Targeted Therapies/Immunotherapy Have Made Promising Changes in NSCLC Treatment
Christine Bestvina, MD, stated that the presence of EGFR and ALK mutations can affect the way that a patient will react to treatment and should be factors that physicians consider.
Targeted therapies for EGFR and ALK mutations, as well as immunotherapy have evolved and adapted to the rapidly changing space of non–small cell lung cancer (NSCLC) treatment, according to Christine Bestvina, MD.
Bestvina, an associate professor of medicine at the University of Chicago, spoke with CancerNetwork® and indicated that recent neoadjuvant, adjuvant, and perioperative clinical trials—the phase 3 ADAURA trial (NCT02511106) evaluating osimertinib (Tagrisso) monotherapy in EGFR-mutated NSCLC and the phase 3 ALINA trial (NCT03456076) evaluating alectinib (Alecensa) compared with platinum-based chemotherapy in ALK-positive NSCLC, for example—have drastically improved targeted therapy treatment options. Now, physicians need to be testing patients for EGFR or ALK mutations, or even other targetable alterations, Bestvina said, because their presence can completely change the recommended type of immunotherapy.
Along with these new targeted therapies, physicians are also finding ways to combat problems like brain metastases. She mentioned the phase 3 CROWN trial (NCT03052608) that evaluated lorlatinib (Lorbrena) and crizotinib (Xalkori) in advanced ALK-positive lung cancer as a trial that was able to tame long term brain metastases.
Transcript:
The best way to highlight how EGFR and ALK mutations and immunotherapy have had an interplay currently [through] our patients who are surgically resectable. Previously, we had not regularly performed molecular testing for patients who had early-stage disease and were likely going to go to surgery. However, this perioperative space has dramatically improved over the past few years, with neoadjuvant, adjuvant, and perioperative immunotherapy clinical trials, as well as approvals for patients who have EGFR and ALK mutations in the adjuvant setting based on both [the] ADAURA[trial] and the ALINA trial.1,2 Given these approvals for both targeted therapies and immunotherapy, this has put a spotlight on the importance of molecular testing for patients with early-stage lung cancer, knowing that we do need to be testing patients for, at a minimum EGFR and ALK mutations, and potentially [utilizing] broader panels looking for targetable alterations, as it may alter the choice of immunotherapy.
Fortunately, we have a lot of data for systemic therapies and efficacy in the brain, which has allowed us to spare radiation for many patients. As an example for patients who have ALK mutations, we have the recent 5-year data from the CROWN study showing that the majority of patients who receive upfront lorlatinib (Lorbrena) with an ALK mutation remain intracranial progression-free even at 5 years. We’ve been able to spare radiation therapy, even [stereotactic radiosurgery] or targeted radiotherapy to the brain, for many of these patients, which I think has been increasingly important, recognizing that radio-necrosis can be a long-term complication of radiation to the brain. We’ve gotten much more comfortable watching small, asymptomatic brain metastasis while starting systemic therapy that we know has good [central nervous system] efficacy.
References
- FDA approves osimertinib as adjuvant therapy for non-small cell lung cancer with EGFR mutations. News release. FDA. December 18, 2020. Accessed February 3, 2025. https://tinyurl.com/y3csxmy9
- FDA approves alectinib as adjuvant treatment for ALK-positive non-small cell lung cancer. News release. FDA. April 18, 2024. Accessed February 3, 2025. https://tinyurl.com/2p8srv3p
