Phase II Study of Low-Dose Afatinib Maintenance Treatment Among Patients with EGFR-Mutated Non-Small Cell Lung Cancer: North Japan Lung Cancer Study Group Trial 1601 (NJLCG1601)

Lung Cancer
19/06/2020

Nakamura A, et al. Oncologist 2020.

ABSTRACT

TRIAL INFORMATION: ClinicalTrials.gov Identifier: UMIN 000020688 [EMBED URL: httpss://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000020688] Sponsor: North Japan Lung Cancer Study Group Principal Investigator: Atsushi Nakamura IRB Approved: Yes LESSONS LEARNED: Low-dose afatinib maintenance treatment among patients with EGFR-mutated NSCLC allowed for treatment continuation for longer with fewer treatment-related AEs without detracting from the therapeutic efficacy. This modified regimen represents a practical usage that balances effectiveness and safety.

BACKGROUND: Although afatinib is an effective therapy for patients with EGFR-mutated non-small cell lung cancer (NSCLC), drug-related adverse events (AEs) have often necessitated dose reductions. In a post hoc analysis of the LUX-Lung 3 and 6 trials, there was no difference in median progression-free survival (PFS) between patients who had the dose of afatinib reduced and those who did not. We thus evaluated the efficacy and tolerability of low-dose afatinib maintenance treatment among patients with NSCLC harboring EGFR mutations who had not been previously treated.

METHODS: Eligible patients received afatinib 40 mg orally once daily. When prescribed grade ≥ 2 AEs, rash of grade ≥ 3, or unacceptable toxicity occurred, the afatinib dose was reduced from 40 to 30 mg and if needed from 30 to 20 mg. The primary endpoint was the 1-year PFS rate. Secondary endpoints were PFS, overall response rate (ORR), and toxicity.

RESULTS: Among 30 patients, 93% had adenocarcinoma, 53% had exon 19 deletion, 37% had L858R, and 10% had minor mutations. The 1-year PFS rate was 50% (95% confidence interval [CI], 31.3-66.1) and the median PFS was 11.8 months (95% CI, 7.1-21.4). The incidence rate of grade ≥ 3 toxicities was 57%, including elevated aspartate aminotransferase/alanine aminotransferase level (13%), diarrhea (10%), and paronychia (10%).

CONCLUSION: Low-dose afatinib maintenance treatment reduced treatment-related AEs without detracting from the therapeutic efficacy.