Stephen Liu, MD, on Key Debates in NSCLC

Stephen V. Liu, MD, of the Georgetown University School of Medicine and Georgetown’s Lombardi Comprehensive Cancer Center in Washington, DC, joined Lung Cancers Today to discuss key ongoing debates and questions related to non–small cell lung cancer (NSCLC).

“When we think of the ongoing debates in lung cancer, I think we can notice a theme,” Dr. Liu explained. “The theme is, are we delivering the right treatments to every patient?”

He explained that although the field has made advances in identifying certain subsets of lung cancer and delivering targeted therapies to patients with tumors that harbor driver alterations, it’s important to recognize that the bigger question surrounds potential overtreatment of certain patients.

“When we look at our large studies, we can show that different combination treatments are improving outcomes for large populations, but they’re also adding cost, adding toxicity,” Dr. Liu said. “Is that cost and toxicity necessary for all patients?”

This question is particularly relevant when considering treatments for patients with EGFR-positive NSCLC, he explained. For example, 2 combination regimens have improved outcomes over tyrosine kinase inhibitor (TKI) therapy monotherapy. In FLAURA-2, adding chemotherapy to osimertinib improved profession-free-survival (PFS), and the MARIPOSA trial showed that amivantamab and lazertinib improved PFS and overall survival compared with osimertinib.

“Those improvements and outcomes certainly warrant these as new standards of care,” Dr. Liu said. “But does everyone derive that benefit? Can we identify the patients that don’t need that combination therapy to get the same outcomes?”

However, despite concerns about overtreatment in certain groups of patients, Dr. Liu explained that “there’s some hesitancy to pull back on treatment,” because “outcomes in lung cancer still have a lot of room for improvement.”

He also shared another example regarding perioperative therapy in the early-stage setting.

“We know that adding neoadjuvant immunotherapy—nivolumab in CheckMate-77T, pembrolizumab in KEYNOTE 671, durvalumab in the NEJM [New England Journal of Medicine]—that giving that immunotherapy with neoadjuvant chemotherapy improves pathologic CR [complete response], improves event-free survival,” Dr. Liu said. “And we saw with KEYNOTE-671, that translates to a survival benefit.”

However, it’s important to recognize that those regimens also include an adjuvant component, he said, explaining that although questions remain about the necessity of this approach for certain patients, it can be challenging to properly study this “without depriving patients who need that extra treatment to get that benefit.”

Dr. Liu concluded by explaining what could help address these questions about tailoring treatment to the needs of specific patients and avoiding overtreatment or undertreatment.

“To really move the field forward, we need more reliable, consistent biomarker studies,” he said. “These need to be shown in the ongoing trials and then applied in large global collaborations to try to spare patients cost, spare patients toxicity [by] focusing on giving people the treatment that they need but trying to avoid giving people treatment that that they don’t need.”