Pembrolizumab demonstrated activity in PD-L1–expressing NSCLC

CHICAGO — Pembrolizumab was safe and effective in patients with locally advanced or metastatic non–small cell lung cancer that strongly expressed PD-L1, according to study results presented at the ASCO Annual Meeting.

Edward B. Garon, MD, assistant clinical professor and director of the thoracic oncology program at the David Geffen School of Medicine at the University of California, Los Angeles, and colleagues sought to evaluate pembrolizumab (Merck) — previously known as lambrolizumab and MK-3475 — among patients with previously treated advanced NSCLC.

Edward B. Garon

“We presented the initial data from lung cancer patients at the World Conference on Lung Cancer in Sydney last fall,” Garon told HemOnc Today. “The question at that time was whether the impressive efficacy and tolerable safety profile could be confirmed in a larger population. We have now demonstrated similar results in over 200 additional patients.”

The analysis included 217 patients who were tested for PD-L1 expression using immunohistochemistry (IHC).

Garon and colleagues assigned 58 PD-L1 positive patients to 10 mg/kg pembrolizumab every 2 weeks, and 119 patients received 10 mg/kg every 3 weeks. Forty PD-L1 negative patients were assigned the 10 mg/kg dose every 2 weeks.

The objective response rate according to RECIST criteria among all patients was 20% (95% CI, 15-26). The response rate observed among current or former smokers was 26% (95% CI, 19-35), whereas only 8% (95% CI, 3-18) of never smokers responded.

Researchers reported a higher response rate among patients who were PD-L1 positive (23% vs. 9%).

The median time to response was 9 weeks (range, 6-31) in the PD-L1–positive cohort and 14 weeks (range, 9-18) in the PD-L1–negative cohort.

PD-L1–positive patients achieved a median PFS of 11 weeks (95% CI, 9-16), and PD-L1 negative patients achieved a 10-week median PFS (95% CI, 9-16).

Among PD-L1 positive patients, 26% (95% CI, 15-40) of those who received pembrolizumab every 2 weeks demonstrated a response, compared with 21% (95% CI, 13-30) who received treatment every 3 weeks. The median time to response was 10 weeks (range, 6-26) in the 2-week cohort and 9 weeks (range, 7-31) in the 3-week cohort.

Most responders who expressed PD-L1 were still receiving treatment at the time of the data cutoff (82%).

“The results in the PD-L1–positive group are sufficiently good to consider clinical trials in a variety of settings with a more favorable anticipated prognosis,” Garon said. “The role of pembrolizumab in PD-L1–low or –negative patients will require further evaluation, as it is unclear how to contextualize our results in the difficult clinical scenario of previously treated NSCLC.”

Sixty-four percent of patients experienced at least one treatment-related adverse event, and 10% experienced one or more grade ≥3 adverse events.

The most common adverse events of any grade were fatigue (20%), arthralgia (9%), decreased appetite (9%) and pruritus (8%).

A phase 2/phase 3 trial designed to evaluate two doses of pembrolizumab with docetaxel in NSCLC, as well as a phase 1/phase 2 trial designed to evaluate the agent with ipilimumab (Yervoy, Bristol-Myers Squibb) or chemotherapy, are both ongoing.

“Although responses were more common in patients with PD-L1–positive tumors, particularly a subset with greater than 50% of cells positive by IHC using a clinical trial assay, that observation will need to be validated,” Garon said.

For more information:

Garon EB. Abstract #8020. Presented at: ASCO Annual Meeting; May 30-June 3, 2014; Chicago.

Disclosure: The researchers report consultant/advisory roles with, leadership/employment positions with and research funding from Bayer, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, ImmunoGen, MedImmune, Merck, Novartis and Xcovery.