Lyudmila A. Bazhenova, MD

With the integration of neoadjuvant, adjuvant and perioperative chemoimmunotherapy approaches into the nonsmall 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.

Its 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.

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 its hard to apply these data to current practice. However, it is important to be aware of what agents are coming down the lineonce they are FDA approved, we can utilize that treatment modality.

Its 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.

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 clinicians] institution is appropriate. At UCSD, we are believers in neoadjuvant and perioperative immunotherapy, so thats what we offer our patients. Again, like with unresectable disease, multidisciplinary care is vital. Clinicians should make sure to discuss [the patients 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.

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 theyre 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.

At UCSD, we have the [phase 2 TRUST-II study (NCT04919811)] with taletrectinib for ROS1rearranged 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).

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. Its 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 didnt 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 dont miss patients who display oncogenic drivers.

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