Advertisement


Tony S.K. Mok, MD, on NSCLC: Adagrasib vs Docetaxel in KRAS G12C–Mutated Disease

2024 ASCO Annual Meeting

Advertisement

Tony S.K. Mok, MD, of The Chinese University of Hong Kong, discusses phase III findings from the KRYSTAL-12 study, which showed that adagrasib improved progression-free survival and overall response rate over docetaxel in patients with locally advanced or metastatic non–small cell lung cancer harboring a KRAS G12C mutation who had previously received a platinum-based chemotherapy with anti–PD-(L)1 treatment.



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Crystal-XII is a randomized phase three study that compare adagrasib with docetaxel in previously treated non-small cell lung cancer, that harbored KRAS-G2LC mutation. Now this study is important. Now, as you probably know, KRAS-G2LC accounted for about 14% of all lung adenocarcinoma. And then the adagrasib, which is a covalent bonded inhibitor of the KRAS-G2LC, as demonstrated in the early phase two data, that there is actually promising response rate, progression-free survival and over-survival. And also NCCN had approved that this is a category 2A agent for patient with this mutation, and brain metastasis. However, we still need to prove it with the randomized study, and is the time that we can share with you the result. So a bit of the design. This is designed to enroll the patient with the KRAS-G2LC stage four. The patient can receive chemotherapy, and also immunotherapy either concurrently or sequentially. It's a randomized in a two-to-one fashion, total above 453 patient. Now with that, there is actually, the patient actually was able to dispose, and majority of the patient received the targeted drug, meaning at aggressive of 99% of patient, and the dosage absolute arm is about 92% patient. And overall, the progression pre-survival is much improved, with the actually median of 5.5 versus, 3.8 months, hazard ratio 0.58. And also there is a difference in the response rate. 32% versus 9%, and this is also translated into a duration of response of about 8.4 months versus about 5.3 months. There's another feature that's important, which is the intracranial response. So for a patient with the known brain metastasis, we have a intracranial response rate of 24% versus about 11%. Safety wise, actually the most common toxicity is diarrhea. And then with this, actually the patient is mostly grade one and two. And also there's some nausea and vomiting, which is actually well controlled. One toxicity that's not so clear is that there's a slight elevation of the blood creatinine. However, most of this, patient will be reversible upon c-section of the drug. So as a conclusion, I think the Crystal-12 study had confirmed the role of the adagrasib as a second line therapy for patient with the lung cancer, with the KRAS-G2LC, after failing the chemotherapy and immunotherapy. In the future, there is also the Crystal-7 study, which actually put adagrasib in the first line. It will be in combination with pembrolizumab, comparing to pembrolizumab alone in patient with actually a PTPS score of over 50%.

Related Videos

Skin Cancer

Axel Hauschild, MD, on Melanoma: Findings From the PIVOTAL Trial of Daromun vs Surgery

Axel Hauschild, MD, of Germany’s University of Kiel and University Hospital Schleswig-Holstein, discusses phase III study results on neoadjuvant intralesional daromun vs immediate surgery for patients with fully resectable, locally advanced melanoma (Abstract LBA9501).

Prostate Cancer
Genomics/Genetics

Alicia Morgans, MD, MPH, and Susan Halabi, PhD, on Prostate Cancer: New Findings on Classifying Patients Into Risk Groups

Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Susan Halabi, PhD, of the Duke Cancer Institute and Duke University School of Medicine, discuss a clinical-genetic model that identified novel circulating tumor DNA alterations that are prognostic of overall survival and may help to classify patients with metastatic castration-resistant prostate cancer into risk groups useful for selecting trial participants (Abstract 5007).

Leukemia

Yucai Wang, MD, PhD, on Richter Transformation of CLL: Findings on Combination Therapy With an Immune Checkpoint Inhibitor

Yucai Wang, MD, PhD, of the Mayo Clinic, discusses the increased efficacy of combination therapy with pembrolizumab plus a BCR kinase inhibitor compared with pembrolizumab alone in patients with Richter transformation of chronic lymphocytic leukemia (CLL; Abstract 7050).

Kidney Cancer

Brian I. Rini, MD, on Renal Cell Carcinoma: Exploratory Biomarker Results

Brian I. Rini, MD, of Vanderbilt Ingram Cancer Center, discusses phase III findings of the KEYNOTE-426 study of pembrolizumab plus axitinib vs sunitinib for patients with advanced renal cell carcinoma. He details the exploratory biomarker results, including RNA sequencing, whole-exome sequencing, and PD-L1 (Abstract 4505).

Prostate Cancer

Alicia Morgans, MD, MPH, and Karim Fizazi, MD, PhD, on Prostate Cancer: Study Findings on Health-Related Quality of Life and Pain

Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, PhD, of Institut Gustave Roussy and the University of Paris-Saclay, discuss a second interim analysis of the health-related quality of life and pain outcomes in the PSMAfore study (Abstract 5003).

Advertisement

Advertisement




Advertisement