In a Chinese phase III trial (OptiTROP-Lung-04) reported at the recent ESMO Congress and published in The New England Journal of Medicine, Fang et al found that monotherapy with sacituzumab tirumotecan (sac-TMT)—an antibody-drug conjugate targeting trophoblast cell–surface antigen 2—was associated with better progression-free survival and overall survival vs platinum-based chemotherapy in patients with EGFR-mutated locally advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) progressing after EGFR tyrosine kinase inhibitor therapy.
In an interim analysis of progression-free survival, sac-TMT monotherapy met the prespecified criterion for significance vs chemotherapy (P < .0001).
Study Details
In the open-label multicenter trial, 376 patients were randomly assigned between July 2023 and April 2024 to receive sac-TMT at 5 mg/kg on days 1 and 15 of 28-day cycles (n = 188) or chemotherapy (n = 188). Chemotherapy consisted of pemetrexed at 500 mg/m2 plus investigator’s choice of carboplatin at AUC of 5 or cisplatin at 75 mg/m2 on day 1 of up to four 21-day cycles, followed by pemetrexed maintenance. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival as assessed by blinded independent review. The current report presents the final analysis of progression-free survival and preplanned interim analysis of overall survival.
Key Findings
After a median follow-up of 18.9 months, median progression-free survival was 8.3 months (95% confidence interval [CI] = 6.7–9.9 months) in the sac-TMT group vs 4.3 months (95% CI = 4.2–5.5 months) in the chemotherapy group (hazard ratio [HR] = 0.49, 95% CI = 0.39–0.62). The rate at 12 months was 32.3% vs 7.9%.
At an interim analysis of overall survival, death had occurred in 67 patients in the sac-TMT group vs 101 patients in the chemotherapy group (HR = 0.60, 95% CI = 0.44–0.82, P = .001). Median overall survival was not evaluable (95% CI = 21.5 months to not evaluable) in the sac-TMT group vs 17.4 months (95% CI = 15.7–20.4 months) in the chemotherapy group; the rate at 18 months was 65.8% vs 48.0%.
The median duration of treatment was 9.6 months in the sac-TMT group and 4.9 months in the chemotherapy group. Grade ≥ 3 treatment-related adverse events occurred in 58.0% of the sac-TMT group vs 53.8% of the chemotherapy group; the most common adverse events in both groups were decreased neutrophils (39.9% vs 33.0%) and decreased white blood cells (27.7% vs 22.0%). Treatment-related serious adverse events were reported in 9.0% vs 17.6% of patients. Treatment-related death occurred in one patient in the chemotherapy group, due to cardiorespiratory arrest.
The investigators concluded: “In patients with EGFR-mutated advanced or metastatic NSCLC that had progressed after previous EGFR-TKI therapy, progression-free survival and overall survival outcomes were significantly better with sac-TMT than with platinum-based chemotherapy.”
Wenfeng Fang, MD, of Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, and Junyou Ge, PhD, of National Engineering Research Center of Targeted Biologics, Chengdu, are two of the corresponding authors for The New England Journal of Medicine article.
Disclosure: The study was funded by Sichuan Kelun-Biotech Biopharmaceutical. For full disclosures of all study authors, visit nejm.org.
