Merck reports data from KEYNOTE-024, KEYNOTE-021
Merck announced results from two studies of KEYTRUDA in the first-line treatment of patients with metastatic non-small cell lung cancer at the ESMO 2016 Congress. In KEYNOTE-024, which evaluated squamous and non-squamous NSCLC patients whose tumors expressed high levels of PD-L1, KEYTRUDA provided a 50 percent reduction in the risk of disease progression or death and a 40 percent reduction in the risk of death compared to platinum doublet, the current standard of care. The median follow-up was 11.2 months. The median PFS for KEYTRUDA was 10.3 months compared to 6.0 months for chemotherapy. At six months, 62.1 percent of patients treated with KEYTRUDA were alive and had no disease progression compared to 50.3 percent of those receiving chemotherapy. This benefit was observed in all study subgroups. ORR was 44.8 percent for patients receiving KEYTRUDA, including six complete responses, compared to 27.8 percent with chemotherapy, including one complete response. The median duration of response was not reached with KEYTRUDA, with a range of 1.9+ to 14.5+ months. The median duration of response with the chemotherapy group was 6.3 months. Median time to response was 2.2 months for both groups. The safety of KEYTRUDA was consistent with what has been seen in previous trials among patients with metastatic NSCLC. There was one treatment-related death in a patient receiving KEYTRUDA -- cause unknown. In KEYNOTE-021, Cohort G, which included patients with metastatic non-squamous NSCLC regardless of PD-L1 expression level, KEYTRUDA plus chemotherapy -- carboplatin plus pemetrexed -- achieved a 55 percent objective response rate compared to 29 percent for chemotherapy alone, the standard of care, and reduced the risk of disease progression or death by 47 percent. All responses were partial. Median duration of response was not reached in either group, with a range of 1.4+-13.0+ for KEYTRUDA plus chemotherapy and 1.4+-15.2+ for chemotherapy alone. Responses in both groups were durable, with 88 percent of responders in the KEYTRUDA plus chemotherapy group and 78 percent of responders in the chemotherapy alone group experiencing ongoing response at the time of data cut-off. Additionally, the KEYTRUDA combination significantly reduced the risk of disease progression or death compared to chemotherapy alone. Median PFS was 13.0 months with KEYTRUDA plus chemotherapy compared to 8.9 months with chemotherapy alone. OS was similar between the two arms, with 92 percent survival at six months in both, and 75 percent and 72 percent survival at 12 months in the KEYTRUDA combination and chemotherapy alone, respectively. Of treated patients on the KEYTRUDA plus chemotherapy arm, 47 percent remained on treatment as of the cut-off date, compared to 31 percent on chemotherapy alone. Of the treated patients who discontinued treatment on the chemotherapy-only arm, 52 percent subsequently received anti-PD-L1 therapy, with 32 percent crossing over to KEYTRUDA monotherapy as allowed by the study protocol and 19 percent receiving it outside of study crossover. The most common immune-mediated adverse events in patients receiving KEYTRUDA plus chemotherapy were hypothyroidism and hyperthyroidism. Additionally, pneumonitis, infusion reactions, and severe skin toxicity were noted. These immune-mediated adverse events occurred at similar rates to patients receiving KEYTRUDA as a single agent. There was one treatment-related death from sepsis in a patient receiving KEYTRUDA plus chemotherapy, and two -- one from sepsis and one from pancytopenia -- in patients receiving chemotherapy alone.