Nathan A. Pennell, MD, PhD, discusses the evolution of targeting HER2 in lung cancer.

Nathan A. Pennell, MD, PhD,an associate professor in theDepartment of Medicine and director of the Lung Cancer Medical Oncology Program at theTaussig Cancer Institute of Cleveland Clinic,discusses the evolution of targeting HER2 in lung cancer.

HER2 is a target that has been around for a long time because it is used routinely in the treatment of patients with breast cancer, says Pennell. In lung cancer, it has beenrecognizedthatHER2mutations in the HER2 tyrosine kinase domain have been present in the disease for a long time; roughly2% of lung adenocarcinomas haveHER2mutations, adds Pennell.

Unfortunately, thecurrent data on targeting HER2 haveproven to bedisappointing, according to Pennell. TKIs that target EGFR and HER2, such as afatinib (Gilotrif), have had trials,but have demonstrated relatively marginal efficacy and an effect that is short lived. However, that seems to have changed recently with the emergence of the antibody-drug conjugates (ADCs).

ADCs have shown demonstrated promising efficacy in phase 2 trials withHER2-mutant lung cancer. Over the past few years,sometrials examining these agents in lung cancer have been presented at medical meetings.For example, findings froma phase 2 trialwithado-trastuzumab emtansine (Kadcyla; T-DM1) were reported,and this agent is already available for useinHER2-positive breast cancer.The agentwas examinedina cohort of patients withHER2-mutant lung cancerandwas found to elicit an impressive overall response rate of44%with a promising duration of control, says Pennell. This agent was probably used off label for HER2-positive lung cancer after these data were presented, Pennell adds.

Then, an oral presentation was delivered during the2020 ASCO Virtual Scientific Meetingon the phase 2 DESTINY-Lung01trial, which evaluated the ADC fam-trastuzumab deruxtecan-nxki (Enhertu) inHER2-mutated lung cancer. The agent showed an impressive response rate of 61.9%, which is comparable with what is expectedwith otherEGFR inhibitors inEGFR-mutant lung cancer.Trastuzumab deruxtecan also hadan estimated progression-free survival of 14 months. For the first time,the field is starting to see targeted drugs for this patient population that mirror targeted drugs that have been developed for other molecular alterations in lung cancer, concludes Pennell.

Link:

Dr. Pennell on the Evolution of Targeting HER2 in Lung Cancer - OncLive