Savolitinib showed promising activity and had an acceptable safety profile in patients with pulmonary sarcomatoid carcinoma and other non-small cell lung cancer (NSCLC) subtypes positive for MET exon 14 (METex14) skipping alterations. The results from a multicentre, single-arm, open-label, phase II study performed in 32 hospitals in China were reported on 21 June 2021 in The Lancet Respiratory Medicine by Prof. Shun Lu of the Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University in Shanghai, China and colleagues.
Savolitinib is a selective MET tyrosine-kinase inhibitor. The investigators studied its activity and safety in patients with pulmonary sarcomatoid carcinoma and other METex14-positive NSCLC subtypes. Eligible patients were 18 years or older with locally advanced or metastatic METex14-positive pulmonary sarcomatoid carcinoma or other NSCLC subtypes. They had either presented with disease progression or toxicity intolerance towards one or more standard treatments or were deemed clinically unsuitable for standard treatment. The patients were also MET inhibitor-naive and had measurable disease.
The study participants received either 600 mg in case of body weight ≥50 kg or 400 mg in case of body weight <50 kg of oral savolitinib once daily until disease progression, death, intolerable toxicity, initiation of other antitumour therapy, non-compliance, patient withdrawal, or patient discontinuation. Radiographic tumour evaluation was done at baseline, every 6 weeks within 1 year of the first dose, and every 12 weeks thereafter.
The primary endpoint was objective response rate (ORR), defined as the proportion of patients with confirmed complete or partial responses by independent review committee (IRC) assessment. The primary endpoint was assessed in the tumour response evaluable set, which comprised all treated patients with a measurable lesion at baseline and at least one adequate scheduled post-baseline tumour assessment or the presence of radiological disease progression, with a sensitivity analysis done in the full analysis set, which comprised all patients who received at least one dose of savolitinib. Safety was also evaluated in the full analysis set.
In this study (NCT02897479), the recruitment is completed with treatment and follow-up still ongoing. From November 2016 to August 2020, 84 patients with METex14 skipping alterations were screened for eligibility. However, 70 patients were enrolled, received savolitinib, and comprised the full analysis set. The IRC-assessed tumour response evaluable set comprised 61 patients.
At a median follow-up of 17.6 months (interquartile range 14.2–24.4), the IRC-assessed ORR was 49.2% (36.1–62.3; 30 of 61 patients) in the tumour response evaluable set and 42.9% (95% confidence interval 31.1–55.3; 30 of 70 patients) in the full analysis set.
All 70 patients reported at least one treatment-related adverse event (TRAE). Grade 3 or more TRAE occurred in 32 (46%) patients, the most frequent of which were increased aspartate aminotransferase, increased alanine aminotransferase, and peripheral oedema.
Treatment-related serious adverse events occurred in 17 (24%) patients, the most common being abnormal hepatic function and hypersensitivity.
One death due to tumour lysis syndrome in a patient with pulmonary sarcomatoid carcinoma was assessed by the investigator as probably related to savolitinib.
The authors stated that based on the study results, savolitinib could be a novel treatment option in this patients population.
The study was funded by the Hutchison MediPharma and AstraZeneca.
Lu S, Fang J, Li X, et al. Once-daily savolitinib in Chinese patients with pulmonary sarcomatoid carcinomas and other non-small cell lung cancers harbouring MET exon 14 skipping alterations: a multicentre, single-arm, open-label, phase 2 study. The Lancet Respiratory Medicine; Published online 21 June 2021. DOI: https://doi.org/10.1016/S2213-2600(21)00084-9