Several promising advances in the treatment of non-small cell lung cancer (NSCLC) were presented at the 2024 World Conference on Lung Cancer, showcasing novel therapies and treatment strategies that could improve patient outcomes. Researchers from MD Anderson Cancer Center presented data on targeted therapies, immunotherapy combinations, and novel inhibitors, offering new hope for patients with various subtypes of NSCLC.
Perioperative Durvalumab Improves Outcomes in Resectable NSCLC
The Phase III AEGEAN trial demonstrated that adding durvalumab, an anti-PD-L1 immune checkpoint inhibitor, to perioperative chemotherapy significantly improved event-free survival (EFS) and pathological complete response (pCR) rates compared to chemotherapy alone in patients with resectable NSCLC. After 18 months of follow-up, the durvalumab arm showed a continued EFS benefit, with a 31% lower risk of disease progression compared to the control group after a median follow-up of 25.9 months. Based on these results, the FDA approved this regimen in August 2024 as a new standard of care for resectable NSCLC. John Heymach, M.D., Ph.D., led the research.
NeoCOAST-2 Study: TROP2 ADC Shows Promise in Neoadjuvant NSCLC
In the Phase II NeoCOAST-2 study, adding durvalumab to perioperative chemotherapy in combination with either an anti-CD73 antibody, an anti-NKG2A antibody, or a TROP2 antibody-drug conjugate (ADC) was investigated in patients with resectable Stage IIA-IIIB NSCLC. The TROP2 ADC arm exhibited the highest major pathological response (mPR) and pCR rates, at 65.9% and 34.1%, respectively, suggesting the therapeutic potential of ADCs in the neoadjuvant setting. The treatments in all arms showed manageable safety profiles and surgical rates, comparable to current immunotherapy-based regimens. Tina Cascone, M.D., Ph.D., presented the updated data.
Oral HER2 Inhibitors Show Efficacy in HER2-Mutant NSCLC
BAY 2927088, an oral tyrosine kinase inhibitor targeting mutant HER2, was granted breakthrough therapy designation by the FDA for pretreated patients with unresectable HER2-mutant NSCLC. Updated results from the Phase I/II SOHO-01 study showed an objective response rate of 72.1%, including one complete response, in 44 patients with advanced HER2-mutant NSCLC. The median duration of response and progression-free survival were 8.7 months and 7.5 months, respectively. Xiuning Le, M.D., Ph.D., led the research, noting that 95.5% of patients experienced manageable drug-related side effects.
Zongertinib, another oral HER2-specific tyrosine kinase inhibitor, demonstrated promising efficacy in HER2-positive metastatic NSCLC. In the Phase Ia Beamion LUNG-1 trial, zongertinib achieved an objective response rate of 66.7% and a disease control rate of 95.5% in 132 pretreated patients with advanced HER2-positive metastatic NSCLC. The trial is ongoing, with manageable side effects reported. The FDA has granted zongertinib fast track designation for this patient population. John Heymach, M.D., Ph.D., presented these findings.
Firmonertinib Effective Against Rare EGFR Mutations
Firmonertinib, an oral, highly brain-penetrant EGFR inhibitor, was granted breakthrough therapy designation by the FDA for patients with advanced NSCLC harboring specific EGFR exon20 mutations. In the Phase I/II FURTHER study, firmonertinib showed an overall response rate of 81.9% at 240 mg and 47.8% at 160 mg in 60 patients with NSCLC harboring P-loop and aC-helix compressing (PACC) mutations. Among 13 patients with brain metastases, six (46.2%) achieved an objective response, highlighting the drug's ability to penetrate the blood-brain barrier. Xiuning Le, M.D., Ph.D., led the study, emphasizing the safety, efficacy, and antitumor activity of firmonertinib across a range of EGFR PACC mutations.
