James Chih-Hsin Yang, MD, PhD, on Metastatic Nonsquamous NSCLC: Evaluating Pemetrexed and Platinum With or Without Pembrolizumab

2023 ASCO Annual Meeting


James Chih-Hsin Yang, MD, PhD, of the National Taiwan University Hospital and National Taiwan University Cancer Center, discusses the latest data from the phase III KEYNOTE-789 study, which evaluated the efficacy and safety of pemetrexed plus platinum chemotherapy (carboplatin or cisplatin) with or without pembrolizumab in the treatment of adults with EGFR tyrosine kinase inhibitor–resistant, EGFR–mutated, metastatic nonsquamous non–small cell lung cancer (NSCLC) (Abstract LBA9000).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
James Chih-Hsin Yang: Patients who had EGFR mutation, stage four non-small cell lung cancer, the standard of care is tyrosine kinase inhibitors as a first line. When they fail, they have to receive chemotherapy as a standard of care. KEYNOTE-789 is a randomized phase three study, testing whether adding pembrolizumab to the standard chemotherapy is going to help overall survival and progression-free survival. 492 patients who are randomized into two arms. One, pembrolizumab plus end of care chemotherapy versus chemotherapy plus placebo. The co-primary endpoints were progression-free survival and overall survival. There were three interim analysis. Progression-free survival time were done at the interim analysis two. The hazard ratio was 0.8, which nearly touched the statistical significant P value of boundary 0.0117 and therefore miss the endpoint. The overall survival endpoint was done at the interim analysis three, which was then final analysis 42 months after the last patient's randomized. The overall survival hazard ratio was 0.84, was also statistically not significant. We also look at the pathological and clinical factors. We try to figure out whether patients with different characteristics can benefit from pembrolizumab adding to chemotherapy. Unfortunately, there was only one factor that seems to help these patients, which is PD-L1 status. Patients who had PD-L1 more than 1%, which is close to 50% of the population, the hazard ratio for overall survival was 0.77. Where those patients who did not have PD-L1 expression, their hazard ratio for overall survival was 0.91. So, we had a study that we cannot change the standard practice, yet the finding that PD-L1 status may help us to choose a patient when asked for future study.

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