Halmos highlights immunotherapy treatment decisions and emerging ADCs in NSCLC

Balazs Halmos, MD, discusses the role of immunotherapy in the first-line treatment of NSCLC and the emerging pipeline of antibody-drug conjugates that could transform the lung cancer treatment paradigm.

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

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

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

Halmos discussed the role of immunotherapy in the first-line treatment of NSCLC and the emerging pipeline of antibody-drug conjugates (ADCs) that could transform the lung cancer treatment paradigm. He is Professor of Medical Oncology in the Department of Oncology, Professor of Oncology and Hematology in the Department of Medicine, and 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 Cancer 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, versus a radiation-based definitive treatment program.

We had a dedicated molecular pathology session where we looked at liquid biopsies, minimal residual disease testing and advanced molecular testing. We had a hands-on session with experts where we discussed how to use different therapies on your patients. How do you decide in advance between chemo-immunotherapy and immunotherapy? How do you deal with toxicities? How do you treat patients with oligometastatic disease? We also had a special session focused on molecular targeted changes given by fantastic experts.

[We also had] 8 different challenging case presentations from some of the best faculty in the world [New York].

What role does immunotherapy play in the frontline setting for patients without key driver mutations?

Immune checkpoint inhibition has completely transformed the care of our patients with metastatic NSCLC, particularly for patients with no actionable change, such as: EGFR or ALK. [We are at the] Point at which almost all of our patients are receiving some form of immunotherapy, either single agent immunotherapy, particularly for biomarker-selected patients with a high tumor fraction [TPS]or other chemotherapy/immuno-oncology combinations for other patients.

What has fam-trastuzumab deruxtecan-nxki (Enhertu) provided for patients? HER2-mutant NSCLC?

It’s been exciting to see us moving away from molecularly targeted TKIs and checkpoint inhibitors [for patients with HER2-mutated NSCLC]. We have a new class of molecules that are making a difference to our patients and they are ADCs. Trastuzumab deruxtecan is an excellent example of a molecularly selected subset of patients with HER2 (ERBB2) exon 20 insertion mutations.

Trastuzumab-deruxtecan showed excellent efficacy, with a [overall] 58% response rate [in the phase 2 DESTINY-Lung02 trial (NCT04644237)] with permanent answers, [leading to] FDA approval. [The approval] ensures we test for this biomarker and by continuing to treat patients we can offer another effective treatment option. This is fantastic progress for our field and especially for these patients.

Are there any other exciting ADCs being developed in NSCLC that you’re particularly excited about?

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

There are many ADCs that show both in patients with a lot of excitement EGFR Mutations such as paritumab deruxtecan [HER3-DXd]the anti-HER3 [ERBB3] Antibody. [We are also investigating] Anti-TROP2 antibodies for a wide range of patients, anti-CEACAM5 antibodies and anti-MET antibodies for MET-selected patients.

We now have a wide spectrum of possible choices emerging. [It is important to] Pay attention to these studies and attract patients to them so we can learn [about these ADCs] More quickly. If we can use these agents appropriately for our patients, it is important to learn how to do so most effectively and safely.

How have doctors used atezolizumab (Tagrisso) in this area?

Atezolizumab is one of our outstanding checkpoint inhibitors. It is an anti-PD-L1 compound that is widely used in patients with advanced small cell lung cancer based on the phase 3 IMpower133 study [NCT02763579]. This remains the most commonly used agent in combination with carboplatin and etoposide, making a huge difference to our patients.

[In NSCLC]Atezolizumab is approved and used in both biomarker positive and high TPS patients as single agent immunotherapy and as combination therapy based on the Impower series of studies in advanced NSCLC, necessarily without TPS selection.

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