Stephen Liu, MD, chief of hematology and oncology at Georgetown University, discusses the phase 3 DESTINY-Lung04 trial of first-line trastuzumab deruxtecan in HER2-mutant non–small cell lung cancer. He highlights the improvement in progression-free survival over chemoimmunotherapy, the early and crossover-confounded overall survival analysis, and the importance of weighing interstitial lung disease risk when choosing among emerging first-line options.
Transcript:
Dr. Liu: Hi, my name is Dr. Stephen Liu. I’m the chief of hematology and oncology at Georgetown University.
What does DESTINY-Lung04 add to our understanding of first-line treatment for HER2-mutated NSCLC?
Dr. Liu: DESTINY-Lung04 is a phase 3 study looking at frontline trastuzumab deruxtecan, a HER2 antibody-drug conjugate with a topoisomerase I payload. And as many of us expected, it was superior to chemoimmunotherapy, meeting its endpoint of progression-free survival improvement. And I would expect this leads to its availability in the frontline setting.
But there were some important points about DESTINY-Lung04. One was really the lack of difference in survival. It’s very early, yes, and with high crossover both to T-DXd and other HER2-directed therapies, it’ll make that a little cloudy. We’ll need to use different analyses to really look at the impact of crossover. I think it’s clear that this is a very active drug, that the progression-free survival is very impressive.
But one lingering concern from DL4 really was the interstitial lung disease and that rate north of 20% caught a lot of our attention. It’s a little higher than we’d seen in the later-line settings. It’s not so different, and I think the caveat that many of these were elevated to grade 2 because of steroid use is very valid. I’m comfortable with using the drug, but when we have other frontline options such as TKIs, does this sort of shift the preference to that, knowing that that ILD risk is there?