FDA Approval of First-Line Oral Therapy for HER2-Mutant NSCLC Enhances Patient Experience: Estelamari Rodriguez, MD, MPH

Last month, the FDA granted accelerated approval to zongertinib (Hernexeos; Boehringer Ingelheim Pharmaceuticals) for adults with unresectable or metastatic nonsquamous non–⁠small cell lung cancer (NSCLC) harboring HER2 (ERBB2) tyrosine kinase domain (TKD) activating mutations, as detected by an FDA-authorized test.

Based on data from the Beamion LUNG-1 trial, this approval makes zongertinib the first oral, once-daily tyrosine kinase inhibitor (TKI) for treatment-naive patients with HER2-mutant advanced NSCLC, demonstrating both clinical efficacy and a manageable safety profile.

In a recent interview with The American Journal of Managed Care^® (AJMC^®), Estelamari Rodriguez, MD, MPH, discussed the therapy’s significance in the NSCLC treatment landscape, emphasizing its safety and tolerability. She highlighted zongertinib’s potential to improve patient adherence and quality of life while also acknowledging barriers that may limit equitable access.

Rodriguez is the associate director of community outreach for thoracic oncology and assistant director of diversity, equity, and inclusion at the University of Miami Sylvester Comprehensive Cancer Center.

This transcript has been lightly edited for clarity.

AJMC: The FDA recently granted accelerated approval to zongertinib for adults with unresectable or metastatic non-squamous NSCLC whose tumors have HER2 TKD-activating mutations. How significant is this approval in the current NSCLC treatment landscape?

Rodriguez: It's very significant because it's the first oral drug approved in the frontline setting for HER2-positive lung cancer, which accounts for about 2% to 4% of all lung cancers. These patients tend to be younger, never smokers; a lot of them can present with brain metastases.

We've been looking for better, targeted options. Until this approval, we had to offer patients chemoimmunotherapy and then HER2-directed therapy. So, I think this is very meaningful, not only because it's in the first-line setting and you can start targeting the driver of disease from the beginning, but also because they show very striking responses of 76% as an initial response rate. That is really meaningful to patients, especially if they present with brain metastases.

AJMC: What should clinicians know about the safety and tolerability of this regimen?

Rodriguez: Zongertinib, like many other oral TKIs, is not technically like intravenous (IV) chemotherapy, but it does have some toxicity, which is very manageable. Most of the toxicity here is gastrointestinal (GI) toxicity, including diarrhea.

Patients need to be counseled and have medications at home to be able to manage this. However, the grade 3 diarrhea, the severe diarrhea, was at a very low rate. We have seen that most of these GI toxicity episodes are manageable with those supportive measures.

AJMC: How might the once-daily oral dosing schedule impact patient convenience, adherence, and quality of life?

Rodriguez: It's really critical. I mean, we're asking patients to take a drug for the rest of their lives because these drugs are continued until disease progression. Regarding time toxicity, once we establish that the patient is on the best-tolerated dose and there are no dose adjustments, some of these patients come every 3 months to the clinic. That is very important for adherence, and it is very important for the quality of life of the patient in terms of not having to come to a cancer center.

That is really a game changer for these patients who are younger and in the part of their lives where they're still working and have children. Having a once-daily oral drug makes all of life for these patients better without really giving up on the benefits that you want to see about early responses, durable responses, and central nervous system activity.

AJMC: Are there any barriers, like financial, geographic, or insurance related, that could limit equitable access to this regimen? If so, what are they?

Rodriguez: In our current system, IV drugs are usually picked up by Medicare, for example, so you don't really have a big co-pay as a patient. However, this patient population, which is 2% to 4% of lung cancers, tends to be younger, so all of these patients, even with prior drugs, have had some challenges getting the drugs covered, even with traditional IV medication.

I think there are some challenges in terms of co-pay, but there are a lot of mechanisms in place to get patients co-pay assistance and foundations that can help cover the co-pays and voucher cards for those patients who are underinsured. But it is an important point, because with oral drugs, a lot of the cost falls on the patient with the co-pays, and we really have to be able to connect patients with those resources.