COPENHAGEN, Denmark — Pembrolizumab significantly extended PFS and OS compared with platinum-based chemotherapy among untreated patients with advanced non–small cell lung cancer whose tumors had high PD-L1 expression, according to results of the KEYNOTE-024 trial presented at the European Society for Medical Oncology Congress.
Pembrolizumab (Keytruda, Merck) also appeared better tolerated.
“For this group of patients ... this option appears quite favorable,” Martin Reck, MD, PhD, head of the department of thoracic oncology and head of the clinical trial department in the department of thoracic oncology at Lung Clinic Grosshansdorf in Germany, said during a press conference. “This data will completely change the management of patients with advanced NSCLC.”
Platinum-based chemotherapy is the standard of care for patients with advanced NSCLC who have no targeted oncogenic alterations.
However, pembrolizumab — a humanized monoclonal immunoglobulin G4 antibody directed against programmed death receptor 1 (PD-1) — has demonstrated particularly strong efficacy in patients whose tumors express programed death ligand 1 (PD-L1).
The randomized, open-label, phase 3 KEYNOTE-024 trial included 305 patients with treatment-naive advanced NSCLC who had PD-L1 expression on at least 50% of their tumor cells. Eligible patients had no translocation of the anaplastic lymphoma kinase gene, no sensitizing mutation of epidermal growth factor receptor, no untreated brain metastases and no active autoimmune disease.
Researchers randomly assigned patients to 200 mg pembrolizumab every 3 weeks or investigator’s choice of platinum-based chemotherapy. Treatment continued until disease progression. Patients assigned chemotherapy who progressed during treatment were allowed to cross over to pembrolizumab.
PFS — assessed by blinded, independent, central radiologic review — served as the primary endpoint. OS, objective response rate and safety served as secondary endpoints.
Pembrolizumab conferred significant improvements in median PFS (10.3 months vs. 6 months; HR = 0.5; 95% CI, 0.37-0.68), 6-month PFS (62.1% vs. 50.3%), median OS (HR = 0.6; 95% CI, 0.41-0.89), 6-month OS (80% vs. 72%; HR = 0.6) and 12-month OS (70% vs. 54%).
“This improvement in OS has been observed despite a crossover rate of approximately 50% to anti–PD-1 agents,” Reck said.
Researchers also reported a higher response rate (44.8% vs. 27.8%) and a longer median duration of response (not reached vs. 6.3 months) among pembrolizumab-treated patients.
“Comorbidity also was in favor of pembrolizumab, with a lower number of treatment-related adverse events,” Reck said.
Fewer patients assigned pembrolizumab experienced any-grade treatment-related adverse events (73.4% vs. 90%), as well as grade 3 to grade 5 treatment-related adverse events (26.6% vs. 53.3%).
Treatment-related adverse effects observed in pembrolizumab-treated patients appeared consistent with those reported in prior trials of the drug.
“This is a landmark trial for the 30% of patients with advanced NSCLC who are high expressers of PD-L1,” Reck said in a press release. “The new treatment algorithm should include upfront testing for PD-L1 expression to identify patients who will benefit from first-line treatment with pembrolizumab.”
However, he described the treatment option as “primarily an opportunity for patients without oncogenic alterations,” and he emphasized more data are needed to determine the potential benefit in patients who do have oncogenic alterations. – by Mark Leiser
For more information: Reck M, et al. LBA8_PR. Presented at: European Society for Medical Oncology Congress; Oct. 7-11, 2016; Copenhagen, Denmark.
Disclosure: Merck provided funding for this study. Reck reports personal fees outside the submitted work from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Hoffmann-La Roche, Merck Sharpe & Dohme, Novartis and Pfizer. Please see the abstract for a list of all other researchers’ relevant financial disclosures.