Multidisciplinary Collaboration and Molecular Testing Are Integral to Treatment Decision-Making in NSCLC

Lyudmila A. Bazhenova, MD

With the integration of neoadjuvant, adjuvant and perioperative chemoimmunotherapy approaches into the non–small cell lung cancer (NSCLC) treatment paradigm, it is increasingly vital for clinicians to accurately identify patients with unresectable disease displaying key oncogenic drivers, such as EGFR and ALK mutations, before deciding on a therapeutic approach, according to Lyudmila A. Bazhenova, MD.

“It’s important to highlight that [genetic] testing is necessary for patients [with unresectable lung cancer], and remember that the phase 3 PACIFIC trial [(NCT02125461) regimen] is the standard of care [SOC] right now in this space,” Bazhenova said regarding a recent OncLive® Institutional Perspectives in Cancer webinar on lung cancer, which she chaired.

In an interview with OncLive, Bazhenova, who is a medical oncologist and professor of medicine at the University of California San Diego (UCSD) Moores Cancer Center in California, expanded on key topics in lung cancer that were discussed by her colleagues at UCSD Health. This included key considerations when navigating the use of perioperative immunotherapy for patients with or without oncogenically-driven lung cancers, the importance of collaboration between oncologists and other specialists when deciding on a treatment plan, and the need for increased and earlier implementation of biomarker testing in all patients with lung cancer.

OncLive: What key developments have been observed in NSCLC over the past year?

Bazhenova: 2023 has been a very busy year in lung cancer and several important publications have been presented. Many [of the emerging agents presented] do not have FDA approvals yet, so it’s hard to apply these data to current practice. However, it is important to be aware of what agents are coming down the line—once they are FDA approved, we can utilize that treatment modality.

Regarding the presentation by Karen Yun, MD, what are key factors in the management of unresectable lung cancer?

It’s important to know which cancers are resectable and which are unresectable. It is very important to work with your multidisciplinary team to make that decision. [Clinicians should not] forget that durvalumab [Imfinzi] is the SOC for patients with unresectable disease. I would not consider durvalumab for patients with oncogenic drivers, especially EGFR and ALK mutations.

As per the presentation by Sandip P. Patel, MD, how might clinicians navigate the use of neoadjuvant, adjuvant, and perioperative therapies in non oncogenically-driven lung cancer?

The challenge with this approach is the fact that there is no consensus because we have options for our patients. You can give them adjuvant, neoadjuvant or perioperative immunotherapy. We do not have any randomized trials telling us what the right thing to do is, so whatever works [at a given clinician’s] institution is appropriate. At UCSD, we are believers in neoadjuvant and perioperative immunotherapy, so that’s what we offer our patients. Again, like with unresectable disease, multidisciplinary care is vital. Clinicians should make sure to discuss [the patient’s situation] with a radiation oncologist as well as surgeon and determine a treatment plan in the beginning once all the specialists have evaluated the patient.

What are some key differences regarding neoadjuvant vs adjuvant EGFR- and ALK-directed treatment strategies for patients with oncogenic drivers in lung cancer, according to the presentation given by Kathryn A. Gold, MD?

For patients with EGFR mutations and ALK rearrangements, we know that immunotherapy generally does not work very well. For those patients, I would not consider neoadjuvant chemoimmunotherapy or adjuvant immunotherapy. Those patients will generally go to surgery. One could consider neoadjuvant chemotherapy if they’re dealing with a stage III cancer where this approach would be appropriate. After the completion of neoadjuvant treatment, it is important to make sure that [clinicians] offer those patients adjuvant osimertinib [Tagrisso], which is currently FDA approved.

Although adjuvant alectinib [Alecensa] has not yet been FDA approved, the phase 3 ALINA trial [NCT03456076] is very important. I hope that adjuvant alectinib will eventually become an FDA-approved option. It is also important to make sure that clinicians test patients for those abnormalities; ideally, one would want to test patients before selecting a neoadjuvant approach because your decision depends on the presence or absence of given mutations.

What planned or ongoing trials in the lung cancer space are being conducted at your institution that you’d like to highlight?

At UCSD, we have the [phase 2 TRUST-II study (NCT04919811)] with taletrectinib for ROS1–rearranged lung cancer. The preliminary efficacy [data] showed a high response rate [with the agent] and responses appear to be durable. The interesting fact about taletrectinib is that it does not inhibit trkB. So the adverse effect profile is different, and in my opinion better, than the safety profile of entrectinib (Rozlytrek) and repotrectinib (Augtyro).

What main message would you like to convey to colleagues regarding recent developments in NSCLC?

My main message is biomarkers, biomarkers, biomarkers! [Clinicians should] make sure that patients are being tested for molecular abnormalities and should understand the difference between DNA testing and RNA testing. [We should understand] the additional benefit that RNA testing brings, especially for patients with gene fusions, which are common in lung cancer.

[Lastly], we need to know the issues surrounding cell-free DNA. It’s a great tool for patients, but approximately 30% of cell-free DNA tests will produce a false negative. If an oncologist performs a liquid biopsy and didn’t discover the mutation, it is not appropriate to stop there. We want to make sure that tissue next-generation sequencing is being performed so we don’t miss patients who display oncogenic drivers.