在1%-2%的非小细胞肺癌(NSCLC)患者中发现HER2外显子20插入和点突变是致癌驱动因素。没有针对这类患者的靶向治疗被批准。我们前瞻性地评估了两种抗人表皮生长因子2抗体(HER2 [HER2]曲妥珠单抗和帕妥珠单抗联合多西他赛;曲妥珠单抗和帕妥珠单抗)和多西他赛。

在1%-2%的非小细胞肺癌(NSCLC)患者中发现HER2外显子20插入和点突变是致癌驱动因素。没有针对这类患者的靶向治疗被批准。我们前瞻性地评估了两种抗人表皮生长因子2抗体(HER2 [HER2]曲妥珠单抗和帕妥珠单抗联合多西他赛;曲妥珠单抗和帕妥珠单抗)和多西他赛。

45例患者入选并接受治疗。中位年龄为64.5岁(范围为31-84岁)，35%为吸烟者，72%为女性，15%的东部肿瘤合作组表现状态为2,30%有脑转移。客观有效率为29% (n = 13)， 58%的患者病情稳定(n = 26)。中位无进展生存期为6.8个月(95% CI 4.0 ~ 8.5)。确认有应答的患者(n = 13)应答的中位持续时间为11个月(95% CI, 2.9 - 14.9)。64%的患者观察到3/4级治疗相关不良事件。无患者因毒性而停止治疗。最常见的3级治疗相关不良事件是中性粒细胞减少症(33%)、腹泻(13%)和贫血(9%)。曲妥珠单抗、帕妥珠单抗和多西他赛三联疗法对her2突变预处理的晚期NSCLC是可行和有效的。这些结果强调了基于HER2抗体的策略的有效性，应该考虑这些患者。

Abstract

Purpose: HER2 exon 20 insertions and point mutations are oncogenic drivers found in 1%-2% of patients with non-small-cell lung cancer (NSCLC). No targeted therapy is approved for this subset of patients. We prospectively evaluated the effectiveness of the combination of two antibodies against human epidermal growth factor 2 (HER2 [HER2] trastuzumab and pertuzumab with docetaxel; trastuzumab and pertuzumab) and docetaxel.

Methods: The IFCT 1703-R2D2 trial is a multicenter, nonrandomized phase II study. Patients with HER2-mutated, advanced NSCLC who progressed after ≥ 1 platinum-based treatment were enrolled. Patients received pertuzumab at a loading dose of 840 mg and 420 mg thereafter; trastuzumab at an 8 mg/kg loading dose and 6 mg/kg thereafter; and docetaxel at a dose of 75 mg/m2 every 3 weeks. The primary outcome was the objective response rate (ORR). Other end points included the duration of response, progression-free survival, and safety (NCT03845270).

Results: Forty-five patients were enrolled and treated. The median age was 64.5 years (range, 31-84 years), 35% were smokers, 72% were females, 15% had an Eastern Cooperative Oncology Group performance status of 2, and 30% had brain metastases. The objective response rate was 29% (n = 13), and 58% had stable disease (n = 26). The median progression-free survival was 6.8 months (95% CI, 4.0 to 8.5). The median duration of response in patients with a confirmed response (n = 13) was 11 months (95% CI, 2.9 to 14.9). Grade 3/4 treatment-related adverse events were observed in 64% of the patients. No patient discontinued treatment because of toxicity. The most frequent grade ≥ 3 treatment-related adverse events were neutropenia (33%), diarrhea (13%), and anemia (9%).

Conclusion: Triple therapy with trastuzumab, pertuzumab, and docetaxel is feasible and effective for HER2-mutated pretreated advanced NSCLC. These results highlight the effectiveness of the HER2 antibody-based strategy, which should be considered for these patients.

原文链接

pubmed.ncbi.nlm.nih.gov/35073148/

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