Final OS analysis of sacituzumab tirumotecan (sac-TMT) versus platinum-based chemotherapy in EGFR-mutated non-small cell lung cancer (NSCLC) after progression on EGFR-TKI: Phase III OptiTROP-Lung04 study

OptiTROP-Lung04

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with advanced EGFR-mutated NSCLC after progression on EGFR-TKI therapy, sacituzumab tirumotecan improved overall survival at the final analysis compared with pemetrexed plus platinum chemotherapy.

N

376Patienten

Design

Phase III trial randomising 376 patients 1:1 with locally advanced or metastatic EGFR-mutated NSCLC that had progressed on EGFR-TKI therapy to sacituzumab tirumotecan monotherapy or pemetrexed plus platinum followed by maintenance pemetrexed (NCT05870319).

Endpunkt

The abstract does not state the primary endpoint. Overall survival was a key secondary endpoint, and this is the prespecified final OS analysis.

ErgebnisAt a median follow-up of 32.3 months, median OS was 25.9 months (95% CI 22.2-27.5) with sacituzumab tirumotecan vs 17.4 months (95% CI 15.7-20.3) with chemotherapy (HR 0.69, 95% CI 0.54-0.89; nominal one-sided p=0.0021). OS rates were 54.1% vs 37.2% at 24 months and 40.5% vs 28.4% at 30 months. Subsequent ADC therapy was received by 22.6% of patients in the chemotherapy group. After RPSFT adjustment for subsequent ADC therapy, median OS was 25.9 vs 16.6 months (HR 0.57, 95% CI 0.42-0.75). No new safety signals emerged with extended follow-up.

Zhang L, Fang WF, Wu L, et al. Presented at ESMO Congress 2026, abstract LBA67, 25 October. Not yet published.

Diskussion & Kritik

With a median follow-up of 32.3 months, this final analysis shows that the overall survival benefit seen at the interim analysis held up, a hard endpoint in a randomised phase III trial. The p value is nominal because significance was already declared at the interim analysis. The RPSFT adjustment for the 22.6% of chemotherapy patients who later received an ADC depends on modelling assumptions and should be read as supportive. The abstract does not state the primary endpoint, gives no PFS figures, does not say whether the trial was blinded and offers no safety data beyond saying there were no new signals.