ASCO Highlights for Metastatic Non-Small Cell Lung Cancer

The American Society of Clinical Oncology annual meeting showcased new findings in the field of lung cancer that might immediately change practice, with others pointing toward exciting future opportunities.

In this exclusive MedPage Today video, James Stevenson, MD, of the Cleveland Clinic in Ohio, discusses some of the highlights in metastatic non-small cell lung cancer.

Following is a transcript of his remarks:

The major abstracts from the metastatic non-small cell lung cancer oral session involved one trial that looked at the combination of pembrolizumab [Keytruda] and ramucirumab [Cyramza] after frontline immune checkpoint inhibitor therapy and platinum-based chemotherapy. This was a positive trial in that pembrolizumab plus ramucirumab showed improved survival when compared to standard-of-care chemotherapy by over 3 months. So the endpoint was met.

This was a randomized phase II trial, not definitely practice changing yet, but sent a good signal that will make it worthy of a phase III trial. And again, we’re looking for improving on therapies in the post-checkpoint inhibitor setting in metastatic non-small cell lung cancer.

Also in that session, we heard about a drug called adagrasib, which is a KRAS G12C tyrosine kinase inhibitor. And it’s an oral agent that showed activity in patients with KRAS G12C mutations — non-small cell lung cancer patients we’re talking about here. And the response rate was over 40%. Again, showing clear activity of this drug in this selected population. So this is a drug that may get approved in the not-too-distant future for us to use in the clinic.

It’ll be the second KRAS G12C inhibitor that we have. We already have sotorasib [Lumakras]. In terms of any new signals with adagrasib compared to sotorasib, activity seems like it might be comparable. So it’s another option. Maybe a little bit of a different adverse event profile, slightly different, but we’ll see. But likely we’ll have two options to use in KRAS G12C-mutated non-small cell lung cancer here not too far down the road.

The other thing, looking at posters today, we heard a lot about antibody drug conjugates in non-small cell lung cancer. Some of the interesting ones were patritumab deruxtecan, which targets HER3, but a poster presented today showed the activity of this drug in an unselected, non-small cell lung cancer patient population that did not have activating EGFR mutations where we already know that this drug has some activity.

So nice to see a response rate of just over 40% in unselected lung cancer with this targeted therapy.

Another antibody drug conjugate [ADC] that we heard about in the poster session was telisotuzumab vedotin, which is a c-MET antibody drug conjugate. And this drug also looks to be active in patients with c-MET-overexpressing non-small cell lung cancer.

One poster described the trial looking at it in patients with EGFR mutations after failure of osimertinib [Tagrisso] in frontline therapy who have c-MET overexpression, definitely showed activity when this drug was added to osimertinib in tolerability.

And then also looking at the drug telisotuzumab on its own in c-MET overexpressing non-small cell lung cancer without EGFR mutations, also showing activity there that seem to be dependent on the level of c-MET expression. So another interesting ADC that looks like the target is predictive of its effect, and look forward to hearing more.