Pooled Analysis Shows Merck’s KEYTRUDA® Plus Chemotherapy Reduces Death Risk by 44% in First-Line Treatment of PD-L1-Negative Advanced NSCLC
Sep 18, 2019 11:08
CST Updated
11:08
MSD
Pharmaceutical R&D and Manufacturer
September 18, 2019 /BioValleyBIOON/ -- Merck & Co. recently announced the latest pooled subgroup analysis data for Keytruda (Keytruda, generic name: pembrolizumab) as a first-line treatment. The results showed that in tumors not expressing PD-L1 (TumorIn patients with advanced non-squamous and squamous non-small cell lung cancer (NSCLC) with a Tumor Proportion Score (TPS) < 1%, Keytruda combined with chemotherapy improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
These results are derived from a pooled subgroup analysis of 428 patients across three studies: KEYNOTE-189, KEYNOTE-407, and KEYNOTE-021 (Cohort G). The analysis demonstrated that Keytruda plus chemotherapy reduced the risk of death by 44% compared with chemotherapy alone (HR=0.56 [95% CI: 0.43–0.73]). The 12-month overall survival rates were 66% in the Keytruda plus chemotherapy group versus 47% in the chemotherapy group, and the 18-month overall survival rates were 52% versus 29%, respectively. The median overall survival (OS) was 19.0 months (95% CI: 15.2–24.0) in the Keytruda plus chemotherapy group and 11.0 months (95% CI: 9.2–13.5) in the chemotherapy group.
Furthermore, compared with chemotherapy, Keytruda plus chemotherapy reduced the risk of disease progression or death by 33% (HR=0.67 [95% CI: 0.54–0.84]). The 12-month and 18-month progression-free survival (PFS) rates were 29% and 22%, respectively, in the Keytruda plus chemotherapy group, versus 17% and 9%, respectively, in the chemotherapy group. The median PFS was 6.5 months (95% CI: 6.2–8.5) in the Keytruda plus chemotherapy group and 5.4 months (95% CI: 4.7–6.2) in the chemotherapy group.
In terms of overall response rate (ORR), the Keytruda plus chemotherapy group was 46.9%, and the chemotherapy group was 28.6%. The median duration of response (DOR) in the Keytruda plus chemotherapy group was 7.9 months (range: 1.1+ to 28.4+), and in the chemotherapy group, it was 6.7 months (range: 1.4+ to 30.1+). The proportion of patients with DOR ≥12 months was 42.4% in the Keytruda plus chemotherapy group and 35.3% in the chemotherapy group.
In this analysis, the safety profile of Keytruda was consistent with previously reported findings in patients with advanced NSCLC. The incidence of grade 3–5 adverse events was 68% (n=165) in the Keytruda plus chemotherapy group and 72% (n=131) in the chemotherapy group. The incidence of grade 3–5 adverse events leading to death was 9% (n=23) in the Keytruda plus chemotherapy group and 6% (n=11) in the chemotherapy group. Grade 3–5 immune-mediatedAdverse ReactionsThe incidence of infusion reactions was 11% (n=27) in the Keytruda plus chemotherapy group and 3% (n=5) in the chemotherapy group. The mortality rate due to immune-mediated adverse events and infusion reactions was 1% (n=2) in the Keytruda plus chemotherapy group, with no deaths reported in the chemotherapy group.
Jonathan Cheng, Vice President of Oncology Clinical Research at MSD Research Laboratories, stated: “The goal of our robust clinical development program in lung cancer has always been to extend the survival of patients diagnosed with this fatal and aggressive disease. A pooled analysis of three randomized studies in advanced non-small cell lung cancer showed that Keytruda in combination with chemotherapy improved newDiagnosisofTumorOverall survival in patients not expressing PD-L1.”
Hossein Borghaei, Director of the Thoracic Oncology Program at Fox Chase Cancer Center in the United States, stated: “According toClinical TrialGiven the observed overall survival benefit, Keytruda in combination with chemotherapy has become an important first-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Encouragingly, in this subgroup analysis, first-line treatment with Keytruda in combination with chemotherapy willTumor"The risk of death was reduced by 44% in patients with advanced non-small cell lung cancer (NSCLC), either non-squamous or squamous epithelial type, whose cells do not express PD-L1."(Bioon.com)