medwireNews: Phase 2 study results indicate that savolitinib has promising antitumor activity in Chinese patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations, including those with pulmonary sarcomatoid carcinoma.
“Our results support savolitinib monotherapy as a novel treatment option for this population” of patients who were MET inhibitor-naïve but had received at least one standard treatment, say Shun Lu (Shanghai Jiao Tong University, China) and fellow investigators.
The multicenter trial included 70 patients with pulmonary sarcomatoid carcinoma (36%) or other NSCLC subtypes, such as adenocarcinoma (57%), who received the oral selective MET–tyrosine kinase inhibitor at a daily dose of 400 or 600 mg, depending on bodyweight (<50 or ≥50 kg, respectively).
After 17.6 months of follow-up, the primary endpoint of objective response as assessed by an independent review committee (IRC) was achieved by 49.2% of the 61 patients with a measurable lesion at baseline and at least one subsequent assessment or radiologic progression who made up the tumor response evaluable population.
The objective response rate (ORR) as assessed by investigators was 53.2% in these patients, while in the total study cohort, the IRC- and investigator-assessed ORRs were 42.9% and 47.1%, respectively.
All the responses were partial, but the response rates were considered clinically meaningful as they exceeded the prespecified value of 30%, notes the team.
In the full analysis set, the IRC-assessed median time to response was 1.4 months, while the median duration of response was 8.3 months, which “suggests that the response to savolitinib treatment was durable and rapid,” say Lu and colleagues.
The disease control rate as assessed by the IRC was 83% and the median progression-free survival (PFS) was 6.8 months, with a 6-month PFS rate of 52%, and “[r]esults for the outcomes were generally consistent regardless of whether they were assessed by the investigators or the IRC,” comment the investigators.
They add that “[a] similar tumour response was observed regardless of pathological subtype and previous treatment.” For instance, the IRC-assessed ORR was 40.0% among patients with pulmonary sarcomatoid sarcoma and 44.4% among those with other NSCLC subtypes, while the respective median durations of response were 17.9 and 8.3 months, and the median PFS times were 5.5 and 6.9 months.
Moreover, “savolitinib had an acceptable safety profile, with no new safety signals being observed,” says the team.
Specifically, 46% of patients in the full study cohort had a grade 3 or higher treatment-related adverse event (AE), most commonly increased aspartate aminotransferase (13%), increased alanine aminotransferase (10%), and peripheral edema (9%). AEs led to dose interruptions in 31%, dose reductions in 44%, and treatment discontinuation in 20%.
“This study provides strong evidence that the novel, highly selective MET inhibitor, savolitinib, leads to favourable clinical outcomes in patients with NSCLC, including pulmonary sarcomatoid carcinoma,” conclude Lu et al in The Lancet Respiratory Medicine.
“These findings support the use of savolitinib for NSCLC with MET [exon 14] alterations, regardless of pathological subtype.”
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