Keytruda (pembrolizumab) showed improvements in overall survival, progression-free survival and objective response rate as monotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥1%), regardless of KRAS mutational status.
These findings, which are based on an exploratory analysis of the pivotal phase III KEYNOTE-042 trial, were presented in a proffered paper presentation (Abstract #LBA4) at the European Society for Medical Oncology Immuno-Oncology Congress 2019 in Geneva.
“KRAS mutations occur in approximately 20% of people with non-small cell lung cancer, and some previous studies have suggested that these mutations are associated with a poorer response to treatment,” said Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “It was therefore encouraging to see in this exploratory analysis that Keytruda monotherapy was associated with a survival benefit in certain patients with metastatic nonsquamous non-small cell lung cancer, regardless of KRAS mutational status.”
The objective of the exploratory analysis was to assess the prevalence of KRAS mutations and their association with efficacy in the KEYNOTE-042 trial. Of the 1,274 untreated patients with metastatic nonsquamous NSCLC whose tumors expressed PD-L1 (TPS ≥1%) enrolled in KEYNOTE-042, 301 patients had KRAS evaluable data (n=232 without any KRAS mutation; n=69 with any KRAS mutation, including n=29 with the KRAS G12C mutation).
Tissue tumor mutational burden (tTMB) and KRAS mutational status were determined by whole-exome sequencing (WES) of tumor tissue and matched normal DNA (blood). Patients were randomized 1:1 to receive Keytruda 200 mg intravenously every three weeks (n=637) or investigator’s choice of chemotherapy (pemetrexed or paclitaxel) (n=637). Treatment continued until progression of disease or unacceptable toxicity. The primary endpoint was OS with a TPS of ≥50%, ≥20% and ≥1%, which were assessed sequentially. The secondary endpoints were PFS and ORR.
Findings from this exploratory analysis showed that Keytruda monotherapy was associated with improved clinical outcomes, regardless of KRAS mutational status, in patients with metastatic nonsquamous NSCLC versus chemotherapy. In this analysis, Keytruda reduced the risk of death by 58% (HR=0.42 [95% CI, 0.22-0.81]) in patients with any KRAS mutation and by 72% (HR=0.28 [95% CI, 0.09-0.86]) in patients with the KRAS G12C mutation compared to chemotherapy.
