Radiotherapy-free pembrolizumab combined with chemotherapy for locally advanced non-small-cell lung cancer with PD-L1 tumour proportion score of 50% or higher (Evolution trial): a multicentre, single-arm, phase 2 study
Mené sur 21 patients atteints d'un cancer du poumon non à petites cellules non résécable, de stade localement avancé et surexprimant PD-L1 (score de proportion tumorale : égal ou supérieur à 50% ; âge médian : 73 ans), cet essai multicentrique de phase II évalue l'efficacité, du point de vue de la survie sans progression à 2 ans, et la toxicité d'un traitement combinant pembrolizumab et chimiothérapie à base de sels de platine
Background: The standard of care for unresectable, locally advanced non-small-cell lung cancer (NSCLC) is chemoradiotherapy followed by durvalumab. This study (Evolution trial WJOG11819L) aimed to evaluate the efficacy and safety of radiotherapy-free pembrolizumab and chemotherapy in patients with unresectable, locally advanced NSCLC with a PD-L1 tumour proportion score (TPS) of 50% or higher.
Methods: This prospective, multicentre, single-arm, phase 2 study was conducted in nine institutes in Japan. Inclusion criteria were age 20 years or older, histologically confirmed unresectable, locally advanced NSCLC with a PD-L1 TPS of 50% or higher, an Eastern Cooperative Oncology Group performance status of 0 or 1, at least one measurable lesion, no previous systemic therapy, and adequate organ function. Patients received intravenous induction therapy comprising pembrolizumab 200 mg every 3 weeks plus platinum-based chemotherapy for four cycles: either cisplatin 75 mg/m2 or carboplatin (area under the curve [AUC] 5 for non-squamous NSCLC, AUC 6 for squamous NSCLC) plus pemetrexed 500 mg/m2 (non-squamous NSCLC) or nanoparticle albumin-bound paclitaxel 100 mg/m2 on days 1, 8, and 15 (squamous NSCLC). This was followed by maintenance therapy comprising intravenous pembrolizumab (200 mg) with or without intravenous pemetrexed (500 mg/m2) every 3 weeks for up to 2 years. The primary endpoint was 2-year progression-free survival and was assessed in the full analysis set (ie, all patients who met the eligibility criteria and received at least one dose of study treatment). The safety analysis set included all patients who received at least one dose of study treatment and had at least one post-treatment safety assessment. This trial was registered with ClinicalTrials.gov (NCT04153734) and is complete.
Findings: Between May 18, 2020, and Feb 22, 2022, 21 patients were assessed for eligibility and all were enrolled. Median age was 73 years (IQR 68–80); 16 (76%) patients were male; race and ethnicity data were not collected. Three (14%) patients discontinued and 18 (86%) patients completed the induction therapy; eight (38%) patients discontinued during maintenance therapy and ten (48%) patients completed the maintenance therapy. Median follow-up was 32·5 months (IQR 26·2–39·5). The 2-year progression-free survival rate was 67% (90% CI 46–83). The most common grade 3 or worse adverse events were neutropenia (eight [38%] of 21 patients), leukopenia (four [19%]), and pneumonia (three [14%]). Serious adverse events occurred in seven (33%) patients. No treatment-related deaths were reported.
Interpretation: These findings suggest that pembrolizumab combined with platinum-based chemotherapy, without radiotherapy, might provide a feasible and promising alternative treatment strategy for patients with unresectable, locally advanced NSCLC with a PD-L1 TPS of 50% or higher.
The Lancet Oncology , résumé, 2025