Anne S. Tsao, MD reviewing Herbst RS et al. Lancet 2015 Dec 19.

Survival was significantly improved with pembrolizumab versus docetaxel in patients with pretreated PD-L1–positive advanced NSCLC.

Following publication of the phase Ib KEYNOTE-001 study (NEJM JW Oncol Hematol Jun 2015, and N Engl J Med 2015; 372:2018), pembrolizumab (MK-3475), an IgG4 monoclonal antibody to PD-1, was granted accelerated FDA approval for evaluation in chemorefractory non–small-cell lung cancer (NSCLC) that expresses PD-L1.

Now, investigators have conducted an industry-funded, international phase II/III, randomized, controlled, open-label trial (KEYNOTE-010), in which previously treated NSCLC patients who expressed PD-L1 in at least 1% of tumor cells received one of three treatments: pembrolizumab (2 mg/kg), pembrolizumab (10 mg/kg), or docetaxel (75 mg/m2).

Results were as follows:

For the entire study population, median overall survival (OS) was improved with both low-dose and high-dose pembrolizumab versus docetaxel (10.4 and 12.7 months vs. 8.5 months, respectively); progression-free survival (PFS) was not improved with pembrolizumab for these patients.

For patients with ≥50% of tumor cells expressing PD-L1, median OS was significantly improved with low-dose pembrolizumab versus docetaxel (14.9 vs. 8.2 months; P=0.0002) and with high-dose pembrolizumab versus docetaxel (17.3 vs. 8.2 months; P<0.0001). Median PFS was also significantly improved for these patients, with both low-dose and high-dose pembrolizumab versus docetaxel (5.0 and 5.2 months vs. 4.1 months; P=0.0001 for both).

Both low-dose and high-dose pembrolizumab were associated with fewer grade 3–5 treatment-related adverse events than docetaxel (13% and 16% vs. 35%, respectively).

Citation(s):

Herbst RS et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial. Lancet 2015 Dec 19; [e-pub].

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