FGFR 1-3抑制剂治疗FGFR1扩增的肺鳞癌:有效率3/21,控制率10/21
  • FGFR 1-3抑制剂BGJ398的一期研究表明,剂量≥ 100mg时,MR=11%,为确定潜在耐药机制,对患者肿瘤组织继续进行检测分析;
  • 21例sqNSCLC患者接受治疗(≥ 100mg):3例PR、7例SD、7例PD;
  • 对9例患者进行CAGE分析(3例PR、2例SD、2例PD、2例死亡):均发现TP53基因突变;
  • 2例CDKN2A基因突变,3例MLL2基因突变,2例典型和1例非典型PIK3CA突变;
  • BGJ398治疗的FGFR1扩增患者中,MLL2突变和PIK3CA突变似乎起了负面作用,这需进行更多数据分析。

Fibroblast kinase 1-3 inhibitor BGJ398 in patients with FGFR1 amplified squamous non-small cell lung cancer treated in a phase I study: Evaluation of tumor tissue and response at a single center

FGFR 1-3抑制剂BGJ398治疗FGFR1扩增的鳞状非小细胞肺癌患者一期临床实验:肿瘤组织和单一中心评估


Abstract & Authors:展开

Background: Fibroblast growth factor receptor 1 (FGFR1) amplification in squamous cell non-small cell lung cancer (sqNSCLC) has been described as potential oncogenic and targetable driver in cell lines and murine models. However, a phase I study evaluating FGFR 1-3 inhibitor BGJ398 showed moderate response rate of 11% in FGFR1amplified sgNSCLC treated with dose ≥ 100mg. To identify underlying mechanisms of resistance, we analyzed tumor tissues of selected patients.
Methods: Within the phase I BGJ398 study, patients (pts) with FGFR1amplified sqNSCLC were treated orally with escalating dose (5 to 150mg) of BGJ398 once daily (QD) or 50mg twice a day. In the expansion phase, pts received BGJ398 either continuously QD or on a 3-weeks on/1-week off schedule. CT scans for response were performed every 8 weeks. Available tumor tissue of pts treated with BGJ398 at our center was analyzed using hybrid capture–based massively parallel sequencing (CAGE).
Results: Twenty-one pts with FGFR1 amplified sqNSCLC were treated with ≥ 100mg BGJ398 at our site. As best response, 3 pts showed partial response (PR), 7 pts stable disease (SD) and 7 pts progressive disease (PD). Two pts withdrew their consents and 2 pts died ahead of first CT scan: one due to infection and one due to sudden death. We performed CAGE covering 256 genes on 9 patients: on 3 pts with PR, 2 pts with SD, 2 pts with PD and 2 pts who died before first CT scan. All analyzed patients harbored mutations in TP53. Additionally, we detected two CDKN2A (one patient with PR and one patient who died before first CT) and three MLL2 stop codon and frame shift mutations (two patients with SD and one patient with PD). Of interest, we identified three patients with two canonical (one patient with SD and one patient who died before first CT) and one non-canonical mutations in PIK3CA(one patient with SD).
Conclusions: In our analysis, MLL2 and PIK3CA mutations seem to have a negative impact on response in FGFR1 amplified pts treated with BGJ398. Further analysis with higher patient number is needed to identify the role of MLL2 and PIK3CA mutations in FGFR1 amplified sqNSCLC.

All Authors:
Lucia Nogova