The EPICAL trial, a phase Ib study combining first line afatinib with anti-EGF vaccination in EGFR-mutant metastatic
D Rodríguez-Abreu1, M Cobo2, S García-Román3
1Medical Oncology, Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain.
Introduction:
Combination of anti-EGFR monoclonal antibodies or immune checkpoint inhibitors with TKIs has shown minimal benefit in EGFR mutant (EGFR-mut) NSCLC patients. Consequently, new combination approaches are needed.
Patients And Methods:
The EPICAL was a single arm, phase 1b study to evaluate safety, tolerability and anti-tumor activity of first line afatinib combined with anti-EGF vaccination in advanced EGFR-mut patients. EGFR status and mutations in liquid biopsies were determined by reverse transcriptase-polymerase chain reaction; serum biomarkers by ELISA and Western blotting analysis.
Results:
The assay enrolled 23 patients, 21 completed the anti-EGF immunization phase. Treatment was well tolerated and no serious adverse events (SAEs) related to the anti-EGF vaccine were reported. Objective response and disease control rates were 78.3% (95%CI = 53.6-92.5) and 95.7% (95%CI = 78.1-99.9), respectively. After a median follow-up of 24.2 months, median progression-free survival (PFS) was 14.8 months (95% CI = 9.5-20.1) and median overall survival (OS) 26.9 months (95% CI = 23.0-30.8). Among the 21 patients completing the immunization phase, PFS was 17.5 months (95% CI = 12.0-23.0) and OS 26.9 months (95% CI = 24.6-NR). At the end of the immunization phase, all 21 patients showed high serum titers of anti-EGF antibodies, while EGF levels had decreased significantly. Finally, treatment with fully immunized patient's sera inhibited the EGFR pathway in tumor cells growing in vitro.
Conclusions:
Combination treatment with an anti-EGF vaccine is well tolerated; induces a sustained immunogenic effect and might enhance the clinical efficacy of EGFR TKIs.
Insights
This study shows that combining an anti-epidermal growth factor (EGF) vaccine with afatinib is safe and effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations. The combination demonstrated promising anti-tumor activity and improved survival outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Standard treatments like tyrosine kinase inhibitors (TKIs) combined with other therapies show limited success in EGFR-mutant NSCLC.
- New combination strategies are essential for improving patient outcomes in this population.
Purpose of the Study:
- To evaluate the safety, tolerability, and anti-tumor activity of first-line afatinib combined with an anti-EGF vaccine in advanced EGFR-mutant NSCLC patients.
- To assess the immunogenic effects and clinical efficacy of this novel combination therapy.
Main Methods:
- A single-arm, phase 1b study (EPICAL) enrolled 23 patients with advanced EGFR-mutant NSCLC.
- Patients received first-line afatinib combined with an anti-EGF vaccine.
- EGFR status, mutations, and serum biomarkers were analyzed using RT-PCR, ELISA, and Western blotting.
Main Results:
- The combination therapy was well-tolerated with no serious adverse events related to the vaccine.
- Objective response rate was 78.3% and disease control rate was 95.7%.
- Median progression-free survival (PFS) was 14.8 months and median overall survival (OS) was 26.9 months. Patients completing immunization showed improved PFS (17.5 months) and OS (26.9 months).
- High anti-EGF antibody titers and decreased EGF levels were observed, with patient sera inhibiting the EGFR pathway in vitro.
Conclusions:
- Combination treatment with an anti-EGF vaccine and afatinib is safe and well-tolerated in EGFR-mutant NSCLC.
- The treatment induces a sustained immunogenic effect, leading to significant anti-tumor activity and improved survival.
- This combination approach holds potential for enhancing the clinical efficacy of EGFR TKIs in NSCLC treatment.
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