Lessons learned: Panitumumab shows activity in terms of disease control rate and preventing disease progression but not for tumor shrinkage in head and neck squamous cell cancer for second-line treatment. Epidermal growth factor receptor (EGFR) copy number gain, a property of tumor cells that theoretically could identify patients more likely to experience disease response, was common among patients having disease control.Our trial, given the lower toxicity with an every-2-week schedule, provides guidance for future trials, for example, in combinations of immune therapies and anti-EGFR-antibodies.
Background: The objective of this study was to investigate the efficacy and safety of panitumumab (anti-epidermal growth factor receptor [EGFR] antibody) given as a single agent in platinum-pretreated head and neck squamous cell cancer (HNSCC).
Methods: Patients with advanced HNSCC previously treated with platinum-containing therapy were included. Panitumumab was administered intravenously every 2 weeks at a dose of 6 mg/kg. Primary endpoint was overall response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; secondary endpoints were progression-free survival (PFS) and safety. A Simon's two-step design was chosen; 4 partial remissions (PR) in the first 32 patients were required for continuing to step two. An exploratory biomarker analysis was performed.
Results: Thirty-three patients were enrolled. Two patients obtained a PR for an ORR of 6%, and 15 (45%) showed stable disease (SD) for at least 2 months, resulting in a 51% disease control rate. Median PFS was 2.6 months (95% confidence interval [CI]: 1.7-3.7), while median OS was 9.7 months (95% CI: 6.3-17.2). The most frequent adverse drug reactions were cutaneous rash (64%) and hypomagnesemia (55%). Overall, 30% of patients experienced grade 3/4 adverse events. No infusion-related reactions occurred. EGFR copy number gain (CNG) was more frequent in patients who benefitted from panitumumab. Two uncommon KRAS mutations (G48E, T50I) and 3 canonical PIK3CA mutations (all E545K) were detected. High-risk HPV16 was found in 10 patients and EGFR CNG in 13 treated patients. EGFR CNG seems to be more frequent in individuals with at least SD compared with patients with progressive disease (59% vs. 30%). PFS for patients with EGFR CNG was 4.6 months (95% CI: 1.0-9.2 months) and 1.9 months (95% CI: 1.0-3.2 months) for patients without CNG (p = .02).
Conclusion: Panitumumab monotherapy in pretreated HNSCC patients was well tolerated but moderately active. We observed a considerable disease control rate. Future strategies with this agent comprise right patient selection through the identification of reliable biomarkers and gene signatures predicting response and, considering good tolerability and convenience, combination strategies with novel agents and immune therapeutic agents.
经验总结
• 帕尼单抗在疾病控制率和预防疾病进展方面表现出活性, 但在用于二线治疗头颈鳞状细胞癌时没有表现出使肿瘤缩小的活性。表皮生长因子受体（EGFR）拷贝数增加, 理论上能够识别出更可能达到疾病缓解的患者的肿瘤细胞特性, 在疾病得到控制的患者中较常见。
• 考虑到每2周一次给药的毒性较低, 我们的试验为未来的试验提供了指导, 例如免疫治疗和抗EGFR抗体的组合。
摘要
背景.本研究的目的是研究在铂类药物预处理的头颈鳞状细胞癌（HNSCC）患者中帕尼单抗[抗表皮生长因子受体（EGFR）抗体]作为单一药物给药的疗效和安全性。
方法.纳入既往接受过含铂药物治疗的晚期HNSCC患者。以6 mg/kg剂量每2周进行一次帕尼单抗静脉给药。根据1.1版实体肿瘤反应评估标准（RECIST）, 主要终点为总缓解率（ORR）；次要终点是无进展生存期（PFS）和安全性。选择Simon的两阶段设计；只有前32例患者中有4例部分缓解（PR）, 患者才能继续参与第2阶段研究。进行了探索性生物标志物分析。
结果.入组了33例患者。两例患者获得了PR, ORR为6%, 15例患者（45%）疾病稳定至少2个月, 疾病控制率达到51％。中位PFS是2.6个月[95％置信区间（CI）：1.7‐3.7], 而中位OS为9.7个月（95％CI为6.3‐17.2）。最常见的药物不良反应为皮疹（64％）和低镁血症（55％）。总体上, 30％的患者经历了3级/4级不良事件。没有发生与输注有关的反应。EGFR拷贝数增加（CNG）在受益于帕尼单抗的患者中较常见。检测到两种罕见的KRAS突变（G48E, T50I）和三种典型的PIK3CA突变（均为E545K）。在10例患者中发现高危HPV16, 在13例接收治疗的患者中发现EGFR CNG。与进行性疾病患者相比, 在至少达到SD的患者个体中EGFR CNG似乎更常见（59％vs. 30 ％）, EGFR CNG患者的PFS为4.6个月（95％CI：1.0‐9.2个月）, 无CNG患者的PFS为1.9个月（95％CI：1.0‐3.2个月）（p = 0.02）。
结论.在预处理的HNSCC患者中帕尼单抗单药治疗耐受性良好, 但活性中等。我们观察到相当高的疾病控制率。该药物的未来用药策略包括通过识别预测反应的可靠生物标志物和基因标记选择合适的患者, 考虑良好的耐受性和便利性, 组合使用新型药物和免疫治疗制剂。
Trial registration: ClinicalTrials.gov NCT02643056.
© AlphaMedPress; the data published online to support this summary is the property of the authors.