PACE-LUNG: A multicenter, single-arm, phase II clinical trial evaluating the efficacy of additional chemotherapy for patients with EGFRm NSCLC with the continued presence of plasma ctDNA EGFRm at week 3 after start of osimertinib first-line treatment (AIO-TRK-0422/ass)

PACE-LUNG

Patient / Population Intervention / Exposition Vergleich Endpunkt

In patients with EGFR-mutant advanced NSCLC and persistent ctDNA EGFRm after 3 weeks of first-line osimertinib, adding chemotherapy to osimertinib was feasible and was followed by a median progression-free survival of 16.3 months from start of chemotherapy.

N

50Patienten

Design

Academic multicentre, single-arm, investigator-initiated phase II trial in patients with untreated advanced/metastatic EGFR-mutant NSCLC and persistent plasma ctDNA EGFRm by Guardant360 after 3 weeks of osimertinib monotherapy, who received 4 cycles of additional chemotherapy followed by osimertinib maintenance (EudraCT 2019-004757-88).

Endpunkt

Investigator-assessed progression-free survival per RECIST 1.1 from start of chemotherapy (PFS1).

ErgebnisOf 255 patients screened, 74 (29%) had persistent ctDNA EGFRm after 3 weeks of osimertinib and 50 received additional chemotherapy. Median PFS1 was 16.3 months (95% CI 10.8-18.9), with 57.8% (42.0-70.6) and 21.7% (10.2-36.1) progression-free and alive at 12 and 24 months after start of chemotherapy. Median PFS0 from start of osimertinib was 17.8 months (12.9-20.5). Median OS1 was 29.2 months (95% CI 23.2-42.4), with 87.4% (74.1-94.2) and 65.4% (48.0-78.2) alive at 12 and 24 months. No new safety signals were observed.

Sebastian M, Wiesweg M, Alt J, et al. Presented at ESMO Congress 2026, abstract LBA73, 24 October. Not yet published.

Diskussion & Kritik

PACE-LUNG shows that selecting patients by persistent ctDNA EGFRm at week 3 and then adding chemotherapy is feasible across multiple centres. With a single arm and only 50 treated patients, there is no concurrent control: the claim that PFS compares favourably rests on historical data, and investigator-assessed PFS with wide confidence intervals cannot establish benefit over continuing osimertinib alone. Only 50 of the 74 biomarker-positive patients received chemotherapy and the abstract does not explain why the rest did not, which raises the possibility of selection bias. Safety is reported only as no new safety signals, with no adverse event rates, and the chemotherapy regimen is not specified.