Genetic testing in NSCLC could increase benefits of targeted therapy
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Among patients with non-small cell lung cancer who harbor MET exon 14 skipping mutations, or METex14+, savolitinib demonstrated tolerability and anti-tumor activity, according to findings from a phase 2 study presented at the virtual ASCO annual meeting.
“The most important takeaway for physicians is to test patients with non-small cell lung cancer for genetic mutations, because there might be a targeted therapy that will benefit those patients more than non-targeted options,” Shun Lu, MD, PhD, professor at the Shanghai Chest Hospital, Jiao Tong University, told Healio. “It is estimated that 2% to 3% of NSCLC patients have MET exon 14 skipping mutations, which is often a predictor of poor prognosis. MET-driven resistance has been reported in up to 22% of NSCLC patients with acquired resistance to EGFR [tyrosinase kinase inhibitors (TKIs)].”
“Those patients currently have very limited targeted treatment options, and actively seek the right treatment for their disease,” he explained further.
Shun and colleagues conducted a multicenter, multi-cohort, single-arm phase 2 study evaluating the efficacy, safety and pharmacokinetics of savolitinib among MET-treatment naive patients with unresectable or metastatic METex14+ NSCLC. Objective response rate (ORR) as determined by an independent review committee was the primary endpoint, according to the abstract.
Among the 61 evaluable patients, the ORR was 47.5% (95% CI; 34.6%-60.7%) and the disease control rate was 93.4% (95% CI; 84.1%-98.2%). However, the median duration of response has not yet been reached.
Shun and colleagues reported a 6.8 month (95% CI, 4.2-13.8) median progression-free survival among all 70 patients who were treated. According to the abstract, 14.3% of patients discontinued treatment due to treatment-related adverse events. Of these, liver injury and hypersensitivity were most common, with each representing 2.9% of those who discontinued. Peripheral edema, nausea, increased AST/ALT, vomiting and hypoalbuminemia were among the most common treatment-related adverse events, with a 41.7% incidence rate of grade 3 or higher treatment-related adverse events.
“Our findings show that savolitinib may benefit patients with NSCLC with MET exon 14 skipping mutations who have failed prior systemic therapy or are unable to receive chemotherapy,” Shun said. “In lung cancer specifically, future research could also explore the potential benefit of savolitinib in combination with osimertinib in earlier lines of therapy, such as if patients with EGFR-mutated NSLSC whose tumors are resectable are treated with osimertinib, acquire resistance due to MET amplification and their cancer returns.”
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Shun L, et al. Abstract 9519. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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