Acquired resistance to TKI is an important unmet need in the management of metastatic EGFR-mutated lung cancer. The current trial examined the efficacy of combinational approach with VEGF inhibitor, check point inhibitor immunotherapy and platinum-based chemotherapy in an Asian cohort.
Metastatic EGFR mutated NSCLC patients who failed at least one TKI were recruited. For those with T790M mutation, radiological progression on osimertinib was required for enrollment. Patients were treated with combination regimen of atezolizumab (1200mg), bevacizumab (7.5mg/kg), pemetrexed (500mg/m2) and carboplatin (AUC 5) once every 3 weeks until progression. Endpoints were objective response rate (ORR), progression free survival (PFS) and overall survival (OS).
Forty patients were enrolled with median age of 62. More than half (57.5%) had progressed on osimertinib. Stable brain metastases were present in 22.5% at baseline. PD-L1 expression was <1% in 52.5%. Median follow-up time was 11.0 months. ORR was 62.5%. Median PFS was 9.43 month (95% CI: 7.62 – 12.1 months). Among the 31 patients who progressed on the clinical trial treatment, 11 of these had CNS being the only site of progression. Median OS was not mature yet and the 1-year OS rate was 72.5%. Treatment related grade 3 or above adverse events (AE) occurred in 37.5% (15/40) and led to 1 discontinuation (2.5%), 7 dose interruption (17.5%) and 1 death (2.5%, myocardial infarct). Grade 2 hypertension developed in 27.5% of patients. Two patients developed asymptomatic pulmonary embolism and one patient deep vein thrombosis. All these three patients were able to resume clinical trial treatment after treatment. Immune-related AE occurred in 32.5% (13/40). All were grade 1-2 moderate hypo/hyperthyroidism and adrenal insufficiency except 2 patients who developed transient grade 3 liver transaminase increase and grade 4 poly-neuropathy.
Combination approach of atezolizumab, bevacizumab, pemetrexed and carboplatin achieved promising efficacy in metastatic EGFR-mutated NSCLC after TKI failure. The results were comparable with taxane based combinational approach. Most of the adverse events were moderate and manageable.
NCT03647956.
The authors.
F. Hoffmann-La Roche AG.
T.C. Lam: Advisory/Consultancy: Roche Diagnostics; Research grant/Funding (institution): Mundipharma; Research grant/Funding (institution): Pfizer. V.H.F. Lee, K.O. Lam: Research grant/Funding (institution): MSD. C.L. Chiang: Research grant/Funding (self): Merck; Research grant/Funding (self): BMS. All other authors have declared no conflicts of interest.