A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy
Mené au Japon sur 55 patients atteints d'un cancer du poumon non à petites cellules EGFR+, cet essai multicentrique de phase II évalue l'efficacité, du point de vue du taux de réponse, de l'osimertinib après l'échec d'un traitement combinant inhibiteurs de tyrosine kinase de première ou deuxième génération et chimiothérapie à base de sels de platine
Background: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non–small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan. Methods: We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer). Results: From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1%; 95% CI, 17.6–42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1%), and progressive disease, in 18 (32.7%). The median length of progression-free survival (PFS) was 4.07 months (95% CI 2.10–4.30), and the rate of 12-month PFS was 17.3%. Conclusions: Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.