Osimertinib plus selumetinib shows promise in advanced NSCLC

The combination of osimertinib plus selumetinib exhibits antitumour activity in patients with MET-negative, EGFRm advanced nonsmall cell lung cancer (NSCLC), with the safety profile consistent with the reported safety data for the drugs, according to data from the small open-label, phase Ib study.

The study included 47 patients (aged ≥18 years) with MET-negative, EGFR-mutated advanced NSCLC who had progressed on EGFR-tyrosine kinase inhibitors (TKIs). Patients were grouped based on prior first- or second-generation EGFR-TKI (n=12) or T790M-directed EGFR-TKI (n=35). They were given osimertinib 80 mg every day and intermittent selumetinib 75 mg twice a day orally.

Researchers assessed safety and tolerability as the primary endpoint. They also looked at the combination’s antitumor activity, as defined by objective response rate (ORR), and progression-free survival (PFS).

Of the patients, 94 percent were Asian and 30 (64 percent) had baseline exon 19 deletion. With regard to the primary endpoint, the most common adverse events (AEs) were diarrhoea (89 percent), reduced appetite (40 percent), and stomatitis (32 percent.). A total of 11 patients (23 percent) experienced grade ≥3 AE that was possibly related to selumetinib treatment.

ORR was 34.0 percent (95 percent confidence interval [CI], 20.9–49.3) overall, 66.7 percent (95 percent CI, 34.9–90.1) in the prior first- or second-generation EGFR-TKI group, and 22.9 percent (95 percent CI, 10.4–40.1) in the prior T790M-directed EGFR-TKI group. The corresponding median PFS was 4.2 months (95 percent CI, 2.7–7.2), 15.0 (95 percent CI, 2.7–33.0), and 2.8 (95 percent CI, 1.6–5.5), respectively.