Abstract 12P
Background
Acquired resistance to EGFR TKI remains a significant barrier for patients with EGFR-mutated lung cancer, especially for those without acquired EGFRT790M. The current study explored the safety and efficacy of combinational treatment with atezolizumab, bevacizumab, and pemetrexed-platinum in patients with EGFR-mutated NSCLC after failure of EGFR TKIs.
Methods
NSCLC patients with activated EGFR mutations after failure of EGFR TKIs were recruited, and patients with T790M were excluded. The treatment is to combine atezolizumab, bevacizumab (7.5 mg/kg), and pemetrexed-platinum once every 3 weeks until progression. Endpoints were ORR, PFS, and OS. For comparison, we retrieved a historical control group that enrolled patients with EGFR mutations who received pemetrexed-platinum plus bevacizumab after failure of single using EGFR TKI from 2009 to 2020. This study is active and recruiting patients is still ongoing.
Results
Twenty patients were enrolled, and the median age was 62 years. Seven patients had taken osimertinib before enrollment. PD-L1 expression was ≧ 1% in 35.0%. The median follow-up time was 15.6 months. One patient was excluded from response analysis due to idiopathic thrombocytopenic purpura being diagnosed after 1st-cycle treatment. ORR was 42.1%, and the DCR was 100%. Median PFS was 10.2 months, and OS was not mature yet. Patients with PD-L1 ≧ 1% have a higher ORR than those with PD-L1 < 1% (85.7% vs. 16.7%; p = 0.003). Compared with the historical control group (Bev/Pem/Platin) (n = 53), the experimental treatment (Atezo/Bev/Pem/Platin) showed significant benefits in DCR (100.0% vs. 64.2%; p = 0.002) and PFS (10.2 vs. 5.9 mo.; p = 0.007). There were no significant differences in ORR (42.1% vs. 30.2%; p = 0.401) and OS (unmatured vs. 19.3 mo.; p = 0.134). Grade ≧ 3 adverse events occurred in 40.0% (8/20) patients, especially 2 venous thromboembolism, 1 hydrocephalus, and 1 renal abscess.
Conclusions
The combination treatment of atezolizumab, bevacizumab, and pemetrexed-platinum provided favorable efficacy in EGFR-mutated NSCLC after TKI failure. The DCR and PFS of pemetrexed-platinum plus bevacizumab could be improved by the addition of atezolizumab.
Clinical trial identification
NCT 04147351.
Legal entity responsible for the study
The authors.
Funding
Roche.
Disclosure
S. Wu: Financial Interests, Personal, Invited Speaker, speaking honoraria: Roche; Financial Interests, Personal, Invited Speaker, speaking honoraria: AstraZeneca; Financial Interests, Personal, Invited Speaker, speaking honoraria: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker, speaking honoraria: Novartis; Financial Interests, Personal, Invited Speaker, speaking honoraria: Eli Lilly; Financial Interests, Personal, Invited Speaker, speaking honoraria: MSD; Financial Interests, Personal, Invited Speaker, speaking honoraria: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, speaking honoraria: Chugai Pharmaceutical; Financial Interests, Personal, Other, travel expense: Roche; Financial Interests, Personal, Other, travel expense: Boehringer Ingelheim. C. Ho: Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Roche-Genentech; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceuticals; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Ono Pharmaceuticals. J.C. Yang: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche/Genentech; Financial Interests, Personal, Invited Speaker: Roche/Genentech; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: Clovis Oncology; Financial Interests, Personal, Invited Speaker: Clovis Oncology; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bayer. B. Liao: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. Y. Lin: Financial Interests, Personal, Invited Speaker: ACT Genomics; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Invited Speaker: Manudipharma; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: TTY Biopharm; Financial Interests, Personal, Other, travel expense: Pfizer. W. Liao: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Speaker’s Bureau: Eli Lilly; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Speaker’s Bureau: MSD Oncology; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Chugai Pharma Taiwan; Financial Interests, Personal, Speaker’s Bureau: Chugai Pharma Taiwan. J. Shih: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal, Advisory Board: Chugai Pharmaceutical; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Other, travel expense: Roche; Financial Interests, Personal, Other, travel expense: Pfizer; Financial Interests, Personal, Other, travel expense: MSD; Financial Interests, Personal, Other, travel expense: Chugai Pharmaceutical; Financial Interests, Personal, Other, travel expense: Bristol Myers Squibb. All other authors have declared no conflicts of interest.