Halmos Highlights Immunotherapy Treatment Decisions, Emerging ADCs in NSCLC

Balazs Halmos, MD

For patients with non–small cell lung cancer (NSCLC) without driver mutations such as EGFR or ALK, immunotherapy-based regimens have become standard of care in the frontline setting. New data have continued to help shape treatment decisions based on PD-L1 expression, either with immunotherapy alone or in combination with chemotherapy, according to Balazs Halmos, MD.

Halmos also noted that additional data have helped guide toxicity management with these agents and combinations.

“Learning about how to use biomarkers properly, how to select patients for optimal treatment, and how to manage these patients with the safest monitoring and toxicity management is important,” Halmos said in an interview with OncLive^® at the 17th Annual New York Lung Cancers Symposium^® in New York, New York. Halmos served as co-chair for the event.

Halmos discussed the role of immunotherapy in the frontline setting of NSCLC and the emerging pipeline of antibody-drug conjugates (ADCs) that could affect the treatment paradigm in lung cancer. He is a professor of Medical Oncology in the Department of Oncology, a professor of Oncology and Hematology in the Department of Medicine, and the chief of Thoracic Oncology at Albert Einstein College of Medicine, Montefiore Medical Center.

OncLive^®: What were your favorite sessions at this year’s symposium?

Halmos: The New York Lung Cancers Symposium^® is my favorite lung [cancer] conference of the year. We had a fantastic day this year with not 1 or 2, but 4 different special sessions. One focused on the integration of perioperative treatments, neoadjuvant vs adjuvant, compared with a radiation-based definitive treatment program.

We had a special session on molecular pathology, looking at liquid biopsies, minimal residual disease testing, and expanded molecular testing. We had a practical session with experts discussing how to use different regimens in your patients. How do you decide up-front between chemo-immunotherapy vs immunotherapy? How do you manage toxicities? How do you manage patients with oligometastatic disease? We also had a special session focusing on molecularly targetable alterations given by fantastic experts.

[We also had] 8 different challenging case presentations by some of the best faculty around [New York].

What is the role of immunotherapy in the frontline setting for patients without key driver mutations?

Immune checkpoint inhibition has completely transformed the care of our patients with metastatic NSCLC, specifically for those without an actionable alteration, such as EGFR or ALK. [We are at the] point where almost all of our patients will receive immunotherapy in some shape or form, either single-agent immunotherapy, especially for biomarker selected patients with a high tumor proportion score [TPS], or different chemotherapy/immune-oncology combinations for other patients.

What has fam-trastuzumab deruxtecan-nxki (Enhertu) provided to patients with HER2-mutated NSCLC?

It has been exciting to see that we are moving away from the molecular-targeted TKIs and checkpoint inhibitors [for patients with HER2-mutated NSCLC]. We have a new class of molecules making a difference for our patients, and those are ADCs. Trastuzumab deruxtecan is a great example for a molecularly selected subset of patients with HER2 (ERBB2) exon 20 insertion mutations.

Trastuzumab deruxtecan showed excellent efficacy, with a [overall] response rate of 58% [in the phase 2 DESTINY-Lung02 trial (NCT04644237)] with durable responses, [leading to] FDA approval. [The approval] ensures that we are testing for this biomarker, and through the treatment continuum for patients, we are able to offer another effective treatment choice. This is a fantastic advance for our field and especially for these patients.

Are there any other intriguing ADCs under development in NSCLC that you are particularly excited about?

We need to pay attention to trastuzumab deruxtecan because there are many more [ADCs] coming, and we need to learn how to utilize these ADCs the best way for our patients. There are some unique toxicities with ADCs such as pneumonitis, ocular toxicities, or neuropathy with certain agents.

There are many ADCs showing a lot of excitement both in patients with EGFR mutations, such as patritumab deruxtecan [HER3-DXd], the anti-HER3 [ERBB3] antibody. [We are also investigating] anti-TROP2 antibodies for a broad selection of patients, anti-CEACAM5 antibodies, and anti-MET antibodies for MET-selected patients.

We now have a large spectrum of potential choices emerging. [It is important to] pay attention to these studies and accrue patients to them so we can learn [about these ADCs] faster. If we can utilize these agents appropriately for our patients, learning how to do that most effectively and safely will be important.

How have physicians used atezolizumab (Tagrisso) in this space?

Atezolizumab is one of our excellent checkpoint inhibitors. It is an anti–PD-L1 agent that is widely used for patients with extensive-stage small cell lung cancer based on the phase 3 IMpower133 trial [NCT02763579]. This remains the most commonly used agent in combination with carboplatin and etoposide, making a big difference for our patients.

[In NSCLC], atezolizumab is approved, and…used for both biomarker positive and high TPS patients as a single-agent immunotherapy, as well as a combination regimen, based on the Impower series of studies for advanced NSCLC, without TPS selection, necessarily.