Yale School of Medicine researchers have discovered that the immune-therapy drug pembrolizumab prolongs overall survival in patients with advanced non-small-cell lung cancer. The study, titled “Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial,” was published in the journal The Lancet and recently presented at the 2015 annual conference of the European Society for Medical Oncology in Singapore.
The team designed a randomized, open-label clinical trial recruiting patients previously treated for non-small-cell lung cancer who had disease progression and PD-L1 (short for programmed death-ligand 1, a protein that plays a key role in suppressing the immune response against tumors) expressed in at least 1% of their tumor cells. A total of 1,034 patients participated in the study and were randomly assigned to receive pembrolizumab 2 mg/kg (345 patients), pembrolizumab 10 mg/kg (346 patients), or docetaxel 75 mg/m2 (343 patients) every three weeks. The trial endpoints were overall survival, progression-free survival, and safety.
Researchers found that even patients expressing low levels of PD-L1 exhibited significant benefits from pembrolizumab treatment: overall survival was significantly longer for pembrolizumab 2 mg/kg and pembrolizumab 10 mg/kg when compared to docetaxel treatment. Patients with at least 50% of tumor cells expressing PD-L1 showed longer overall survival rates, with 14.9 months versus 8.2 months for pembrolizumab 2 mg/kg and docetaxel, respectively; patients treated with pembrolizumab 10 mg/kg had an overall survival of 17.3 months.
Furthermore, progression-free survival (PFS) was also significantly increased in patients treated with pembrolizumab: pembrolizumab 2 mg/kg and pembrolizumab 10 mg/kg patients had a median PFS of 5.0 and 5.2 months, respectively, when compared to 4.1 months of those in docetaxel treatment.
Roy S. Herbst, MD, the Ensign Professor of Medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale-New Haven, and the study’s corresponding author, said in a press release, “I believe we should treat patients with the best available drugs as soon as possible. Now that we have learned which patients are most likely to benefit from the anti–PD-L1 strategy, we could begin moving this drug to the earlier setting stages. In this direction, I am eager to see the results of ongoing studies testing pembrolizumab in the first-line setting and as an adjuvant after surgery to hopefully reduce high rates of lung cancer recurrence.”
These results reveal that patients with advanced non-small-cell lung cancer whose tumors express PD-L1 could benefit substantially if treated earlier with pembrolizumab therapy.