duration of response (DOR) was 9.7 months with a median progression free survival (PFS) of 5.42 months in pretreated patients and 11.14 months respective 9.6 months in those receiving capmatinib in the frontline setting. Tepotinib showed similar results with a median DOR of 12.4 months and a DCR of 66.7%. For RET-fusion lung cancer the well tolerated RET inhibitor BLU-667 has already been granted breakthrough therapy designation. Among previously treated patients an ORR of 58% and a DCR of 96% was reported. The median duration of response had not yet been reached, with many patients continuing to respond for longer than 24 months. For the large and hard-to-treat group of patients with KRAS-mutated lung cancer, early data on the covalent irreversible inhibitor of the KRASG12C-mutant kinase AMG 510 were presented. In pretreated patients AMG 510 achieved a 50% response rate, with a duration of treatment from 7.3 to 27.4 weeks. Furthermore, AMG 510 has been safe and well tolerated at dose levels tested in 35 patients in dose exploration.