Tumor Treating Fields therapy could potentiate immunotherapy in non-small-cell lung cancer
Mené entre 2017 et 2021 sur 276 patients atteints d'un cancer du poumon métastatique non à petites cellules (âge médian : 64 ans ; durée médiane de suivi : 10,6 mois ; 64 % d'hommes), cet essai randomisé international de phase III évalue l'intérêt, du point de vue de la survie globale, d'ajouter une thérapie utilisant des champs électriques "Tumor Treating Fields" au traitement systémique standard
Résumé en anglais
The use of systemic therapy for patients with stage IIIB or IV non-small-cell lung cancer has, in general, evolved rapidly over the past two decades. However, somewhat paradoxically, in 2023, for most patients with non-oncogene-addicted, relapsed non-small-cell lung cancer, treatment options have changed little since the introduction of docetaxel around the turn of the century.
Tumor Treating Fields (TTFields) is a non-invasive therapeutic method that has so far had clinical success, with US Food and Drug Administration approvals for the treatment of glioblastoma multiforme1 and mesothelioma2 when combined with chemotherapy. TTFields relies on the generation of an alternating current that disrupts mitotic spindle assembly,3 and has been reported to trigger adaptive immunity.4
In The Lancet Oncology, Ticiana Leal and colleagues5 report positive results from the pivotal phase 3 LUNAR clinical trial comparing TTFields therapy with investigator's choice of standard systemic therapy (a PD-1/PD-L1 immune checkpoint inhibitor6, 7, 8 or docetaxel) with systemic therapy alone in patients with metastatic non-small-cell lung cancer who had progressed on or after platinum-based therapy. 276 patients (median age 64 years [IQR 59–70, 178 [65%] male) were enrolled and randomly assigned to treatment. An overall acceptable level of toxicity was achieved, although the rate of serious adverse events was notably higher for TTFields with standard therapy (70 [53%] of 133 patients) compared with standard therapy alone (51 [38%] of 134). In a subgroup analysis, median overall survival was increased by 7·7 months with immune checkpoint inhibitor plus TTFields versus immune checkpoint inhibitor alone, consistent with preclinical findings that predicted an augmentation of immune checkpoint inhibitor-induced adaptive immunity, through TTFields-induced cGAS-STING and AIM2 inflammasome activation.4
Conversely, no significant improvement in median overall survival was seen for the docetaxel subgroup, in which the hazard ratio confidence limits crossed unity. A possible explanation is the respective pharmacodynamics of TTFields and docetaxel. Both induce the spindle assembly checkpoint,3 and, as such, adaptive resistance might be expected to limit both treatments simultaneously and equally, resulting in no prolonged clinical benefit for this combination.
