Advancing Treatment for Non–Small Cell Lung Cancer: Exploring the Results of Adagrasib With Alexander Spira, MD, PhD, FACP

At the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Alexander Spira, MD, PhD, FACP, Director of the Thoracic and Phase I Program at the Virginia Cancer Specialists, the US Oncology Network, met with Oncology Data Advisor to discuss his presentation about adagrasib for KRAS G12–mutated non–small cell lung cancer with active central nervous system (CNS) metastases.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. I’m here with Dr. Alexander Spira, Director of the Thoracic and Phase I Program for the Virginia Cancer Specialists, the US Oncology Network. He just presented his research as part of the oral abstract session on non–small cell lung cancer at the ASCO 2022 Annual Meeting, and it is also being published in today’s New England Journal of Medicine.

Dr. Spira, would you like to comment on the significance of these results of adagrasib for KRASG12C–mutated non–small cell lung cancer?

Alexander Spira, MD, PhD, FACP: Thanks. So, we looked at adagrasib for KRASG12C–mutated non–small cell lung cancer in the second line and beyond. The overall response rate was 43%, which is very promising. It was a relatively well-tolerated drug. Although there were some dose reductions, only 7% of patients discontinued. It’s exciting because we presented the beginning of some brain metastases data. There’ll be a follow-up presentation on Monday, really looking at this in detail in a larger cohort of patients with untreated brain metastases. So, there’s an excitement about that because that will be the first real evidence of CNS data.

But putting the two together, this appears to be a very good option for our patients. Hopefully it’ll get approved in very short order. There is already an approved drug, sotorasib, and it’s always nice to have another one. It’s a big step forward for our patients, and again, a proven concept for these patients with KRASG12C mutation.

Oncology Data Advisor: How do you think these results compare with the results for sotorasib?

Dr. Spira: Very similar. As I said, there are subtle differences between both studies; but again, not doing cross-trial comparisons, we have confidence in those overlaps. We think they’re very similar, as I mentioned in my discussion today.

Oncology Data Advisor: As mentioned in the discussion today, also, do you think if you reduce the dose a little, you’ll have even less treatment-related toxicity?

Dr. Spira: One of the big concerns, obviously, is side effect and toxicity. I think hopefully with the reduced dose, that’ll be a little bit better tolerated. Some studies are going on right now. They’re looking at a tablet formulation. We believe that may get rid of some of the nausea and gastrointestinal (GI) side effects, as well as looking at patients at 400 mg twice a day. They saw similar things with sotorasib. There is actually an ongoing study right now comparing 240 mg versus 960 mg because of some of the same concerns.

Oncology Data Advisor: How long do you think it will take to get this into the first-line setting, maybe in combination?

Dr. Spira: A little while, right? I mean, those studies are ongoing. It’s being combined with checkpoint inhibitors. We have to finish the safety studies. We’ll hopefully have some data in short order, first regarding safety, and then the randomized study most likely going forward.

Oncology Data Advisor: Thanks. Is there anything else you’d like to add?

Dr. Spira: Not at all.

Oncology Data Advisor: Thank you so much.

About Dr. Spira

Alexander Spira, MD, PhD, FACP, is Director of the Thoracic and Phase I Program for Virginia Cancer Specialists of the US Oncology Network. He is highly involved in advancing medicine and providing the best care with targeted treatment therapies for his patients with non–small cell lung cancer. Dr. Spira has been recognized as and awarded Top Doctor in multiple publications, including Northern Virginia Magazine and Washingtonian Magazine, consistently since 2018. In his free time, he enjoys spending time with his family and coaching children’s sports teams.

For More Information

Spira AI, Riely GJ, Gadgeel SM, et al (2022). KRYSTAL-1: Activity and safety of adagrasib (MRTX849) in patients with advanced/metastatic non–small cell lung cancer (NSCLC) harboring a KRASG12C mutation. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_16). Abstract 9002. DOI:10.1200/JCO.2022.40.16_suppl.9002

Jänne PA, Riely GJ, Gadgeel SM, et al (2022). Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation. N Engl J Med, 387(2):120-131. DOI:10.1056/NEJMoa2204619

Sabari J, Spira AI, Heist RS, et al (2022). Activity of adagrasib (MRTX849) in patients with KRASG12C -mutated NSCLC and active, untreated CNS metastases in the KRYSTAL-1 trial. J Clin Oncol (ASCO Annual Meeting Abstracts), 40(suppl_17). Abstract LBA9009. DOI:10.1200/JCO.2022.40.17_suppl.LBA9009

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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