Reflex Molecular Testing May Enhance Targeted Therapy Benefit in Early-Stage Lung Cancer

Jobelle Baldonado, MD

Efforts to standardize and implement reflex testing for biomarkers in early-stage non–small cell lung cancer could allow for earlier identification of appropriate targeted therapies that may be used in treatment, thereby improving patient outcomes, according to Jobelle Baldonado, MD, who adds that it is important for surgical oncologists to stay up to date on the development of targeted agents in lung cancer so they can best treat patients presenting with recurrent disease.

“I’m glad to know that there are a lot of options for advanced-stage NSCLC these days. It’s no longer just standard chemotherapy or even just immunotherapy—now there are a lot of targeted therapies,” Baldonado said in an interview with OncLive® regarding a recent OncLive State of the Science Summit on lung cancer, which she chaired. “It’s a good time to be treated for lung cancer, and hopefully there will be even more options and even more durable results in the future.”

In the interview, Baldonado, who is a thoracic surgeon at Moffitt Cancer Center in Tampa, Florida, expanded on key topics in lung cancer that were discussed by herself and colleagues at the event. This included how imaging can best inform the selection of initial biopsy sites during tumor sampling; the continued development and evolving use of targeted therapies and antibody-drug conjugates (ADCs) in lung cancer; and the need to institutionalize the administration of molecular testing in early-stages to ensure patients with driver mutations can receive optimal treatment.

OncLive: What are your recommendations for obtaining sufficient tissue for lung cancer biopsy?

Baldonado: There’s no one-size-fits-all mentality in terms of how to select that first biopsy site [when obtaining a tissue sample]. It’s not always [best to use only] CT-guided needle biopsy, navigational bronchoscopy, or surgical biopsy. We must adapt to or look at the images and see what the patient is tolerant of before we decide on that first biopsy site because an unnecessary biopsy delays the diagnosis to the treatment pathway. My talk at the SOSS primarily centered on looking at the imaging [prior to selecting a method of tissue sampling] and making sure that we choose right, we choose carefully, and that we get the patient to the [correct] treatment right away.

How have efforts to personalize treatment approaches in NSCLC been aided by the emergence of targeted therapies?

The key updates started 2 or 3 years ago when the phase 3 ADAURA trial [NCT02511106] data was released. After that, a lot of other targeted therapies have come out for both early-stage and metastatic lung cancer. There are multiple EGFR-targeted [therapies, as well as ones targeting] ALK and KRAS [mutations]. We also have [new] ADCs that I’ve never even known about before this lecture—I’ve only heard about ADCs as I’m a surgeon not a medical oncologist. It was nice for me to learn what ADCs are and what they target. This [represents] the new era of personalized medicine that we’re talking about.

Referencing the presentations given by Andreas Saltos, MD, how have the use of ADCs and targeted therapies continued to evolve in HER2- and HER3-positive NSCLC?

Dr Saltos [described] the mechanism of action of ADCs and ran through all the trials [of these agents]. What stuck with me was the [data on the targeted therapy] trastuzumab [Herceptin]. That’s mainly because it used to be a main target in breast cancers, and now it’s [being investigated] for lung cancers too. It was quite amazing to have the research to back [the fact that] it’s [use is] not just limited to one disease but is expanding because of all this research. He talked about [other] new drugs, but I doubt that we will learn about them until [they make it to] a big trial.

I’m also just amazed that [ADCs are] something that we can potentially use for patients with HER2-positive lung cancer. [Other emerging ADCs] are all in early stages [of development], but it’s nice to know that there are options [coming down] the pipeline.

What are the advantages of pathologist-initiated reflex biomarker testing at Moffitt Cancer Center, as per the presentation by Theresa Boyle, MD, PhD?

In other departments at our institution it’s [potentially protocol], but at least in the Department of Thoracic Oncology, [we don’t yet have] a reflex testing [approach] and there’s no [standardization] for that [process]. What happens with us is whenever we [identify] a patient with lung cancer, it’s [typically] not stage 1; it is [instead a] higher stage [such as] stages IB, IIB, III, or anything above 4 cm. We also have studies now that support [the use of] targeted therapy for these relatively early lung cancers. What happens is that the surgeon would then order [biomarker] testing once they see the pathology report.

Dr. Boyle’s talk centered on the ideal [situation] which is to test for everything. What if you miss [a key biomarker]? What if you did not see the pathology report, and you missed [that the patients’ tumor] size qualifies them for testing for possible targeted therapy? Then the patient would have lost the chance to be treated with something else that they need. Reflex testing is the way to go and it should be adapted to most institutions, especially cancer institutions. Unfortunately, that’s not how it is yet at Moffitt Cancer Center, but with all these targeted therapies coming out, I hope that it will be institutionalized.

As discussed by George Simon, MD, FACP, FCCP, how do you navigate the selection of ALK inhibitors in lung cancer?

There was one patient that I had with brain metastases who [was treated with] alectinib [Alecensa], and still does well after 3 to 4 years. [However], it was nice to know that there are a lot of options other [than alectinib]. What stuck with me was that all these ALK inhibitors have very good penetration to the blood-brain barrier, so you could essentially choose any agent and still have good penetration. However, the adverse effects [AEs] vary from ALK inhibitor to ALK inhibitor, so you generally change the medication you give to that patient based on what comorbidities, symptoms, or AEs they currently have from it.

The other thing that stuck with me from that presentation was the phase 3 ALINA trial [NCT03456076] data. The ALINA trial was for patients with early-stage, resected lung cancer. [Patients were required to have] at least 4 cm tumors or any lymph node involvement. They tested the tumors for ALK rearrangements, and [treated patients with] either alectinib or standard-of-care therapy. Outcomes were better for those who received alectinib and that’s encouraging for all the patients who potentially have driver mutations. [This discussion] prompted me to download the paper [because] that’s one of the things that I can explore as a surgeon.

How might earlier testing impact the benefit derived from targeted therapies in NSCLC?

There’s a lot of hope that I can see with targeted therapies. We mainly talked about advanced lung cancers in the symposium, but for me, being a surgeon, I see a lot of [patients with] early-stage lung cancers. When I see them for follow up, it’s not a good feeling to see them have recurrent disease after [treatment with] a curative therapy. I can’t wait for the time [when] even early-stage [disease] can potentially be tested for targeted therapies, and I can’t wait to have data to support that. A lot of patients will benefit from targeted drugs, even if they have stage I disease.

What main message would you like to impart to your surgical colleagues based on this discussion?

We did not talk about neoadjuvant and adjuvant trials in the symposium, but that’s one more [research area] that’s gaining robust data in terms of treatment for resectable disease. As surgical specialists, we are concerned with [this topic] because we deal with resectable disease. We’re not so familiar with the targeted therapies for metastatic disease. At the same time, it’s nice for me to learn [about these agents] because my patients can get advanced lung cancer when they come in for follow-up. There’s 2 different [avenues for investigation] here: resectable and advanced disease. I’m happy to know that we’re not just limiting research to one or the other in the lung cancer space.