Treatment with sacituzumab tirumotecan (sac-TMT) significantly improves progression-free survival (PFS) and overall survival (OS) in patients with previously treated advanced EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) compared with docetaxel, according to the OptiTROP-Lung03 study presented at ELCC 2026.
In this updated analysis, as assessed by the investigator, a significantly higher PFS rate was observed with sac-TMT compared with docetaxel (72 percent vs 46 percent; hazard ratio [HR],0.23), which corresponded to a 77-percent reduction in the risk of disease progression or death.
Patients treated with sac-TMT also achieved a longer median PFS (7.9 vs 2.8 months), with a higher 12-month PFS rate (30.2 percent vs 2.2 percent), than those treated with docetaxel.
After a median follow-up of 23.8 months, patients in the sac-TMT group continued to demonstrate a significantly higher OS rate than those in the docetaxel group (51 percent vs 33 percent; hazard ratio [HR], 0.63), translating to a 37-percent reduction in the risk of death. [ELCC 2026, abstract LBA4]
In addition, the median OS was longer in sac-TMT-treated patients than docetaxel-treated patients (20 vs 13.5 months), with a higher OS rate at 18 months (54.7 percent vs 34 percent).
After a prespecified crossover-adjusted OS analysis conducted using the RPSFT* model, 41 percent of patients in the docetaxel group who received sac-TMT as subsequent anticancer therapy achieved a significant improvement in OS than those in the docetaxel group, demonstrating a 55-percent reduction in the risk of death (HR, 0.45).
Moreover, the 18-month OS rate was significantly improved by 54.7 percent in the sac-TMT group compared with 9.1 percent in the docetaxel group, with a longer median OS (20 vs 11.2 months).
Of note, “sac-TMT is the first therapy to achieve long-term OS benefits in patients with advanced EGFRm NSCLC who have progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy,” according to Dr Yunpeng Yang from Sun Yat-sen University Cancer Center in Guangzhou, China.
The OptiTROP-Lung03 study included 137 patients with advanced EGFRm NSCLC who progressed after EGFR TKI and platinum-based chemotherapy. Participants were randomized in a 2:1 ratio to receive sac-TMT 5 mg/kg Q2W (n=91, median age 57 years) or docetaxel 75 mg/m2 Q3W (n=46, median age 55 years).
In terms of safety, grade ≥3 treatment-related adverse events (TRAEs) occurred at a lower rate in the sac-TMT group than in the docetaxel group (60.4 percent vs 73.9 percent), as did the serious TRAEs (20.9 percent vs 41.3 percent).
Yang noted that although the median duration of exposure was longer with sac-TMT compared with docetaxel (7.1 vs 2.8 months), the occurrences of grade ≥3 and serious TRAEs were much lower with sac-TMT. Furthermore, no TRAEs resulted in treatment discontinuation or deaths in the sac-TMT group.
New treatment option
Overall, sac-TMT continued to demonstrate clinically meaningful and statistically significant improvements in PFS and OS compared with docetaxel, maintaining a manageable safety profile with no new safety signals observed after a median follow-up of approximately 2 years, said Yang.
This final OS analysis from the OptiTROP-Lung03 study highlights sac-TMT as a promising new treatment option in this patient population, he added.
Based on the findings of the main OptiTROP-Lung04 study, sac-TMT has been recently approved by the China National Medical Products Administration as the first TROP2**-antibody-drug conjugate for the treatment of patients with EGFRm NSCLC following EGFR TKI therapy, Yang noted.