Afatinib plus osimertinib in the treatment of osimertinib-resistant non-small cell lung carcinoma: a phase I clinical trial.
BMC Cancer
; 23(1): 6, 2023 Jan 03.
Article
in En
| MEDLINE
| ID: mdl-36597021
ABSTRACT
BACKGROUND:
Conquering acquired resistance to osimertinib remains a major challenge in treating patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Thus, we aimed to determine the safety and efficacy of combination treatment with osimertinib and afatinib for patients with acquired resistance to osimertinib.METHODS:
This open-label phase I study was a feasibility study of the combination of afatinib and osimertinib for patients with advanced EGFR-positive NSCLC who had progressive disease after receiving osimertinib. The primary endpoint was to determine the maximum tolerated dose (MTD). We enrolled patients who received afatinib at three different dose levels (level 1, 20 mg; level 2, 30 mg; level 3, 40 mg) combined with osimertinib at a standard dose of 80 mg once per day.RESULTS:
Thirteen patients were enrolled in this study. The MTD was defined as 30 mg afatinib when combined with daily oral administration of osimertinib (80 mg). The most frequent adverse events were diarrhea (76.9%), anemia (76.9%), and rash (69.2%). Considering the toxicity profiles during all treatment periods, the recommended oral dose of afatinib was determined as 20 mg daily, with an osimertinib dose of 80 mg. For all evaluable patients (n = 12), the response rate was 7.7% and the disease-control rate was 46.2%.CONCLUSION:
Combination therapy with osimertinib and afatinib was tolerable; however, the synergistic effect of afatinib with osimertinib may be limited in osimertinib-resistant patients. TRIAL REGISTRATION Japan Registry of Clinical Trials ID jRCTs051180008, registered date 08/11/2018.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Antineoplastic Combined Chemotherapy Protocols
/
Carcinoma, Non-Small-Cell Lung
/
Lung Neoplasms
Type of study:
Clinical_trials
Limits:
Humans
Language:
En
Journal:
BMC Cancer
Journal subject:
NEOPLASIAS
Year:
2023
Type:
Article
Affiliation country:
Japan