METex14 Patients See Improved Outcomes Following Savolitinib Treatment

Patients with non‒small cell lung cancer with undetectable circulating tumor MET Exon 14 (METex14) following treatment with savolitinib are more likely to have positive progression-free and overall survival outcomes.

According to data presented during the 2021 Virtual American Association for Cancer Research Annual Meeting, patients with non‒small cell lung cancer (NSCLC) with undetectable circulating tumor (ctDNA) MET Exon 14 (METex14) following treatment with savolitinib are more likely to have positive progression-free and overall survival outcomes.

“METex14 clearance upon savolitinib treatment was correlated with significantly longer progression-free survival [PFS] and overall survival [OS] compared with those who had detectable METex14,” said lead author Yongfeng Yu, MD, of the Shanghai Chest Hospital, Shanghai Jiao Tong University in Shanghai, China.

He cautioned the sample size was small and confirmation of the finding with a larger sample size was needed.

The median PFS for patients treated with savolitinib who had undetectable METex14 (n = 14) was 30.3 months (95% CI, 6.8-NC) with a hazard ratio (HR) of 0.72 (95% CI, 0.28-1.87; P = .501). The median OS for these patients was 35.8 months (95% CI, 14-NC) with an HR of 0.89 (95% CI, 0.25-3.18; P = .835).

For patients who had detectable METex14 following treatment (n = 10), the median PFS was 5.5 months (95% CI, 0.66-5.6) with an HR of 4.94 (95 CI, 1.83-13.36; P = .002). The median OS for these patients was 8.7 months (95% CI, 0.8-10.6). HR was 7.06 (95% CI, 2.39-20.89; P <.001).

For patients treated with savolitinib who were non-evaluable for METex14 (n = 22), the median PFS was 4.1 months (95% CI, 4.0-6.9). HR was 3.45 (95% CI, 1.48-8.03; P = .006). The median OS for these patients was 10.6 months (95% CI, 4.8-12.0). HR was 5.88 (95% CI, 2.24-15.47; P <.001).

METex14 was undectable for 20 patients at baseline. The median PFS for those patients was 13.8 months (95% CI, 4.2-22.1) and the median OS was not calculable.

Investigators also studied concurrent gene alterations with METex14 and noted alterations with likely resistance to savolitinib including KRAS, NRAS, PIK3CA, BRAF, FGF19 amplification, and others.

Savolitinib is a potent and selective MET tyrosine kinase inhibitor. The agent previously demonstrated clinical efficacy and a manageable safety profile in Chinese NSCLC patients with METex14 alterations in a phase 2 study (NCT02897479).

In the analysis presented at AACR, investigators studied ctDNA analysis of METex14 at baseline and clearance upon treatment using next generation sequencing, QIAamp Circulating Nucleic Acid Kit from Qiagen. They collected plasma samples pre-dose and at tumor assessment visits, until disease progression or end of treatment. Data cut-off was August 2020.