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).
Transcript
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.
The ASCO Post Staff
Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Zeynep Eroglu, MD, of H. Lee Moffitt Cancer Center and Research Institute, discusses phase II findings showing that in patients with BRAF-mutant metastatic melanoma, dabrafenib plus trametinib and navitoclax (DTN) was associated with a complete response rate of 20% and an overall response rate of 84%. Additionally, there was a trend toward improved overall survival in patients treated with DTN compared with dabrafenib plus trametinib alone; the difference in overall survival was more pronounced in patients with a smaller tumor burden (Abstract 9511).
The ASCO Post Staff
Nirav N. Shah, MD, of the Medical College of Wisconsin, discusses the efficacy and safety of pirtobrutinib, a highly selective, noncovalent BTK inhibitor, studied for more than 3 years in the BRUIN trial. The results showed that the use of pirtobrutinib continues to have durable efficacy and a favorable safety profile in heavily pretreated patients with relapsed or refractory mantle cell lymphoma and prior BTK inhibitor therapy. Responses were observed in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki67 index, and TP53 mutations (Abstract 7514).
The ASCO Post Staff
Narjust Florez, MD, of Dana-Farber Cancer Institute, and Ticiana Leal, MD, of Winship Cancer Institute of Emory University, discuss the use of tumor treating fields therapy, in which electric fields disrupt processes critical for cancer cell viability. Already approved by the FDA to treat glioblastoma and mesothelioma, the treatment has extended overall survival in this phase III study of patients with metastatic non–small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy, without exacerbating systemic toxicities (Abstract LBA9005).
The ASCO Post Staff
Guillermo Garcia-Manero, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings from the COMMANDS trial. Compared with epoetin alfa, luspatercept improved red blood cell transfusion independence and erythroid response, as well as the duration of response in erythropoiesis-stimulating agent–naive, transfusion-dependent patients with lower‐risk myelodysplastic syndromes (Abstract 7003).
The ASCO Post Staff
Rana R. McKay, MD, of the University of California, San Diego, and Brian I. Rini, MD, of Vanderbilt-Ingram Cancer Center, discuss the 5-year follow-up results with the combination of a checkpoint inhibitor plus a VEGFR tyrosine kinase inhibitor as first-line treatment for patients with advanced clear cell renal cell carcinoma (RCC). Pembrolizumab plus axitinib continued to demonstrate improved survival outcomes as well as overall response rate vs sunitinib for patients with previously untreated disease (Abstract LBA4501).
