Updated overall survival (OS) findings, a secondary endpoint, from the phase 3 KEYNOTE-024 trial evaluating pembrolizumab as a first-line monotherapy in patients with non-small cell lung cancer (NSCLC) whose tumours express high levels of PD-L1 (tumour proportion score [TPS] of 50 percent or more) were announced today.

The study included patients with squamous and nonsquamous NSCLC with no EGFR or ALK genomic tumour aberrations.

Findings – which are based on more than two years of follow-up – were presented in an oral presentation at the 18th World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Yokohama, Japan.

With an additional six months of available data, results continue to show a reduction in the risk of death by 37 percent for pembrolizumab compared to chemotherapy based on more than two years of median follow-up (HR, 0.63 [95% CI, 0.47–0.86]; nominal p=0.002).

Additionally, pembrolizumab increased OS by more than one year, more than double the OS for chemotherapy (30.0 months [95% CI, 18.3–not reached]; 14.2 months [95% CI, 9.8–19.0], respectively).

“As we continue to see updated findings from this study of patients with non-small cell lung cancer in the first-line setting, practitioners are gaining valuable insights into the longer-term clinical benefit of pembrolizumab,” said Prof. Martin Reck, head of the department of thoracic oncology, LungenClinic Grosshansdorf, Germany. “The significant overall survival findings observed in KEYNOTE-024, which includes patients who have a poor prognosis, reinforce the use of pembrolizumab in appropriate patients in the first-line treatment of this disease.”

Merck has an extensive research program in NSCLC and is currently advancing multiple registration-enabling studies with pembrolizumab as monotherapy and in combination with other treatments.

“The focus of our clinical program has always been to improve survival for people with cancer,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “With these findings from KEYNOTE-024, we continue to demonstrate the potential for pembrolizumab to have a positive impact on survival outcomes in non-small cell lung cancer.”

KEYNOTE-024 studied 305 patients with metastatic NSCLC who were assigned either pembrolizumab as monotherapy (n=154) or standard of care platinum-based chemotherapy (n=151).

Enrollment criteria included: having no prior systemic chemotherapy treatment for their advanced disease, tumours without an EGFR sensitizing mutation or ALK translocation, and tumours expressing high levels of PD-L1 (TPS of 50 percent or more) as determined by a central laboratory FDA-approved test.

The primary endpoint was progression-free survival (PFS) and the key secondary endpoint was OS.

Other secondary endpoints include overall response rate (ORR) and safety. Exploratory endpoints include duration of response.

Data presented at WCLC are based on a median follow-up of 25.2 months in 305 patients and include findings from 82 patients who crossed over from the chemotherapy group to receive pembrolizumab, per study protocol, and 12 patients who received anti-PD-1 therapy outside of study crossover, totaling a 62.3 percent effective crossover rate.

With an additional six months of follow-up, an analysis of OS demonstrated that the median OS for the pembrolizumab group was 30.0 months (95% CI, 18.3–not reached) and the median OS for the chemotherapy group was 14.2 months (95% CI, 9.8–19.0).

Consistent with previously reported findings, pembrolizumab was also associated with a 37 percent reduction in the risk of death compared to chemotherapy (HR, 0.63 [95% CI, 0.47-0.86]; nominal p=0.002).

The 24-month OS rate was 51.5 percent in the pembrolizumab group compared to 34.5 percent in the chemotherapy group; at 12 months, the OS rate was 70.3 percent in the pembrolizumab (pembrolizumab) group compared to 54.8 percent in the chemotherapy group.

ORR was 45.5 percent (95% CI, 37.4-53.7) in the pembrolizumab group compared to 29.8 percent (95% CI, 22.6-37.8) in the chemotherapy group.

Median duration of response was not reached in the pembrolizumab group (range: 1.8 to 20.6 months) compared to 7.1 months (range: 2.1 to 18.1 ) in the chemotherapy group.

The safety of pembrolizumab was consistent with what has been seen in previous trials among patients with metastatic NSCLC.

In the pembrolizumab group, 31.2 percent of patients experienced Grade 3-5 treatment-related adverse events (TRAEs).

The most common TRAEs for pembrolizumab were diarrhoea, fatigue, pyrexia, pruritus, nausea, decreased appetite and rash.

The most common immune-mediated adverse events in patients receiving pembrolizumab were hypothyroidism, pneumonitis, hyperthyroidism, severe skin toxicity and infusion reactions.

There was one treatment-related death in the pembrolizumab group.

Source: BusinessWire