The 2024 World Conference on Lung Cancer (WCLC) in San Diego showcased significant advancements in the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), including novel perioperative strategies, tyrosine kinase inhibitors, bispecific antibodies, and antibody-drug conjugates (ADCs). Over 7,000 clinicians and scientists gathered to discuss these breakthroughs.
Resectable NSCLC: Perioperative Immunotherapy and ADCs
Perioperative strategies in resectable NSCLC are evolving, with recent trials highlighting the prognostic potential of pathologic complete response (pCR). Patrick M. Forde, MBBCh, PhD, and colleagues presented an analysis of CheckMate 77T and CheckMate 816 data, demonstrating that perioperative nivolumab provides superior event-free survival improvement compared to neoadjuvant nivolumab (HR = 0.59; 95% CI = 0.38–0.92). This benefit was observed even in patients with PD-L1–negative disease and those who did not achieve pCR, suggesting broad applicability of postoperative immune checkpoint inhibition.
Tina Cascone, MD, PhD, and colleagues reported preliminary data from the NeoCOAST-2 study, evaluating neoadjuvant durvalumab with chemotherapy and novel agents, including datopotamab deruxtecan (Dato-DXd), a TROP2-directed ADC. The Dato-DXd arm showed major pathologic response and pCR rates of 65.9% and 34.1%, respectively, with high rates even in PD-L1–negative patients (58.3% and 25.0%, respectively), indicating the promise of integrating ADCs into localized NSCLC treatment.
Advanced NSCLC: EGFR and HER2 Targeted Therapies
In advanced NSCLC with EGFR mutations, the MARIPOSA trial's extended follow-up, presented by Shirish M. Gadgeel, MD, revealed that amivantamab/lazertinib significantly improved overall survival compared to osimertinib (HR = 0.77; 95% CI = 0.61–0.96; P = .019). Median overall survival was not reached for the combination therapy versus 37.3 months for osimertinib. Intracranial progression-free survival also favored amivantamab/lazertinib.
Jin-Ji Yang, MD, and colleagues reported results from the CTONG 2008 FLOWERS phase II trial in patients with de novo MET-aberrant and EGFR-mutant advanced NSCLC. The combination of osimertinib and savolitinib yielded a confirmed objective response rate of 90.5% (95% CI = 69.6%–98.8%) and a median progression-free survival of 19.6 months (95% CI = 10.2 months to not evaluable), compared to 60.9% (95% CI = 38.5%–80.3%) and 9.3 months (95% CI = 7.4 months to not evaluable) with osimertinib alone.
David Planchard, MD, PhD, presented preliminary data from the FURTHER phase Ib study of firmonertinib in treatment-naive patients with EGFR PACC mutations. Responses were observed across a range of PACC mutations, with a CNS objective response rate of 46.2% in patients with brain metastases.
Xiuning Le, MD, PhD, presented data from the SOHO-01 trial, where BAY 2927088, a reversible oral tyrosine kinase inhibitor, demonstrated an objective response rate of 72.1% (95% CI = 56.3%–84.7%) in HER2-mutant NSCLC patients naive to HER2-targeted therapy. Median duration of response and progression-free survival were 8.7 months (95% CI = 4.5 months to not evaluable) and 7.5 months (95% CI = 4.4–12.2 months), respectively.
Gerrina Ruiter, MD, PhD, shared results from the Beamion LUNG-1 phase Ia/Ib study of zongertinib in HER2-mutated NSCLC. The confirmed objective response rate was 95.5%, with 69.7% achieving a partial response. Grade ≥ 3 adverse events were reported in 18.2% of patients.
Advanced NSCLC: First-Line Immunotherapy and ADCs
Caicun Zhou, MD, PhD, and colleagues presented the HARMONi-2 phase III study, comparing ivonescimab, a bispecific antibody against PD-1 and VEGF, to pembrolizumab as first-line treatment for PD-L1–positive advanced NSCLC. Ivonescimab significantly prolonged median progression-free survival (11.1 months vs 5.8 months; HR = 0.51; 95% CI = 0.38–0.69; P < .0001).
Benjamin Besse, MD, PhD, presented the CARMEN-LC03 trial results, which showed similar median progression-free survival and overall survival between tusamitamab ravtansine and docetaxel in previously treated patients with CEACAM5-expressing advanced nonsquamous NSCLC.
Jacob M. Sands, MD, and colleagues reported updated data from the TROPION-Lung01 study, comparing datopotamab deruxtecan (Dato-DXd) to docetaxel. While median overall survival was not statistically different overall, a clinically meaningful trend was observed in the nonsquamous subgroup (14.6 months with Dato-DXd vs 12.3 months with docetaxel; HR = 0.84; 95% CI = 0.68–1.05).
Marina Chiara Garassino, MD, and colleagues presented data on TROP2 target expression and its correlation with response to Dato-DXd in the TROPION-Lung01 trial. Higher TROP2 expression was associated with improved objective response rate and longer progression-free survival with Dato-DXd compared to docetaxel.
SCLC: Antibody-Drug Conjugates
Charles M. Rudin, MD, PhD, presented the phase II IDeate-Lung01 trial of ifinatamab deruxtecan (I-DXd), an ADC targeting B7-H3, in previously treated extensive-stage SCLC. The objective response rate with I-DXd at 12 mg/kg was approximately twice that with I-DXd at 8 mg/kg (52.4% vs 26.1%).
