Study results show no increase in progression-free survival with combination treatment of osimertinib and bevacizumab compared with osimertinib alone for patients with advanced lung adenocarcinoma and an EGFR T790M mutation.
Several studies of first-generation EGFR tyrosine kinase inhibitors (TKIs) showed that dual treatment with an EGFR-TKI and an angiogenic inhibitor had potential as a treatment strategy for patients with EGFR-mutated lung adenocarcinoma. In particular, a preclinical study showed that a dual EGFR-TKI + angiogenic inhibitor treatment strategy presented promising results in an EGFR T790M–mutated model. Based on these initial studies, the authors sought to test the efficacy and safety of dual bevacizumab + osimertinib treatment in patients with EGFR T790M–mutated advanced lung adenocarcinoma. They presented the results during the ESMO Virtual Congress 2020.
Patients with advanced lung adenocarcinoma and an EGFR T790M mutation treated with a first- or second-generation EGFR-TKI were randomized 1:1 to receive osimertinib (80 mg daily; N = 41) or osimertinib + bevacizumab (15 mg/kg divided every 3 weeks; N = 81). The primary end point was progression-free survival (PFS); the secondary end points were overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), and safety. The authors hypothesized a 0.55 improvement in PFS in the osimertinib + bevacizumab cohort compared with osimertinib alone. To achieve this, ≥80 patients were needed to provide an 80% power and a 20% 2-sided significance.
The median age of patients was 68 years (range, 41-82 years), 41% were male, 7% had stage III cancer, 70% had stage IV cancer, 22% had a cancer recurrence, 46% had a performance status of 0, 54% had a performance status of 1, 26% had brain metastasis, and 21% had a history of cytotoxic chemotherapy.
The median PFS was 9.4 months for the osimertinib + bevacizumab arm compared with 13.5 months for osimertinib alone (hazard ratio [HR], 1.44; 95% confidence interval, 1.00-2.08; P = .20). The median TTF was 8.4 months for the osimertinib + bevacizumab arm compared with 11.2 months for osimertinib alone (HR, 1.54; P = .12). The osimertinib + bevacizumab arm did not reach a median OS, whereas the osimertinib-alone arm had a median OS of 22.1 months (P = .96). The ORR was 68% for the osimertinib + bevacizumab arm and 54% for the osimertinib-alone arm. The most common adverse events with a grade ≥3 rating for the osimertinib + bevacizumab arm were proteinuria (23%), hypertension (20%), and infection (10%).
The authors concluded that the dual treatment of osimertinib + bevacizumab for patients with advanced lung adenocarcinoma and an EGFR T790M mutation did not show increased PFS compared with osimertinib alone.
Toi Y, et al. ESMO 2020. Abstract 1259O.