Rebiopsy Enhances Survival with Afatinib vs. Osimertinib in EGFR Exon 19 Deletion Non-Small Cell Lung Cancer: A Multicenter Study in Taiwan

Abstract

Background: Afatinib and Osimertinib are first-line treatments for EGFR-mutated advanced non-small cell lung cancer (NSCLC), but their comparative efficacies and the patient groups that benefit the most remain unclear. This multicenter retrospective study evaluated the efficacy of first-line Afatinib and Osimertinib in NSCLC patients with EGFR 19del and no brain metastases at diagnosis.

Methods: The primary endpoints were time on treatment (ToT) and overall survival (OS). Survival analyses were performed for three groups: Afatinib followed by Osimertinib, Afatinib followed by other therapies, and Osimertinib (alone or followed by other therapies). Rebiopsy practices, including T790M mutation detection, were also analyzed in patients with disease progression on Afatinib.

Results: Among 97 Afatinib-treated and 60 Osimertinib-treated patients, Osimertinib showed a significantly longer ToT (23.3 vs. 16.5 months; p = 0.007). Median OS was numerically higher for Afatinib with sequential Osimertinib (40.5 vs. 34.6 months for Osimertinib; p = 0.473). Osimertinib demonstrated advantages, with fewer brain metastases upon progression and fewer adverse effects. In the Afatinib group, 64% of patients with disease progression underwent rebiopsy, with 39% testing positive for T790M mutation and subsequently receiving Osimertinib. Rebiopsy was most frequently performed on the lung parenchyma using non-surgical methods.

Conclusions: In this real-world study, Osimertinib achieved a significantly longer ToT compared to Afatinib in NSCLC patients with EGFR 19del and no brain metastases. The sequential use of Afatinib followed by Osimertinib showed a trend toward improved OS, highlighting the importance of rebiopsy for identifying T790M mutations to guide subsequent therapy.

Keywords: Afatinib; EGFR mutation; Osimertinib; lung cancer; rebiopsy.

Figure 1

Kaplan–Meier survival curves for time on treatment (TOT) and overall survival (OS). (A) The median time on treatment (TOT) in the Afatinib cohort was 16.7 months (interquartile range [IQR], 7.9–30.0), significantly shorter than in the Osimertinib cohort, where it was 23.8 months (IQR,13.4–not reached) (hazard ratio for discontinuation of first-line [1 L] treatment, 0.61 (98% CI: 0.49–0.72); Log-rank p = 0.007). (B) However, while the OS in the Afatinib group appeared higher at 40.5 months (IQR, 25.4–63.6) compared to the 34.6 months (IQR, 22.7–not reached) in the Osimertinib group, this difference was not statistically significant (hazard ratio for death, 1.17 (98% CI: 0.75–1.85); Log-rank p = 0.473).

Figure 2

Comparative Kaplan–Meier analysis of overall survival (OS) across three distinct treatment groups. The Kaplan–Meier curve analysis was conducted to evaluate overall survival (OS) across three distinct groups. Upon subdividing the Afatinib group into two categories, it was noted that the subgroup receiving first-line [1 L] Afatinib followed by second-line [2 L] Osimertinib exhibited a promising trend, with a median OS of 49.4 months (green dashed line), surpassing both the 1 L Afatinib followed by 2 L chemotherapy or other treatment subgroup (blue short-dashed line; median OS: 35.5 months) and the first-line Osimertinib subgroup (red line; median OS: 34.6 months). The differences among the three groups were not statistically significant (Log-rank p = 0.055).

Figure 3

Flow diagram of patients with/without rebiopsy in first-line Afatinib group. In the Afatinib cohort, 69 out of 97 patients experienced disease progression during first-line treatment after excluding those who were lost to follow-up, deceased, or discontinued their use due to intolerable side effects. Among these, 64% (44 patients) underwent rebiopsy, revealing 17 cases with confirmed acquisition of the T790M mutation. Subsequently, all identified patients received Osimertinib.

Figure 4

Biopsy methods/sample sites/types of gene alteration examination among the 44 patients receiving rebiopsy for detection of acquired T790M mutation. Upon a detailed analysis of cases undergoing rebiopsy, non-surgical methods were found to predominate. These included bronchoscopic biopsy, ultrasound-guided biopsy, CT-guided biopsy, and pleural effusion drainage. The most frequently targeted sites for rebiopsy were the lung parenchyma, intrapulmonary lymph nodes, and bronchial trees. MALDI-TOF MS, Matrix-Assisted Laser Desorption Ionization–Time-of-Flight Mass Spectrometry; NGS, next-generation sequencing. * Metastatic sites: bladder tumor, right neck mass, right subphrenic tumor, pleural tumor; † both are small cell transformations.