ESMO Asia 2015: Results From the KEYNOTE-010 Trial Show Pembrolizumab Benefit in Patients With NSCLC
More patients with advanced non–small cell lung cancer (NSCLC) could benefit from pembrolizumab (Keytruda), said Roy Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven. Dr. Herbst presented promising results from the pivotal phase II/III KEYNOTE-010 trial at the European Society for Medical Oncology (ESMO) Asia Congress in Singapore (Abstract LBA3), in conjunction with a publication by Herbst et al in The Lancet.
The study showed that two doses of the anti–programmed cell death ligand 1 (PD-L1) antibody pembrolizumab (the U.S. Food and Drug Administration–approved 2-mg/kg dose and an investigational 10-mg/kg dose) each given every 3 weeks, improves median survival in all PD–L1–positive patients compared with docetaxel. The benefit is even greater in the group of patients with PD-L1 staining in ≥ 50% of tumor cells.
Pembrolizumab has demonstrated clinical activity in multiple tumor types, including benefit over standard-of-care therapy in melanoma and lung cancer. By blocking the PD-1/PD-L1 pathway, which has a crucial role in neoplastic growth when activated, the drug has shown its durable antitumor activity and acceptable toxicity in treatment-naive and previously treated advanced NSCLC patients.
Study Findings
The open-label KEYNOTE-010 trial is the first study to assess the benefits of immunotherapy as second- or later-line treatment in patients with refractory lung cancer selected for PD-L1 expression. From August 2013 to April 2015, 1,034 patients with advanced NSCLC from 24 countries were randomly assigned to pembrolizumab (2 mg/kg or 10 mg/kg) or docetaxel. All patients had experienced disease progression after platinum-containing systemic therapy and were stratified by PD-L1 expression level (tumor proportion score ≥ 50% vs 1%–49%).
“The topline results show that both groups of patients receiving pembrolizumab experience a survival benefit compared to docetaxel,” Dr. Herbst said. “As expected, at the highest biomarker expression, the results were even better with a hazard ratio of 0.54 and 0.50 at the two doses of pembrolizumab, respectively. Treatment with pembrolizumab was associated with longer overall survival compared to docetaxel (median, 14.9 and 17.3 months with 2 mg/kg and 10 mg/kg of pembrolizumab and 8.2 months with docetaxel)."
He continued, “We additionally observed a quite clear benefit in patients who expressed > 1% PD-L1 positivity in the tumor, with hazard ratios for overall survival of 0.71 and 0.61 in the pembrolizumab arms (at 2 mg/kg and 10 mg/kg, respectively). These results give further support for broadening the availability of pembrolizumab for all patients with PD-L1 expression over 1%.”
In this trial, the safety profile of pembrolizumab was consistent with that from previous NSCLC studies. “Data from KEYNOTE-010 further supports the efficacy, safety, and tolerability of pembrolizumab in patients with advanced-stage NSCLC,” said Ross Soo, MD, Adjunct Principal Investigator, Cancer Science Institute of Singapore, who was not involved in the study. “The drug is not yet approved in Asia and in Europe, and this study could help in this direction.”
Looking Ahead
“The hazard ratio for overall survival favors pembrolizumab as compared with the recently approved second-line treatment options in advanced-stage NSCLC such as docetaxel plus ramucirumab [Cyramza] or docetaxel plus nintedanib [Ofev],” Dr. Soo said. “However, cross-trial comparisons should be interpreted with caution. In the absence of a direct head-to-head comparison, the choice of the specific PD-1 inhibitor relies on different factors such as costs of treatment, scheduling, and availability of biomarker testing.”
Future studies are needed to assess whether patients who express PD-L1 in less than 1% of tumor cells would have some benefits from pembrolizumab. “Data from the KEYNOTE-010 study suggests that pembrolizumab would be given to all patients with PD-L1 expression, and this could have an impact on current strategies for lung cancer,” Dr. Herbst concluded. “I believe we should use the best available weapons first. Now that we have learned which patients are most likely to benefit from the anti–PD-L1 strategy, we could start to move this weapon to the earlier stages. In this direction, I am eager to see the results of ongoing studies testing pembrolizumab in the first-line setting and eventually prevent the recurrence of lung cancer, which is still at high rates.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
