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
Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses results of a phase III study showing that progression-free survival with ibrutinib plus obinutuzumab plus venetoclax is not superior to ibrutinib plus obinutuzumab for treatment-naive older patients with chronic lymphocytic leukemia (CLL) in the setting of the COVID-19 pandemic. Long-term follow-up will determine whether there are advantages to obinutuzumab plus venetoclax, with special attention to measurable residual disease and therapy discontinuation (Abstract 7500).
The ASCO Post Staff
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
The ASCO Post Staff
Smitha Krishnamurthi, MD, of the Cleveland Clinic, and Deb Schrag, MD, MPH, of Memorial Sloan Kettering Cancer Center, discuss phase III findings from the PROSPECT trial, which showed FOLFOX chemotherapy with selective use of radiation therapy and sensitizing fluoropyrimidine (5FUCRT) is noninferior to 5FUCRT for the neoadjuvant treatment of patients with locally advanced rectal cancer, prior to low anterior resection with total mesorectal excision (Abstract LBA2).
The ASCO Post Staff
Lisa M. DeAngelis, MD, and Ingo K. Mellinghoff, MD, both of Memorial Sloan Kettering Cancer Center, discuss findings from the INDIGO trial showing that the IDH1/2 inhibitor vorasidenib improves progression-free survival for patients with residual or recurrent grade 2 glioma with an IDH1/2 mutation. These data demonstrate the clinical benefit of vorasidenib in this patient population for whom chemotherapy and radiotherapy are being delayed.
The ASCO Post Staff
Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill, and Dennis J. Slamon, MD, PhD, of the University of California, Los Angeles, discuss phase III study findings on ribociclib plus endocrine therapy as adjuvant treatment in patients with hormone receptor–positive, HER2-negative early breast cancer. When added to standard-of-care endocrine therapy, ribociclib improved invasive disease–free survival with a well-tolerated safety profile (Abstract LBA500).
